Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyG K Kanatbekova, O A Bolbachan, D D Ibraimova
The article presents results of analysis of medical demographic indicators of the Kyrgyz Republic in 2016-2024. The study was carried out concerning dynamics of population size, natality, mortality and migration processes based on statistical data from the National Statistical Committee and the Center of E-Health Care. The regional differences in demographic trends were revealed. The high natality is specific for Southern regions, while in Northern regions its steady decreasing was fixed. It is established that COVID-19 pandemic had short-term impact on mortality growth in 2020. Despite positive natural increase, its pace is decreasing that requires elaboration of state demographic policy and mechanisms stimulating natality, population health promotion and development of regional health care infrastructure. In 2022-2023 migration flows demonstrated positive balance that reflects changes in social economic priorities of population. The main motives for migration remain low wages, limited career opportunities and uncertainty about future. The obtained results confirm necessity of systematic approach to prognostication of demographic processes and development of measures stabilizing medical demographic situation in the Republic.
Pakistan journal of pharmaceutical sciencesZaishuang Ju, Yutong Wu, Lili Tian, Dachuan Shen, Ruoyu Wang
BACKGROUND: Patients with lung adenocarcinoma (LUAD) receiving radiotherapy represent an important but underexplored clinical subgroup. These patients often undergo concomitant pharmacologic treatments, yet the prognostic impact and underlying determinants of such combined regimens remain poorly understood. OBJECTIVE: This retrospective observational study aimed to develop and validate a radiotherapy-specific machine learning prognostic model for LUAD and to compare survival across concomitant pharmacologic regimens. METHODS: In this retrospective observational study, using genomic and clinical data from TCGA, a radiotherapy-specific prognostic model for LUAD was developed and validated through ten machine learning algorithms. Survival analyses were conducted across distinct concomitant pharmacologic strategies, followed by functional enrichment to elucidate molecular mechanisms underlying differential outcomes. RESULTS: Demonstrating robust prognostic abilities, the model efficiently sorted patients into high- and low-risk categories. Both treatment type and risk score independently predicted overall survival, with significant interaction effects. Low-risk patients receiving targeted or combination therapy-mainly erlotinib, gefitinib, or bevacizumab-exhibited substantially improved survival compared with those receiving conventional chemotherapy. Enrichment of "Exogenous peptide presentation," "MHC class II assembly," "Peptide-MHC II assembly," and "Symbiotic interaction" pathways indicated immune modulation and host-tumor crosstalk as key mediators of treatment efficacy. CONCLUSION: This study establishes a radiotherapy-specific prognostic model for lung adenocarcinoma, demonstrating distinct molecular and therapeutic heterogeneity and highlighting the superior survival benefit of targeted combination therapy in low-risk patients.
Pakistan journal of pharmaceutical sciencesZhen Han, Qian Zhang, Bo Cai, Rui Zhou, Tao Zhang, Jian Wan
BACKGROUND: Sepsis-induced acute lung injury (ALI) is a critical illness with a high mortality rate. Madecassic acid (MA), a pentacyclic triterpenoid extracted from Centella asiatica, exhibits multiple biological activities, but its role in sepsis-associated ALI remains poorly elucidated. OBJECTIVES: The aim of this study was to investigate the protective effect of MA on lipopolysaccharide (LPS)-induced ALI in mice and to elucidate its potential mechanisms in regulating inflammation, oxidative stress, apoptosis and the PI3K/AKT/mTOR signaling pathway. METHODS: An ALI mouse model was established by intraperitoneal LPS injection. The mice were randomly divided into a sham operation group, an MA alone group, an LPS model group and an LPS combined with MA treatment group. The degree of lung injury was assessed via histopathological examination of the lungs and the lung wet/dry weight ratio; the levels of inflammatory factors (TNF-α and IL-6) and oxidative stress markers (MPO, MDA, SOD and GSH-Px) in the bronchoalveolar lavage fluid (BALF) were measured; and the expression of apoptosis-related proteins and PI3K/AKT/mTOR pathway activation in the lung tissues were detected via Western blotting. RESULTS: MA treatment significantly reduced LPS-induced lung tissue injury, edema and inflammatory cell infiltration; decreased the levels of proinflammatory factors (TNF-α and IL-6); improved oxidative stress parameters (decreased MPO and MDA levels and increased SOD and GSH-Px levels); inhibited apoptosis (downregulated Bax and cleaved caspase-3 expression and upregulated Bcl-2 expression); and inhibited the phosphorylation of PI3K, AKT and mTOR. CONCLUSION: MA attenuates sepsis-associated ALI through anti-inflammatory, antioxidant and anti-apoptotic effects and this mechanism is related to inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. MA has the potential to be a therapeutic agent for sepsis-associated ALI.
International journal of psychology : Journal international de psychologieQiandong Wang, Yawen Li, Yuxuan Liang, Sio Pan Hoi, Li Yi
Individuals from regions affected by infectious disease outbreaks may be stigmatized because others hold negative mental images-or mental representations-of them. This study investigated whether such outbreaks lead to the formation of negative mental representations of residents in affected areas and explored the role of disease severity in this process. Study 1 revealed that during the early stages of the COVID-19 epidemic, the public's mental representations of residents from Wuhan were perceived as less attractive than those of Chengdu residents and associated with disgust and behavioural avoidance. However, differences disappeared after the restrictions of the epidemic were lifted. The results indicate that the COVID-19 outbreak triggered stigmatization of residents in Wuhan. In Study 2, disease severity and perceived threat were manipulated, and results show that participants formed less attractive face representations of residents from areas where severe infectious diseases broke out than those from areas affected by mild infectious diseases. This proved that the severity of infectious diseases affected the extent of stigmatization towards residents in outbreak areas. These results further our understanding of the mechanisms and factors underlying stigmatization associated with affected regions and may inform effective public health strategies to mitigate stigma and support disease control efforts.
Pakistan journal of pharmaceutical sciencesJiajia Ying
BACKGROUND: Given the high incidence of apnea of prematurity (AOP) and the repeated hypoxia-induced nerve damage, treatment optimization from the dosing perspective is critical. Caffeine is the current first-line therapeutic drug for AOP. However, the conventional dose results in low blood concentration compliance, with significant variation among individuals. OBJECTIVES: To explore the clinical efficacy and safety of a therapeutic drug monitoring (TDM)-guided individualized caffeine dosage regimen and its association with early neurobehavioral development and weight gain in preterm infants (PTIs). METHODS: In this retrospective propensity score-matched cohort study, 130 PTIs with AOP were included after 1:1 matching, with 65 infants in the TDM-guided individualized dosing group and 65 in the conventional fixed-dose group. Inter-group comparative assessments were conducted from the perspectives of blood drug concentration compliance rates, apnea control, adverse reactions, neurobehavioral development scores, clinical outcomes and weight gain rates. RESULTS: Compared with the conventional fixed-dose group, the TDM-guided individualized dosing group had a significantly higher target attainment rate of blood caffeine concentration (92.31% vs 70.77%; OR=5.22, 95% CI 1.68-12.74, P=0.002), lower apnea episode frequency at 4 weeks (MD -1.40 times/day, 95% CI -2.13 to -0.67, P<0.001), lower overall incidence of adverse reactions (6.15% vs 20.00%; OR=0.26, 95% CI 0.09-0.87, P=0.035), higher NBNA score at 40 weeks of corrected gestational age (MD 1.74, 95% CI 1.23-2.25, P<0.001), shorter hospital stay (MD -4.11 days, 95% CI -6.51 to -1.71, P=0.001) and faster weight gain rate (MD 7.88 g/day, 95% CI 3.21-12.55, P=0.001). CONCLUSION: The TDM-guided individualized caffeine dosing regimen was associated with improved precision of AOP treatment, better short-term therapeutic efficacy and safety, and higher early neurobehavioral assessment scores and weight gain in preterm infants within 6 months of corrected gestational age. Multicenter studies with longer follow-up are needed to further verify its long-term clinical benefits.
PulmonologyCristina Aljama, Ane Lopez-Gonzalez, Hanan Tanash, Maria Torres-Duran, Alice M Turner, Carlota Rodriguez-Garcia, Angelo Guido Corsico, Catarina Guimarães, José…
BACKGROUND: Data on health utilities in Alpha-1 antitrypsin deficiency (AATD) are scarce. This study aimed to evaluate health-related quality of life (HRQoL) using the EQ-5D in a cohort of AATD Pi*ZZ individuals from the European AATD Research Collaboration (EARCO) registry and to identify factors associated with impaired health utilities. METHODS: Observational, cross-sectional, multicenter study including AATD patients with Pi*ZZ genotype enrolled up to April 2025. HRQoL was assessed using the EQ-5D questionnaire (index and visual analogue scale (VAS)). Sociodemographic data, smoking history, respiratory symptoms, comorbidities, lung function and exacerbations were collected. Multivariable generalised linear models were used to identify factors independently associated with EQ-5D index scores in the overall population and in patients with AATD-COPD. RESULTS: A total of 1710 Pi*ZZ individuals were analysed with a mean age 55.2 ± 13.8 years, 51% were male and 49.6% had COPD. Mean EQ-5D index and VAS were 0.82 ± 0.22 and 62.9 ± 25.9, respectively. Patients with COPD had significantly worse EQ-5D index (0.75 ± 0.24 vs 0.90 ± 0.16) and VAS scores (56.3 ± 24.4 vs 70.4 ± 26.8; both p < 0.001). In multivariable analyses, higher symptom burden (CAT, mMRC), long-term oxygen therapy, being unemployed, exacerbations, COPD, bronchiectasis and lower educational level were independently associated with worse EQ-5D scores in Pi*ZZ subjects. CONCLUSIONS: HRQoL was substantially impaired in Pi*ZZ individuals, particularly in those with COPD. Symptom burden and exacerbations were stronger determinants of EQ-5D than lung function alone in all Pi*ZZ patients. Patients with AATD-associated COPD exhibited an HRQoL impairment comparable to that observed in usual COPD populations, but at a younger age.
BACKGROUND: In patients with COPD, exacerbations mark disease progression, with significant reduction in quality of life and impact on mortality. Early detection is crucial to mitigate their consequences. The aim of this study was to investigate whether monitoring symptoms and exercise endurance at each pulmonary rehabilitation maintenance session could predict severe exacerbations of COPD. STUDY DESIGN AND METHODS: Prospective multicentre study including 128 stable COPD patients in maintenance pulmonary rehabilitation programmes, in 21 French rehabilitation centres (NCT05492149). At each session, symptoms with COPD Assessment Test (CAT), perceived dyspnoea (mBorg scale) and endurance exercise performance (in MET.minutes) were recorded. We evaluated whether these parameters could predict severe exacerbations using baseline and lagged logistic regression models, and explored temporal relationships with cross-lagged correlation analyses. RESULTS: Over one year and 4,200 recorded sessions (33 ± 25 per patient), 19 out of 128 participants experienced a severe exacerbation (a prevalence of 14.8%). Prediction models using isolated clinical markers such as CAT, mBorg or performance showed limited predictive accuracy (AUCs 0.45-0.58; all p > 0.1). Cross-lagged analyses revealed weak, short-term associations between symptoms (CAT score), perceived dyspnoea (mBorg scale) and exercise performance. CONCLUSION: This study showed that nearly 15% of patients with COPD included in a maintenance rehabilitation programme experienced severe exacerbations during long-term follow-up. In this real-world maintenance pulmonary rehabilitation setting, routine clinical and isolated exercise data were insufficient to reliably predict severe COPD exacerbations. These findings highlight the complexity of severe exacerbations in COPD and emphasise the importance of developing more integrated research and digital monitoring strategies, using multimodal approaches that combine physiological, biological, behavioural, and environmental data.
Annals of medicineKirsty E Krieg, Annemarie L Lee, Marita J Dale, Tiffany J Dwyer, Zoe J McKeough
INTRODUCTION: The treatable traits approach involves the identification of traits that are measurable and clinically relevant to the patient, which informs an individualized management plan. While improved quality of life and health outcomes have been demonstrated, the acceptability of this approach to people with bronchiectasis has not been explored. The aim of our study was to explore the acceptability of the treatable traits approach to people with bronchiectasis in a regional setting. PATIENTS AND METHODS: An exploratory qualitative study. Interviews were conducted with adults who first attended an outpatient bronchiectasis clinic in regional Australia, which had implemented the treatable traits approach. The interview guide was developed to explore the seven components of the theoretical framework of acceptability. Engagement with the transcripts occurred using the six phases of thematic analysis to develop key themes. RESULTS: Ten participants were included (age 37-82 years; female sex, 70%; Bronchiectasis Severity Index, mild, 20%; moderate, 50%; and severe, 30%). This study reports three themes. 'A tool kit to support my health' explores the contribution of individualized and multifaceted interventions to a perceived improvement in respiratory health. 'Better health, better self' captures the patient-reported impact of improved respiratory health on quality of life. 'Some things don't change' describes the ongoing challenges for people living with bronchiectasis that are not impacted by the clinic interventions. CONCLUSION: People with bronchiectasis from a single regional Australian clinic described a highly valued and acceptable clinic experience, with perceived improvements in respiratory health and overall well-being despite significant ongoing impacts on daily life. CLINICAL TRIAL REGISTRATION: This study was registered in the Australian and New Zealand Clinical Trials Registry (https://www.anzctr.org.au/, ACTRN12620000377932).
Human vaccines & immunotherapeuticsSophie Grice, Joshua Gardner, Paul Thomson, Luisa Hering, Lonnie MacDonald, Stacey Collins, Lance Turtle, Daniel F Carr, Anna Olsson-Brown, Sean Hammond, Dean …
An extensive body of clinical and experimental evidence demonstrates that immune checkpoint blockade can invigorate recall immune responses. This phenomenon has previously been highlighted using ex vivo (healthy donor) and in vivo (immunotherapy patients) models of immune checkpoint inhibitor (ICI) administration that demonstrate an enhancement of the T-cell response to concomitant small-molecule drugs. However, the immunological and clinical impact of ICI therapy pre-ceding vaccination, where robust antigen-specific immunogenicity is essential, remains poorly defined. In this study, we utilized an ex vivo assay to evaluate lymphocyte recall responses within peripheral blood mononuclear cells (PBMC) derived from healthy donors and patients pre- and post-immunotherapy following exposure to SARS-CoV-2 derived peptides and ChAdOx1 nCoV-19. In line with the anticipated effects of the primary pharmacology of immune checkpoint inhibitors, we outline an acute increase in proliferation and cytokine and cytolytic molecule secretion following immune checkpoint blockade in response to CEF(T), wild-type SARS-CoV-2 spike pools 1 and 2, and ChAdOx1 nCoV-19. Future studies are needed to evaluate the clinical correlates of the veracity of such responses with protection and incidence of adverse events.
Annals of medicineYang Xie, Peng Zhang, Jiajia Wang, Tao Chen, Jiansheng Li
BACKGROUND: Patient-reported outcomes (PROs) have become essential endpoints in clinical trials for bronchiectasis. However, no validated PRO instrument currently exists for the Chinese population. This study aimed to develop and validate a disease-specific Patient-Reported Outcome scale for Bronchiectasis (BE-PRO) tailored to Chinese patients. METHODS: A mixed-methods approach was used to develop the BE-PRO. The conceptual framework and initial item pool were developed primarily from semi-structured patient interviews and supplemented by literature and existing-instrument reviews and medical-record analysis. Items were refined through qualitative review by experts and patients. Two field surveys were then conducted, with items selected using classical test theory (CTT), item response theory (IRT), and structural equation modeling (SEM). Finally, a formal validation survey assessed the psychometric properties of the BE-PRO. RESULTS: The final BE-PRO consists of 16 items organized into five domains: physiology, psychology, environment, society, and treatment satisfaction. The scale demonstrated excellent internal consistency (Cronbach's α = 0.912), split-half reliability (0.856) and satisfactory structural validity (CFI = 0.961; RMSEA = 0.068). Strong correlations with the SF-36 and QOL-B supported criterion validity, while moderate correlations with the BSI and E-FACED supported its clinical relevance. The scale showed high feasibility, with 100% response and completion rates and a mean completion time of 9.07 min. CONCLUSION: The 16-item BE-PRO is a reliable, psychometrically validated and feasible instrument for assessing patient-reported outcomes in Chinese patients with bronchiectasis. Its strong psychometric properties support its use in both clinical trials and routine practice.
Global health actionJanan J Dietrich, Tatiana E Pakhomova, C Andrew Basham, Kalysha Closson, Bongiwe Zulu, Julie Jesson, Campion Zharima, Mags Beksinska, Rishav Singh, Erica Dong,…
BACKGROUND: Understanding which factors impact vaccine uptake is important for supporting ongoing and future vaccine programmes among youth. OBJECTIVE: This study examined predictors of COVID-19 vaccination uptake among South African youth in the eThekwini District. METHODS: Cross-sectional data from an online survey (AYAZAZI RIGHTS: December 2021-May 2022) of youth aged 18-24 in the eThekwini district, South Africa, were analyzed using a gender-stratified logistic regression of vaccination status on candidate predictors of interest (k = 14). A full model with backwards selection using Akaike's Information Criterion was employed to remove predictors that did not add to the model's explanatory power. RESULTS: Of 1383 participants, 54% were women, with a median sample age of 21.8 years. Overall, 37.9% (n = 525) of participants had received a COVID-19 vaccine, 58.6% of whom were women. In this cross‑sectional, observational analysis, the most consistent predictors of vaccination status were older age, living with seniors in the home, and personal proximity to severe pandemic outcomes, specifically knowing people who had been hospitalized or died due to COVID-19. Gender‑specific predictors included ethnicity, having children for women, employment, and relationship status. CONCLUSION: Socio-demographic as well as community factors predicted receiving a COVID-19 vaccination, varying by gender. Better understanding of modifiable factors to support vaccine uptake, and curbing vaccine hesitancy related to mistrust and misinformation, will help support South Africa's immunization programs among youth, and can help inform targeted, inclusive, and equity-oriented public-health strategies.
European journal of psychotraumatologyShamini Satkunam, Irene Dimitriou, Madiha Shaikh
Background: Psychological morbidity is common following admission to adult intensive care units (ICUs), with many patients experiencing post-traumatic stress disorder (PTSD), anxiety, and depression as part of post-intensive care syndrome. Eye Movement Desensitisation and Reprocessing (EMDR) is an established trauma-focused psychological therapy; however, its evidence base within critical care populations remains emerging.Objectives: This scoping review aimed to map the extent, characteristics, and findings of the available literature on the use of EMDR for ICU-related psychological distress.Methods: A scoping review was conducted in accordance with Joanna Briggs Institute methodology and reported following the PRISMA-ScR guidelines. The review aimed to systematically identify and synthesise evidence relating to the application and reported outcomes of EMDR in ICU survivors.Results: Seven publications representing six independent study populations were included. Participants included adult ICU patients experiencing PTSD symptoms, delirium-related psychological disturbances, and COVID-19-related distress. EMDR was delivered using either standard protocols or the Recent Traumatic Episode Protocol (R-TEP). Across the evidence base, EMDR was associated with reductions in trauma-related distress, although evidence for improvements in anxiety and depression was less consistent. Where qualitative data were available, participants additionally reported improved integration and processing of ICU experiences. Overall, methodological heterogeneity, overlapping samples, small sample sizes, and limited controlled evidence restrict the strength of conclusions that can be drawn.Conclusions: This review highlights growing but preliminary evidence supporting the feasibility and potential utility of EMDR, including R-TEP, for ICU-related psychological distress. While findings are promising, the current evidence base remains insufficient to determine effectiveness. Future research should prioritise adequately powered controlled studies, standardised outcome measures, longer-term follow-up, and more diverse ICU populations to strengthen the evidence base and inform clinical implementation.
PulmonologyCíntia Dias, Raquel Marinho, José Joaquim Alvarelhão, Eduarda Tinoco, Tiago Alfaro, Vânia Fernandes, Sérgio Campainha, Chris Burtin, Alda Marques
BACKGROUND: Measurement properties of patient-reported outcome measures assessing functional performance and activity limitations in interstitial lung disease (ILD) are often unknown. RESEARCH QUESTION: To evaluate the reliability and validity of the Canadian Occupational Performance Measure (COPM) and the Pulmonary Functional Status and Dyspnea Questionnaire-Modified version (PFSDQ-M) in European Portuguese among people with ILD, and to explore differences between fibrotic and non-fibrotic ILD. STUDY DESIGN AND METHODS: Cross-sectional study. Internal consistency (Cronbach's α), test-retest/intra-rater and inter-rater reliability assessed using intraclass correlation coefficients [ICC2,1[95%CI]], standard error of measurement (SEM), minimal detectable change at 95% confidence level (MDC95) and Bland-Altman analysis, and floor/ceiling effects were evaluated. Construct validity was explored with correlations: convergent validity with the LCADL, CIS-8, 6MWT and 1-minSTS, only for PFSDQ-M; divergent validity with age and lung function for both instruments. Subgroup analyses compared fibrotic and non-fibrotic ILD. RESULTS: A total of 334 participants were included. The COPM showed moderate test-retest/intra-rater and inter-rater reliability (ICC2,1 = 0.68[0.57-0.77]-0.72[0.63-0.80]), with SEM = 1.08-1.42 and MDC95 = 3.00-3.94, and no floor/ceiling effects. The PFSDQ-M demonstrated excellent internal consistency (α = 0.90-0.96) and good test-retest and inter-rater reliability (ICC2,1 = 0.80[0.74-0.85]-0.92[0.89-0.94]), with SEM = 15.80 and MDC95 = 43.80 for total score. Bland-Altman analysis showed no systematic bias for the COPM and a small bias for the PFSDQ-M test-retest. Moderate-to-strong correlations with LCADL/CIS-8 and weak-to-moderate with 6MWT/1-minSTS supported convergent validity for PFSDQ-M. Negligible-to-weak correlations with age and lung function for COPM and PFSDQ-M supported divergent validity. Subgroup results were similar. CONCLUSION: The European Portuguese COPM and PFSDQ-M demonstrated reliability. The COPM showed evidence of divergent validity, whereas the PFSDQ-M demonstrated both convergent and divergent validity. These findings support their use for assessing functional performance in people with ILD.
Human vaccines & immunotherapeuticsMajdi M Sabahelzain, Maria Christou-Ergos, Julie Leask
Seasonal influenza vaccination reduces the risk of contracting influenza. In Australia, vaccination coverage is consistently low among the most at-risk groups eligible for the free influenza vaccine. To establish an annual national monitoring of the behavioral and social drivers of influenza vaccination, we validated the World Health Organization's Behavioral and Social Drivers of Influenza Vaccination survey. Ours is the first study reporting the validation results of the newly developed survey tool. Two validation stages occurred: first, cognitive interviews and survey item revisions based on feedback; second, collecting quantitative data, performing psychometric analysis, including factor analysis, and assessing the association between survey items and influenza vaccination intention using polychoric correlation and a random forest model to determine each item's importance. We modified nine of the 31 survey items based on cognitive interviews with 16 adults. Based on the psychometric evaluation of 2055 respondents, we identified and validated five factors that underlie the survey structure and aligned well with the four domains of the BeSD framework: Thinking and Feeling, Social Processes, Motivation, and Practical Issues. Each item correlated with the intention to receive influenza vaccine, particularly those related to perceived vaccine importance and social responsibility. We recommend further validation in various contexts, especially to assess the survey's predictive validity regarding actual vaccination uptake.
Human vaccines & immunotherapeuticsRanee Joy B Jacobo, Michael L Villa, Maria Jocelyn C Isidro, Sahra May O Paragas
Adults with diabetes mellitus are at increased risk of vaccine-preventable infections and complications. Despite recommendations for adult immunization, uptake remains suboptimal in many low- and middle-income countries, including the Philippines, where data remain limited. This cross-sectional study assessed adult immunization coverage and associated clinical and sociodemographic factors among Filipino adults with diabetes recruited from inpatient, outpatient, and community outreach settings at a tertiary hospital. Uptake of influenza, pneumococcal, herpes zoster, hepatitis B, tetanus-diphtheria-pertussis (Td/Tdap), and COVID-19 vaccines was evaluated using prespecified operational definitions. Crude associations and parsimonious multivariable logistic regression models were examined; COVID-19 vaccination was not modeled because only six participants were unvaccinated. Among 284 participants (mean age 61.5 ± 12.7 y, 55.6% females), uptake was 44.4% for influenza, 49.6% for pneumococcal, 18.1% for herpes zoster, 15.5% for hepatitis B, 23.2% for Td/Tdap, and 97.9% for the primary COVID-19 series. Males had lower adjusted odds of influenza and pneumococcal vaccination, while increasing age was associated with pneumococcal uptake. Middle and high household income and diabetes duration of 5-10 y were associated with influenza vaccination. Among adults aged ≥50 y, male sex and high income were associated with herpes zoster vaccination. High income was also associated with hepatitis B and Td/Tdap uptake. Provider recommendation was associated with all outcomes, while lack of provider recommendation, failure to prioritize vaccination, and financial constraints were common reasons for non-vaccination. Uptake was uneven and low for most recommended adult vaccines. Integrating vaccine assessment and counseling into diabetes care while addressing financial and access barriers may improve uptake.
PulmonologyWang Chun Kwok, Kelvin Kai Wang To, Frankie Chi Fat Ko, Herbert Pang, Isaac Sze Him Leung, Wai On Tam, Chi Hung Chau, Anthony Shing Yiu Yu, Hon Cheung Fan, Cha…
BACKGROUND: Roflumilast demonstrated anti-inflammatory activity in COPD. While bronchiectasis is also characterised by neutrophilic inflammation, there is a lack of evidence on the use of roflumilast in bronchiectasis. METHODS: An open‑label observation study with an exploratory nature was conducted in Hong Kong. The primary outcome measure was 24-hour sputum volume. The extent of airway inflammation was indicated by sputum leucocyte density, pro-inflammatory cytokines and neutrophil elastase. All eligible patients were treated with roflumilast, starting at 250 µg daily with possible escalation to 500 µg daily if tolerated. RESULTS: A total of 39 patients were started on roflumilast with 24 (61.5%) completed 12 weeks of treatment and 9 of them escalated to 500 µg daily. There were no significant changes in mean daily sputum volume. The median sputum leucocyte density and TNF-α significantly decreased from the recruitment visit to 12 weeks. In extrapolatory analyses, patients with a baseline daily sputum volume ≥ 20 mL might be more likely to respond with a reduction in sputum volume. CONCLUSION: Roflumilast treatment in non-CF bronchiectasis could provide anti-inflammatory effects with a significant reduction in sputum leucocyte density and TNF-α level over 12 weeks of treatment. Extrapolatory analyses suggested potential benefits in sputum volume reduction among the subgroup with baseline daily sputum volume ≥ 20 mL.
Artificial cells, nanomedicine, and biotechnologyHuiqian Yang, Hongjie Du, Chunyan Zang, Jian Liu, Zheng Wang, Fenglei Xu, Hui Li, Xiaoming Li
This study aimed to identify key biomarkers for obstructive sleep apnoea (OSA) by analysing RNA-seq (GSE75097: 6 control and 42 OSA) and single-cell RNA-seq (GSE214865: 11 control and 11 OSA) datasets. Differential expression analysis revealed 575 DEGs between OSA and control groups. Using weighted gene co-expression network analysis (WGCNA) combined with machine learning approaches (Random Forest, SVM-RFE and LASSO), we identified four hub genes (C17ORF91, HBEGF, PGBD2 and ZNF616) as candidate biomarkers, showing exploratory discriminatory performance (AUC > 0.7). Gene set enrichment analysis (GSEA) revealed that these genes are associated with pathways related to hypoxia response, atherosclerosis and metabolic reprogramming (NES as low as -2.049, adj. p < .05), as well as immune regulation (NES up to 1.932, adj. p < .05). Single-cell RNA sequencing analysis further demonstrated that cMonocytes play a central role in OSA progression, exhibiting the highest scores for hypoxia, metabolic dysfunction and atherosclerosis risk. An exploratory nomogram incorporating these hub genes showed favourable internal performance within the discovery cohort. These findings provide hypothesis-generating insights into the molecular features associated with OSA and identify these genes as candidate biomarkers that require independent external and functional validation. Further validation of these genes may provide a basis for evaluating their potential diagnostic and therapeutic relevance in OSA.
Annals of medicineZehua Yang, Wei Li, Yanan Cui, Tingting Huang, Xingyao Tang, Yaodie Peng, Rui Su, Xu Chu, Yong Li, Chunyu Zhang, Cunbo Jia, Ke Huang, Ting Yang
BACKGROUND: Chronic obstructive pulmonary disease (COPD) exhibits significant clinical heterogeneity. This study integrates phenotype identification with longitudinal lung function analysis to develop a prediction tool for rapid decline in a large Chinese cohort. METHODS: This study included 38,863 COPD patients from a national multicenter screening program. Latent class analysis identified clinical phenotypes. Among 1,215 patients with baseline and 24-month follow-up spirometry, rapid decline was defined as annual FEV1 decline ≥40 mL or FEV1% predicted decline >1.5%. LASSO regression and the Boruta algorithm selected predictive variables. Six machine learning models were constructed and evaluated for discrimination, calibration, and utility. SHAP analysis was employed for interpretation. RESULTS: Three distinct phenotypes were identified: Phenotype 1 (GOLD Stage 2, non-smoking females, 25.8%), Phenotype 2 (GOLD Stage 1, smoking males, 44.8%), and Phenotype 3 (GOLD Stage 3, severe smokers, 29.4%). Phenotype 2 exhibited the highest rapid decline rate (55.8%). The CatBoost model achieved optimal performance (AUC 0.712) using six variables: region, fuel type, income level, wheezing, hip circumference, and baseline FEV1. SHAP identified baseline FEV1 as the top predictor. At a threshold of 0.365, the model attained 95.5% sensitivity and 86.4% negative predictive value, with significant net benefit. CONCLUSION: Three clinical phenotypes were identified among COPD patients. Phenotype 2 exhibits the highest risk of rapid progression, representing a key target group for intervention. The predictive model, based on six simple indicators, serves as a valuable tool for screening high-risk rapid decliners.
Clinical and experimental hypertension (New York, N.Y. : 1993)Weijie Tang, Jinzhou Cai, Shibiao Zhang, Yichen Li, Mi Tang, Zilong Zheng, Zhi Tu, Xiuneng Li, Chengzhi Xu, Wangping Chen, Chengming Fan, Jinfu Yang
BACKGROUND: Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease (CHD) with a left-to-right shunt, particularly ventricular septal defect (VSD). In patients presenting with severe PAH, therapeutic decision-making remains challenging because precise and individualized assessment criteria are lacking. In current clinical practice, treatment strategies are often based mainly on isolated hemodynamic parameters obtained by right heart catheterization (RHC), which may not fully reflect disease severity or reversibility. OBJECTIVES: This study aimed to explore an individualized treatment strategy for patients with severe VSD-PAH by analyzing the relationships among peripheral arterial oxygen saturation (SaO2), pulmonary vascular resistance (PVR), pulmonary-to-systemic blood flow ratio (Qp/Qs), and pulmonary-to-systemic pressure ratio (Pp/Pa). METHODS: We retrospectively analyzed 121 patients with isolated VSD and severe PAH admitted to our center between 2010 and 2020. All patients underwent RHC. Correlations between SaO2 and PVR, Qp/Qs, and Pp/Pa were assessed using Spearman correlation analysis. Patients were stratified according to SaO2 levels, and treatment strategies were compared across different hemodynamic profiles using Fisher's exact test. Based on these findings, we established a scoring system integrating SaO2, PVR, Qp/Qs, and Pp/Pa, and categorized total scores to examine their association with actual treatment strategies. RESULTS: The distribution of treatment strategies differed significantly across combinations of SaO2 and PVR, whereas Qp/Qs and Pp/Pa provided limited additional discrimination when SaO2 exceeded 93%. The proposed scoring system was associated with observed treatment patterns: patients with total scores ≥ 60 were predominantly managed surgically (with or without preoperative medical therapy), whereas those with scores <40 were mainly treated with medical therapy alone (93.7%). Intermediate score ranges were associated with mixed treatment patterns. CONCLUSIONS: Combining SaO2 with RHC-derived parameters provides a more comprehensive and individualized assessment of disease severity in VSD-PAH than hemodynamics alone. The proposed multidimensional scoring system may provide a hypothesis-generating framework for cardiovascular specialists.
INTRODUCTION: Early targeted antibiotic therapy is critical for improving outcomes in ICU patients with pneumonia unresponsive to initial treatment. Metagenomic next-generation sequencing (mNGS) is a unique diagnostic tool; however, its effectiveness for high-risk populations remains unclear. METHODS: This retrospective study included 642 ICU patients with pneumonia unresponsive to initial treatment, categorized into single- or repeat-test groups based on mNGS testing frequency. We analyzed the results of mNGS and conventional microbiological tests (CMTs), compared microbial detection characteristics between patients with different immune statuses, assessed the impact of repeat testing on microbial detection and treatment adjustments and evaluated its association with patient prognosis using multivariable logistic regression and propensity score matching. RESULTS: Among 642 patients, patient-level agreement between mNGS and CMTs was low (κ = 0.180, p < 0.001). First bronchoalveolar lavage fluid (BALF)-mNGS results showed a higher microbial detection rate in immunocompromised than immunocompetent patients. Among patients undergoing repeat BALF-mNGS testing, partial concordance between first and second tests was most common pattern. Antibiotic treatments were modified in 67.6% of cases based on mNGS results, with a higher adjustment rate in the repeat-test group. Although ICU mortality was higher in the repeat-test group, multivariate logistic regression analysis revealed no significant association between repeat testing and mortality risk (adjusted odds ratio = 1.15, 95% CI: 0.64-2.06, p = 0.630). After propensity score matching, no significant difference was observed between two groups (absolute risk difference: 1.12%, 95% CI: -7.43% to 9.67%, p = 0.798). CONCLUSION: mNGS is a valuable microbial detection tool for ICU patients with pneumonia unresponsive to initial treatment and can support early antimicrobial adjustment. Repeat testing can provide information on dynamic changes in the microbial spectrum during disease but was not associated with improved patient outcomes, suggesting that repeat testing frequency should be carefully considered to avoid unnecessary testing. mNGS results should be interpreted in conjunction with CMTs, host immune status and inflammatory biomarkers to optimise its clinical value in ICU pneumonia.
International journal of circumpolar healthFariba Kolahdooz, Moutasem Zakkar, Ghazal Kolahdooz, Farzad Akbaryan, Claire Manning, Adrian Wagg, Arja Rautio, Sami Pirkola, Carolyn Gotay, Debbie DeLancey, G…
The COVID-19 pandemic disrupted healthcare access globally through restrictions aimed at limiting virus transmission. Using a cross-sectional design, this project explored perceived barriers to and facilitators of healthcare access during the pandemic in remote Indigenous communities in Northwest Territories (NWT), Canada. Convenience sampling was utilised to recruit self-identifying Indigenous adults (≥18 years) within 10 NWT communities. Information was collected through an interviewer-administered questionnaire exploring experiences with, barriers to, and facilitators of healthcare access during the COVID-19 pandemic. Among the 287 participants (mean age 41.63 years; 66.55% women), 17.42% reported having avoided healthcare service utilisation during COVID-19 due to the risk of exposure. Of participants with a current prescription, 15.73% reported difficulty accessing prescription medications. Some partcipants (7.69%) reported difficulty accessing traditional medicines and healers. The participants reported that many services were disrupted by shortages of healthcare providers, service delays and cancellations, public health measures, and medical travel disruptions. A total of 35.89% of participants utilised virtual care, and while many found it was convenient for certain needs, some reported that it was inadequate. The findings highlight the perceived challenges to healthcare access in NWT during the pandemic. These challenges are closely tied to the healthcare context in the region, which depends heavily on medical travel and visiting specialist clinics.
Human vaccines & immunotherapeuticsSarang K Yoon, Andrew L Phillips, Hongwei Zhao, Feiyun Yan, Danli Chen, Yan Zhuang, Matthew S Thiese, Elizabeth A K Rowley, Jacob McKell, Adam Yates, Joshua Gr…
The objective of this analysis was to assess reactogenicity profile differences between a protein- and mRNA-based COVID-19 vaccine in participants who had previously received ≥2 doses of an mRNA-based vaccine in a real-world, double-blinded, randomized, controlled trial. In the BEEHIVE/NCT06065176 trial (ClinicalTrials.gov: NCT06065176), participants randomized 1:1 received one dose of the Novavax (NVX) or Pfizer-BioNTech (PFZ) COVID-19 vaccine 2023-2024 formulation (XBB.1.5); a comparator group did not receive a dose. Electronic surveys collected solicited systemic (fatigue, fever, headache, joint pain, malaise/feeling sick, muscle pain, and nausea/vomiting) and local (injection-site pain, tenderness, and swelling) events on days 1, 2, and 6 after study vaccination. Significantly lower proportions of participants in the NVX (n = 448) vs. PFZ (n = 453) group reported a systemic (62.1% vs. 75.7%; risk difference -13.7%, 95% CI: -19.6% to -7.7%) or local (81.0% vs. 92.7%; risk difference -11.7%, 95% CI: -16.0% to -7.3%) event in the day-1 survey (both Cochran-Mantel-Haenszel P < .0001). Most events were mild. Reactogenicity rates decreased throughout the week; >80% and >94% of participants in either group reported no systemic or local reactogenicity, respectively, in the day-6 survey. Mean number of events/person were significantly lower for the NVX vs. PFZ group in the day-1 (systemic and local) and day-2 (local) surveys (each P < .0001). There were significant differences in reactogenicity profiles for the 2023-2024 formulations of the NVX and PFZ COVID-19 vaccines, with NVX consistently associated with lower reactogenicity rates than PFZ.
The Libyan journal of medicineMadjda Akacha, Abdelhalim Khenchouche, Mounira Amrane, Abbas Mehnane, Abdelmadjid Lacheheb, Nasir A Ibrahim, Nosiba S Basher, Mohammed Saad Aleissa, Assia Derg…
The COVID-19 pandemic revealed the importance of pre-existing conditions, or comorbidities, as major predictors of disease severity and mortality worldwide. In this context, the major goal of this study was to examine the impact of common comorbidities on the clinical outcomes of COVID-19 patients in Sétif, Algeria, as well as to evaluate the local epidemiological risk profile. We conducted a thorough analysis of 12,932 COVID-19 participants in the Sétif community, focusing on the prevalence and impact of many illnesses, most notably diabetes, cardiovascular disease (CVD), and hypertension. We also looked at geographical inequalities in comorbidity prevalence to help influence local patient care methods. Our data revealed a strong link between these comorbidities and poor COVID-19 outcomes. Patients with heart disease, hypertension, and diabetes had a considerably greater incidence of severe COVID-19, with computed odds ratios (ORs) of 1.50, 1.34, and 2.89, respectively, indicating that diabetes was the best predictor of severity in this cohort. This investigation demonstrated that the presence of comorbidities considerably exacerbated the severity and mortality rate of SARS-CoV-2 infection. These findings highlight the importance of establishing thorough, personalised techniques and more effective diagnostic and treatment approaches for COVID-19 patients that explicitly account for the varied prevalence of underlying health issues.
PulmonologyRaffaella Manzo, Giuseppe Fiorentino, Anna Michela Gaeta, Antonietta Coppola, Valentina Di Spirito, Maurizia Lanza, Angela Mirizzi, Ilaria Ferrarotti, Nuccia G…
BACKGROUND: :Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder mainly affecting the lungs and liver, but its psychological, functional, and relational burden remains insufficiently characterizedcharacterised. OBJECTIVE: To describe emotional distress, health-related quality of life, interpersonal and sexual difficulties, and daily functional limitations in individuals with AATD. METHODS: We conducted a cross-sectional online survey in Italy between October and December 2025 among individuals with AATD. Socio-demographic, clinical, and psychosocial data were collected using an ad hoc questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the 12-item Short Form Health Survey (SF-12). HADS subscales were reconstructed from item-level responses, applying reverse scoring where appropriate. RESULTS: The study included 130 participants (mean age 56.3 ± 13.5 years; 53.8% female). Pulmonary involvement was the most frequent manifestation (68.5%). Disease-related limitations were reported in daily functioning by 57.7% and in social participation by 53.1%. Clinically significant symptoms were present in 46.2% for anxiety and 17.7% for depression. The SF-12-derived ad hoc unweighted physical and mental descriptive composites were 56.68 ± 27.47 and 54.53 ± 26.91. Women reported higher anxiety and poorer mental-composite scores, while participants receiving augmentation therapy showed worse depressive and perceived-health burden. Sexual-life changes were reported by 37/96 partnered participants (38.5%). Fifteen of 128 respondents (11.7%; two preferred not to answer) reported current psychological support. In exploratory covariate-adjusted models, functional and perceived-health correlates remained associated with clinically significant anxiety. CONCLUSIONS: In this cross-sectional survey, respondents with AATD reported substantial emotional, functional, and relational burden, while few were receiving psychological support. The self-selected sample and absence of a non-AATD comparison group preclude causal or disease-specific inference; the findings support evaluation of brief psychological screening and defined referral pathways in multidisciplinary AATD care.
Global public healthChiamaka Henrietta Onyebuchi, Jiyong Jin
The inequities observed during the COVID-19 pandemic were not an accident. They reflect deeper patterns of injustice already embedded in rules, financing models and power arrangements in global health governance. This paper argues that the paradigm of ethical health sovereignty offers a moral countermodel to the dependency shaping global health relations. It examines how sovereignty, solidarity and justice are being reinterpreted after the pandemic by drawing on the WHO Pandemic Agreement (A78/10, 2025) and Africa's regional responses through the African Union and Africa Centres for Disease Control and Prevention. The Agreement represents a partial moral advance by acknowledging equity and shared responsibility while still leaving hierarchy intact through voluntarism and sovereignty-based limits. In contrast, Africa's pooled procurement, regulatory harmonisation and coordinated diplomacy show solidarity as shared governance rather than charity. The paper concludes that global health equity requires redesigning governance so that fairness is built into institutions and sovereignty is understood as shared and cooperative decision-making.
OncoimmunologyMehmet Haluk Yucel, Maral Martin Mildanoglu, Ebru Engin Delipoyraz, Hakan Ozcelik, Erdem Sunger, Sena Fidan, Cihat Terzioglu, Tansel Cakir, Harun Muglu, Burcin…
Growing evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors across multiple malignancies. However, evidence in extensive-stage small cell lung cancer (ES-SCLC) remains limited to a single East Asian cohort, and independent validation in other populations is lacking. We conducted a retrospective single-center cohort study of 107 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab. The time of day of administration (ToDA) was defined as the median start time of the first four immunotherapy infusions, and patients were categorized according to the cohort median ToDA. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The cohort median ToDA was 11:54. Patients treated before the median ToDA had significantly longer median PFS (9.07 vs. 7.23 months, p = 0.002) and OS (21.17 vs. 11.43 months, p = 0.002) than those treated later. In multivariable Cox regression analysis, later administration remained independently associated with shorter PFS (adjusted HR 1.63, 95% CI 1.03-2.58; p = 0.038) and OS (adjusted HR 1.65, 95% CI 1.00-2.71; p = 0.049), whereas objective response rates, treatment-related toxicity, and immune-related adverse events were comparable between groups. Morning administration of first-line chemoimmunotherapy was associated with significantly longer survival without increased toxicity in patients with ES-SCLC. These findings support growing evidence that circadian timing may influence immune checkpoint inhibitor efficacy and warrant prospective evaluation of treatment timing as a readily modifiable strategy to optimize immunotherapy delivery.
Human vaccines & immunotherapeuticsDaniela Amicizia, Federico Grammatico, Elvira Massaro, Irene Schenone, Francesca Marchini, Matteo Astengo, Andrea Fiorano, Andrea Orsi, Giancarlo Icardi, Filip…
The aim of the present study is to evaluate the 2023/24 and 2024/25 influenza vaccination campaigns in Liguria (Italy), specifically analyzing how the transition toward a proximity-based model impacted vaccine appropriateness across different age groups (60-64 y, ≥65 y) and providers. Data regarding seasonal influenza vaccine administrations were extracted from the official Local Health Units (LHUs) immunization registries, which aggregate immunization records from different providers [LHUs, General Practitioners (GPs), pediatricians and community pharmacies]. To evaluate prescriptive appropriklateness, administered vaccines were cross-referenced with national guidelines based on the patient's age. A 6% overall decrease in coverage rates between the two seasons was recorded while the provider landscape shifted significantly. Unfortunately, while enhancing proximity (General Practitioners and pharmacies), this evolution introduced wide variability in prescriptive appropriateness. Our analysis reveals a persistent mismatch between national recommendations and real-world clinical practice and only 65% (2023/24 season) and 73% (2024/25 season) among ≥65 y individuals received enhanced vaccines. Strengthening clinical governance and targeted professional training for pharmacists and GPs is essential to ensure that the convenience of proximity-based vaccination does not compromise clinical efficacy through the use of sub-optimal vaccine platforms for high-risk cohorts.
Annals of medicineYequan Xu, Ying Zhang, Danni Ye, Shanyu Jiang, Renqiang Yu
BACKGROUND: Despite advances in perinatal care and improved survival of preterm infants, bronchopulmonary dysplasia (BPD) remains a major neonatal morbidity with long-term consequences. Accurate early risk prediction is therefore clinically important. Conventional models may be limited in capturing the complex and nonlinear interactions underlying BPD, whereas machine learning offers greater flexibility for high-dimensional clinical data. However, limited interpretability remains a barrier to clinical implementation. METHOD: This retrospective study included 1,083 preterm infants with gestational age <32 weeks and birth weight <2,500 g admitted to the Affiliated Women's Hospital of Jiangnan University from January 2011 to December 2025. Data were split 7:3 into training and validation sets. Seven models were evaluated, with hyperparameters optimized by 10-fold cross-validation using AUC. Missing data were handled by complete case analysis. Performance was assessed using AUC-ROC, Brier score, and decision curve analysis (DCA), while SHAP and partial dependence plots (PDP) were used for interpretation. The optimal model was externally validated in an independent cohort of 1,000 neonates. RESULT: GBM showed the best internal performance, with an AUC of 0.880, accuracy of 0.793, sensitivity of 0.827, specificity of 0.759, and Brier score of 0.141. Birth weight, gestational age, and 1-minute Apgar score were the leading predictors. Neonatal anemia was strongly associated with BPD (aOR = 5.036, 95% CI: 3.35-7.57). PDP demonstrated a nonlinear association between birth weight and BPD risk, with a sharp increase between 1,250 and 1,500 g. DCA indicated favorable net clinical benefit across relevant threshold probabilities. CONCLUSION: The GBM model provides interpretable, individualized early BPD risk estimates using routinely available clinical variables and may support identification of high-risk preterm infants. It is intended for risk stratification rather than treatment guidance. Prospective multicenter validation is required before routine clinical implementation.
Global health actionDalia Hyzam, Taha Al-Mahbashi, Fekri Dureab, Timo Ulrichs
BACKGROUND: Health system resilience is often described through the World Health Organization building blocks, yet in protracted crises it depends on whether governance, financing, workforce, information systems, service delivery, and accountability can convert crisis response into institutional reform. OBJECTIVE(S): This study examines how far Yemen's health system responses to prolonged conflict, economic decline, disease outbreaks, and COVID-19 progressed beyond absorptive and adaptive resilience toward transformative resilience, and how strategic health policy across the building blocks shaped this transition. METHODS: We conducted 30 in-depth interviews with national and subnational policymakers and health leaders in Yemen between May and July 2025. Data were analysed in ATLAS.ti 25 using framework-informed thematic analysis that combined a priori categories from the World Health Organization health system building blocks and resilience capacities with inductively developed empirical codes. RESULTS: Yemen demonstrated externally buffered absorptive capacity sufficient to prevent complete system collapse, together with uneven and localised adaptation through crisis committees, donor-supported financing, temporary workforce mobilisation, intensified surveillance, oxygen and isolation capacity, and referral workarounds. However, these responses were largely reactive, donor-dependent, and unevenly institutionalised. Transformative resilience remained constrained by fragmented authority, under-protected recurrent financing, workforce instability, weak data-to-decision pathways, limited referral governance, and the absence of formal learning-to-reform mechanisms. CONCLUSIONS: Yemen's experience shows that resilience in protracted crisis settings should be judged not only by the survival of repeated shocks, but by whether absorptive and adaptive gains are converted into institutional capability through strategic policy alignment across the health system.
PulmonologyXiu Shi, Jinyan Ke, Xiaofeng Wu, Yuhan Wang, Yixuan Wang
BACKGROUND: Whether supranormal lung function is associated with incident atrial fibrillation (AF), and whether obstructive sleep apnoea (OSA) modifies this association, remain to be determined. METHODS: We analysed 2,408 participants from the Sleep Heart Health Study who were free of AF at baseline and had no spirometric airflow obstruction. The primary analysis classified forced expiratory volume in 1 second (FEV1) as below normal, normal, or supranormal using race-neutral Global Lung Function Initiative (GLI) Global (2022) reference equations. Categories defined by forced vital capacity (FVC) were examined in a secondary analysis. Associations with incident AF were evaluated using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Firth penalised logistic regression and sensitivity analyses were used to assess the robustness of the findings. Interaction with OSA was explored. RESULTS: Among 2,408 participants, 282 developed AF. Compared with normal FEV1, supranormal FEV1 was associated with lower odds of incident AF in the primary adjusted model (OR, 0.420; 95% CI, 0.198-0.888). The corresponding Firth estimate was 0.443 (95% CI, 0.199-0.869). Supranormal FVC showed a similar association in standard logistic regression (OR, 0.351; 95% CI, 0.167-0.736) and Firth penalised logistic regression (OR, 0.371; 95% CI, 0.168-0.721). The direction of the associations was generally consistent across sensitivity analyses. There was no statistically significant evidence of effect modification by OSA. CONCLUSIONS: Supranormal lung function was associated with lower odds of incident AF. These findings support supranormal spirometry as a potential marker of favourable systemic and cardiopulmonary physiology.
Background: Surfactant-related gene (SRG) variants are an emerging cause of interstitial lung disease/pulmonary fibrosis (ILD/PF). Accurate recognition of these disorders is relevant for diagnosis, genetic counselling, and clinical management.Reaserch question: How do SRG-associated ILD/PF present in adults, and what clinical, radiological, and histopathological features characterize their phenotype?Study design and methods: We performed a systematic review (PROSPERO CRD42024517610) to describe the clinical features, management, and outcomes of adults with SRG-related ILD/PF. PubMed, Embase, and Web of Science were searched from January 2000 to December 2024 for studies reporting adults (≥18 years) with genetically confirmed SRG variants and ILD/PF. Demographic, clinical, radiological, histological, functional, treatment, and lung transplantation (LT) data were extracted.Results: Thirty-eight studies included 162 adults carrying class 3-5 variants in SFTPA1/2 (61), SFTPC (52), ABCA3 (31), NKX2-1 (16), and SFTPB (2), including 35 novel variants. Age at diagnosis ranged from 19 to 79 years. Familial ILD predominated in SFTPA1/2, frequently associated with personal or familial lung cancer, whereas NKX2-1 variants showed thyroid and neurological involvement. Lung function typically demonstrated mild-to-moderate restriction with impaired diffusing capacity. Chest CT findings were heterogeneous and often indeterminate, while usual interstitial pneumonia was the predominant histological pattern except in ABCA3-related disease. Treatment approaches varied considerably; LT provided favourable outcomes in selected patients.Conclusion: Adult SRG-related ILD/PF is likely under-recognised because of variable penetrance, wide age at onset, and non-specific imaging features. International registries are needed to improve genotype-phenotype correlations and guide personalised management.
Sleep medicineHephzibah O Ali, Michelle Gyenes, Henry T H Xie, Maneesha Kamra, David R Colelli, Nardin Kirolos, David J Gladstone, Karl Boyle, Arun N E Sundaram, Julia J Hop…
Obstructive sleep apnea (OSA) is highly prevalent among patients with stroke and transient ischemic attack (TIA) and is associated with poor outcomes including post-stroke depression. Continuous positive airway pressure (CPAP) is the standard treatment for OSA, however, adherence is low. The relationship between CPAP adherence with post-stroke depression and other outcomes has not been well-defined. This study aimed to evaluate whether CPAP adherence was associated with changes in depressive symptoms and other post-stroke/TIA outcomes. This was a secondary analysis of a prospectively collected cohort study of 112 patients with imaging-confirmed stroke or physician-diagnosed TIA who were diagnosed with OSA via in-laboratory polysomnography or home sleep apnea testing. Of 112 patients, 36 (32.1%) were adherent to CPAP and 76 (67.9%) were non-adherent. When CPAP adherence was modeled continuously, greater weekly CPAP use was associated with reduced depressive symptoms (β = -0.07 per hour/week; 95% CI -0.14 to -0.003; p = 0.04) while controlling for our covariates of interest. Model-based predictions indicated that the estimated change in depressive symptoms became statistically different from no change at approximately 31 h of CPAP use per week. Stroke recurrence occurred only in the non-adherent group (adherent: 0/36, 0%; non-adherent: 3/76, 3.9%). A dose-dependent relationship was observed between greater CPAP use and improvement in depressive symptoms, suggesting benefits beyond a conventional CPAP adherence threshold. These findings highlight the importance of encouraging CPAP use in post-stroke/TIA populations as it may confer clinically meaningful mood benefits.
Expert review of vaccinesDan'er Lin, Xiangting Zhang, Junxian Hu, Xiaohua Li, Lin Yao, Jianyun Lu, Zhiyun Wang, Yanfang Chen, Yihan Lu
BACKGROUND: Healthcare workers (HCWs) play a key role in recommending influenza vaccination. Few studies have examined HCWs' influenza vaccination and recommendation behavior in China. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted among HCWs in primary health centers, secondary and tertiary hospitals, and schools in Guangzhou, China, in January 2026. RESULTS: Among 3,153 HCWs, 46.2% reported vaccination in at least one of latest four influenza seasons. Average seasonal uptake was 28.2%. Uptake varied by occupation, with higher uptake among public health practitioners (OR = 2.53, p < 0.001) and lower among school healthcare providers (OR = 0.64, p < 0.001), compared with physicians. Knowledge of influenza was negatively associated with vaccination (OR = 0.90, p < 0.001), whereas knowledge of influenza vaccines was positively associated with vaccination (OR = 1.09, p < 0.001) and recommendation behavior (OR = 1.11, p < 0.001). Personal vaccination was positively associated with recommendation behavior (OR = 3.12, p < 0.001). Exploratory generalized path analysis showed knowledge of influenza vaccines was positively associated with recommendation behavior (β = 0.131), mainly through recommendation attitude and personal vaccination, whereas opposite indirect pathways for knowledge of influenza resulted in no significant association. CONCLUSIONS: Influenza vaccine uptake remained insufficient among HCWs. Different knowledge domains showed diverse association with vaccination and recommendation behavior. Vaccine-specific knowledge and risk-benefit perceptions were more consistently associated with HCWs' vaccination and recommendation practices.
Sleep medicineDiana Carolina De la Hoz Díaz-Granados, Hernando Gaitán Duarte, Elida Dueñas-Meza, Nadia Juliana Proaños-Jurado, Luis F Giraldo-Cadavid
OBJECTIVE: To examine whether obstructive sleep apnea (OSA) is associated with pro-B-type natriuretic peptide and its N-terminal fragment (proBNP/NT-proBNP), a blood marker of myocardial wall stress, and with echocardiographic measures of cardiac size and function in children living at high altitude. METHODS: 274 children aged 5-16 years living in Bogotá, Colombia (2660 m) underwent overnight polysomnography, from which OSA and hypoxic-burden measures (oxygen desaturation index, percentage of sleep time with oxygen saturation below 90%) were derived. Serum proBNP/NT-proBNP and interleukin-10 (IL-10, an anti-inflammatory cytokine) were measured by enzyme-linked immunosorbent assay, and pediatric cardiologists performed echocardiography. STATISTICAL ANALYSIS: proBNP/NT-proBNP was analysed with median regression adjusted for sex and body mass index z-score; six echocardiographic outcomes were tested with Holm correction; hypoxic-burden and IL-10 analyses were exploratory. RESULTS: 187 (68%) children had OSA. Median proBNP/NT-proBNP was higher with OSA (adjusted ratio of medians 1.56, 95% confidence interval 1.02-2.39). No echocardiographic outcome differed after correction (all Holm-adjusted p ≥ 0.14). In exploratory analyses, a higher oxygen desaturation index was associated with higher proBNP/NT-proBNP (p = 0.014), but this did not remain after false-discovery-rate correction (q = 0.22). IL-10 analyses were exploratory. CONCLUSIONS: In children living at 2660 m, OSA was associated with higher proBNP/NT-proBNP but not with echocardiographic differences. Longitudinal, multi-altitude studies are needed.
Global public healthSarah Marion Nakachwa, Pascal Mathew Okorobe, John Onama
Uganda hosts one of Africa's largest refugee populations, yet displaced and migrant communities face persistent barriers to routine immunisation. Despite commitments to vaccine equity, many remain unprotected against preventable diseases. This narrative review synthesises evidence from peer-reviewed studies, national surveys, and institutional reports up to September 2025 to assess immunisation coverage, challenges, and potential solutions among refugees and migrants in Uganda. The findings indicate that vaccination rates in refugee communities are generally lower than national averages due to administrative barriers, vaccine shortages, long distances to health facilities, language difficulties, misinformation, and challenges intensified during the COVID-19 pandemic. Economic hardship further limits healthcare access. However, several strategies show promise: integrating refugees into national immunisation systems, simplifying registration processes, strengthening mobile outreach, engaging community health workers, and improving cross-border data coordination. Addressing these inequities requires both technical and social commitment through adequate financing, inclusive policies, and meaningful community engagement. Achieving equitable immunisation for refugees in Uganda is essential for public health protection and the realisation of universal health coverage.
Life science allianceLaura de-la-Puente-Ovejero, Ana Domostegui, Inés María García-Pérez, Gonzalo Aizpurua, Lucía Lomba-Riego, Pilar Ximenez-Embún, Cristina Mayor-Ruiz, Mariano Bar…
Scaffold integrity is essential for the activity of proteins that function through protein-protein interactions rather than catalytic output. RAF1 exemplifies this duality: although it is a bona fide kinase and a core component of the MAPK cascade, its tumor-promoting role is largely kinase-independent, relying instead on scaffold-mediated suppression of apoptosis. Genetic Raf1 ablation in KRAS-driven lung adenocarcinoma mouse models induces tumor regression without systemic toxicity, making it an attractive candidate for targeted protein degradation. Chemogenetic systems like the dTAG platform are widely used for preclinical target validation. Here, we generated a dTAG-RAF1 mouse model and showed that pharmacological degradation is efficient and systemically well tolerated but fails to reproduce the tumor regression observed upon genetic Raf1 ablation. Mechanistically, the N-terminal FKBP12F36V tag (dTAG) perturbs the RAF1 interactome, including scaffold associations with apoptotic regulators, thereby blunting the phenotypic consequences of its degradation. These results establish scaffold integrity as a determinant of chemogenetic system fidelity and argue that degradation tools must be validated at the functional level, not only for target elimination, before assessing their therapeutic relevance.
Hypertension in pregnancyA Medel-Martinez, A Cebollada-Solanas, M Strunk, M Fabre, V M Fernández-Soria, R Ramos-Ruiz, C Paules, D Oros, J Schoorlemmer
INTRODUCTION: SARS-CoV-2 infection during pregnancy has been associated with higher rates of preeclampsia (PE). While placental abnormalities resembling PE have been reported in COVID-19 pregnancies, the molecular mechanisms underlying the association remain unclear. METHODS: We conducted bulk RNA sequencing on placental tissues from four pregnancy groups: uneventful prepandemic (preCOVID-19), prepandemic PE (preCOVID-19 PE), COVID-19 without PE (COVID no PE), and COVID-19 complicated by PE or other hypertensive disorders (COVID PE). Differential expression was analyzed using Deseq2 likelihood ratio test (LRT), and gene set enrichment analysis identified dysregulated pathways. RESULTS: Clustering of LRT-significant differentially expressed genes (DEGs) identified a set of 16 genes (defined by the false discovery rate adjusted p-value < 0.05) across the four pregnancy groups, showing stepwise expression changes-lowest in preCOVID-19 uneventful, followed by those in COVID-19 without PE, then preCOVID-19 PE, and highest in COVID PE. This cluster included genes associated with placental dysfunction, such as LAMA5 and BTNL9. While morphogenesis-related pathways were enriched across all pathological groups, immune activation pathways were predominantly enriched in COVID PE, moderately in preCOVID-19 PE, and absent in COVID no PE. DISCUSSION: Our findings identify a COVID-19-associated placental signature that mirrors PE features and shows a progressive expression pattern defining a continuum of placental stress, with maternal SARS-CoV-2 infection potentially exacerbating underlying dysfunction.
Emerging microbes & infectionsMasato Hatta, Ying Huang, Jeremy A Duke, Joseph R Rouse, Chenchen Feng, Xudong Lin, Li Wang, Melvyn R Almanzar-Jordan, Zhu-Nan Li, James Stevens, Min Z Levine,…
Limited A(H5)-specific vaccine supply is expected early in a potential A(H5N1) pandemic, raising the question of whether licensed seasonal influenza vaccines could enhance protection when administered before A(H5) vaccination. We evaluated this strategy in mouse and ferret models using clade 2.3.4.4b A(H5N1) viruses. Seasonal influenza vaccination induced antibodies to seasonal haemagglutinins but did not induce detectable antibodies against A(H5) and did not consistently enhance A(H5)-directed antibody responses after A(H5) vaccination. In lethal challenge studies, seasonal vaccine priming before A(H5) vaccination was associated with improved outcomes compared with A(H5) vaccination alone in one of three mouse experiments, but this effect was not observed in the other two mouse experiments or in ferrets. These findings suggest that seasonal influenza vaccine priming provides limited added benefit to A(H5) vaccine-mediated protection against A(H5N1) under the conditions tested.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupRémi Grange, Antonin Chemin, Nicolas Magand, Noémie Lutz, Elisabeth Daguenet, Sylvain Grange
BACKGROUND: The morphological evolution of lung ablation zones following cryoablation (CA) remains incompletely characterized. This study aimed to describe CT pattern evolution up to 18 months and evaluate the 1-month pattern as an early marker of long-term morphological trajectory. METHODS: This retrospective single-center study included 58 lesions in 28 patients treated with CT-guided CA (triple-freeze protocol, 2020-2024). Non-contrast CT was performed at 1, 3, 6, 12, and 18 months. Ablation zones were classified into five patterns: cavity, nodular, fibrosis, atelectasis, and reversed halo sign (RHS). Univariate analyses explored factors associated with each pattern at 1 and 6 months. RESULTS: At 1 month, cavity predominated (47%), followed by nodular (31%), fibrosis (10%), atelectasis (7%), and RHS (5%). By 6 months, fibrosis became the predominant pattern (43%); by 18 months (n = 34), it reached 65% and cavity disappeared. Median major axis decreased from 29 [22-34] mm to 17 [0-23] mm at 6 months (p < 0.001). Atelectasis at 1 month were associated with persistent atelectasis at 6 months (100%, 7/7 vs. 12/51, 24%; p < 0.001) and pleural contact (p = 0.016). The nodular pattern showed a non-significant trend toward fibrotic resolution (61% vs. 35%, p = 0.087). No procedural variable was associated with CT pattern. CONCLUSION: The 1-month CT pattern may serve as an imaging marker of long-term ablation zone evolution. Atelectasis and RHS were associated with atelectasis, whereas fibrosis became the predominant pattern and cavity disappeared over time. These exploratory findings require prospective validation in larger cohorts.
Sleep medicineKendal Chatard, Joshua Landvatter, Adam Bress, Jenna Duffecy, Molly B Conroy, Sara Simonsen, Chelsea Allen, Tom Greene, Christopher D Sparks, Kelly Baron
OBJECTIVES: Obstructive sleep apnea (OSA) and short sleep duration each contribute to hypertension risk, yet their combined influence on 24-h blood pressure patterns remains poorly characterized. This study evaluated associations between sleep apnea severity (apnea-hypopnea index, AHI), objective sleep duration, and ambulatory blood pressure (ABP). METHODS: This cross-sectional secondary analysis used data from a behavioral sleep extension trial which included adults with self-reported sleep duration <7 h and elevated in-office blood pressure. Wrist-worn actigraphy measured objective sleep duration, a single-night home sleep apnea test assessed OSA severity, and participants completed 24-h ABP monitoring. Linear regression evaluated associations between AHI and mean systolic/diastolic blood pressure (DBP); logistic models examined AHI associations with systolic/diastolic non-dipping. RESULTS: Of 195 participants with valid data, each 10-event/hour higher AHI was associated with higher mean DBP in both the unadjusted model (0.96 mmHg [95% CI 0.20, 1.71]; p = 0.013) and the adjusted model (0.92 mmHg [95% CI 0.10, 1.73]; p = 0.027). For systolic non-dipping, the unadjusted model showed higher odds with higher AHI (OR per 10-event/hour higher AHI 1.34; 95% CI 1.00 to 1.82; p = 0.049). After adjustment for age, sex, race, and BMI, the estimate was similar in direction but did not meet statistical significance (OR 1.35; 95% CI 0.97 to 1.97; p = 0.090). The AHI × sleep duration interaction for systolic non-dipping had p = 0.045. CONCLUSIONS: Among adults with elevated in-office blood pressure and short sleep duration, greater OSA severity predicted higher mean DBP.