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Serum amyloid A as a prognostic biomarker for 30-day mortality in patients with community-acquired pneumonia patients in the emergency department.3 weeks agoCommunity-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality, particularly in older adults. Accurate risk assessment of patients with CAP in the emergency department (ED) is essential for guiding clinical decision-making. This study evaluated the prognostic value of serum amyloid A (SAA) levels for predicting 30-day mortality in patients with CAP presenting to the ED. The data of 398 adult patients with CAP who were admitted to the ED between November 2022 and March 2025 were retrospectively analyzed. Clinical parameters, laboratory biomarkers, and Pneumonia Severity Index (PSI) score were assessed. The primary endpoint was all-cause mortality within 30 days. The overall 30-day mortality rate was 15.8%. SAA levels at ED admission were markedly increased in nonsurvivors compared with those in survivors and demonstrated positive correlations with PSI score and other biomarkers. The area under the curve (AUC) value for SAA levels in predicting mortality was 0.768, which was higher than those for procalcitonin (AUC = 0.671) and high-sensitivity C-reactive protein (AUC = 0.657). The optimal cutoff value for SAA levels was determined to be 280.2 mg/L, yielding a sensitivity of 79.4% and a specificity of 68.5%. Multivariate analysis identified SAA level > 280.2 mg/L, PSI score > 125, intensive care unit admission, and presepsin level > 373 pg/mL as independent predictors of mortality. Thus, increased SAA levels at the time of ED presentation are independently associated with mortality in patients with CAP and may serve as a valuable prognostic biomarker to inform clinical decision-making.Chronic respiratory diseaseAccessCare/ManagementAdvocacyEducation
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Genotype-dependent cell tropism of EV-A71 at the human blood cerebrospinal fluid and blood brain barrier.3 weeks agoEnterovirus A 71 (EV-A71) has caused major epidemics worldwide. While it is most commonly associated with Hand-Foot-Mouth Disease (HFMD) or nonspecific presentations as upper or lower respiratory tract infection, it can also lead to severe neurologic manifestations especially in young children. Detailed understanding of the pathogenesis of EV-A71 CNS invasion as well as of the neurotropic subgenotypes is currently lacking.
EV-A71 infection at the level of the brain barriers was assessed with human in vitro models of the Blood-Cerebrospinal Fluid Barrier (BCSFB) using Human choroid plexus papilloma (HIBCPP) cells and the Blood-Brain Barrier (BBB) using Human brain microvascular endothelial cells (HBMEC). Six clinically relevant genotypes, namely BrCr, B5, C1, C1-like, C2 and C4 were compared. Besides BrCr, the reference strain for EV-A71 and C2, which is known for its worldwide presence, C1 and C1-like were chosen as they are mainly circulating in Europe whereas C4 and B5 are mainly known from the Asian-Pacific region. Infection was analyzed qualitatively via cytopathic effect (CPE) with light microscopy and immunofluorescence staining. Quantification of viral genome copies was performed via qPCR. In parallel, barrier integrity of the BCSFB was monitored via measurement of transepithelial resistance. LIVE/DEAD assays were applied for viability controls.
HIBCPP cells and HBMEC differed in their susceptibility to infection with different genotypes of EV-A71 namely BrCr, B5, C1, C1-like, C2 and C4. None of the strains caused a lytic infection in either model, in contrast to infection in RD cells. In HIBCPP cells as a model for the BCSFB, B5 led to the highest infection rates. Significant differences in the polar release of viral progeny to the CSF side were detected for B5 (56.42 ± 7.13 %) compared to BrCR (30.39 ± 8.11 %), C1 (8.73 ± 8.89 %), C1-like (23.90 ± 17.28 %), C2 (16.89 ± 8.95 %) and C4 (21.46 ± 3.16 %). In HBMEC as a model for the BBB, BrCr showed significantly higher apical release compared to the other genotypes. The minimum p-value (0.0019) was recorded for pBrCrvs.B5 at 24 h and 48 h, while the maximum p-value (0.0379) was observed for pBrCrvs.B5 at 72 h.
Our findings reveal that different genotypes of EV-A71 exhibit distinct tropisms at the level of the brain barriers, which may correlate with variations in the clinical course of infection. Clinical and molecular surveillance of EV infections beyond those currently established in the Asia-Pacific region is warranted.Chronic respiratory diseaseAccessCare/Management -
Respiratory Syncytial Virus (RSV) in an Italian Pediatric Cohort: Genomic Analysis and Circulation Pattern in the Season 2022-2023.3 weeks agoThere is growing interest in the molecular surveillance of the respiratory syncytial virus (RSV) and data concerning the virus molecular epidemiology in high-risk pediatric patients in Italy are still limited. A total of 127 RSV-positive swabs collected in 2022-2023 season were analyzed. Whole genomes were obtained by next-generation sequencing and used for phylogenetic and phylodynamic analyses. A large proportion of the subjects had required hospitalization (78%) and age of hospitalized subjects was significantly lower than that of nonhospitalized (69 vs. 129 days; p < 0.0001). Genomic analysis suggested a significant increase in nucleotide variability in recent samples compared to previous waves and especially in subtype A. Phylogenetic analysis identified 14 and 16 clades including Italian strains in RSV-A and B, respectively. Italian strains tended to group together forming monophyletic groups, 9 in RSV-A and 13 in RSV-B, probably representing local chains of transmission. A few of those pure Italian subclades began in 21-22 wave and persisted for more than 1 year. For both subtypes the skyline plot showed two peaks in transmissions, the first between 2017 and 2019, followed by a temporary reduction in 2021 coinciding with the widespread use of control measures against COVID-19 and the second at the beginning of 2023. Accordingly, the Re estimates showed fluctuating values. This study suggests that the large circulation of RSV following pandemic restrictions is partly due to the introduction of viral strains already circulating across Europe, and partly to strains that persist in our region from one season to the next.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.3 weeks agoIn 2023, an estimated 1.3 million children (aged 0-14 years) became ill with tuberculosis, and 166,000 children (aged 0-15 years) died from the disease. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that detects Mycobacterium tuberculosis complex and rifampicin resistance. This is an update of a Cochrane review first published in 2020 and last updated in 2022. Parts of the current update informed the 2024 WHO updated guidance for the diagnosis of tuberculosis.
To assess the diagnostic accuracy of Xpert Ultra for detecting pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance in children (aged 0-9 years) with presumed tuberculosis.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 6 October 2023.
For study design, we included cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children aged birth to nine years. Regarding specimen type, we included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis); cerebrospinal fluid (tuberculous meningitis); and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). Reference standards for detection of tuberculosis were microbiological reference standard (MRS; including culture) or composite reference standard (CRS); for stool, we considered Xpert Ultra in sputum or gastric aspirates in addition to culture. Reference standards for detection of rifampicin resistance in sputum were phenotypic drug susceptibility testing or targeted or whole genome sequencing.
Two review authors independently extracted data and assessed methodological quality using the tailored QUADAS-2 tool, judging risk of bias separately for each target condition and sample type. We conducted separate meta-analyses for detection of pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance. We used a bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We assessed certainty of evidence using the GRADE approach.
This update included 23 studies (including 9 new studies since the previous review) that evaluated detection of pulmonary tuberculosis (21 studies, 9223 children), tuberculous meningitis (3 studies, 215 children), lymph node tuberculosis (2 studies, 58 children), and rifampicin resistance (3 studies, 130 children). Seventeen studies (74%) took place in countries with a high tuberculosis burden. Overall, risk of bias and applicability concerns were low. Detection of pulmonary tuberculosis (microbiological reference standard) Sputum (11 studies) Xpert Ultra summary sensitivity was 75.3% (95% CI 68.9% to 80.8%; 345 children; moderate-certainty evidence), and specificity was 95.9% (95% CI 92.3% to 97.9%; 2645 children; high-certainty evidence). Gastric aspirate (12 studies) Xpert Ultra summary sensitivity was 69.6% (95% CI 60.3% to 77.6%; 167 children; moderate-certainty evidence), and specificity was 91.0% (95% CI 82.5% to 95.6%; 1792 children; moderate-certainty evidence). Stool (10 studies) Xpert Ultra summary sensitivity was 68.0% (95% CI 50.3% to 81.7%; 255 children; moderate-certainty evidence), and specificity was 98.2% (95% CI 96.3% to 99.1%; 2630 children; high-certainty evidence). Nasopharyngeal aspirate (6 studies) Xpert Ultra summary sensitivity was 46.2% (95% CI 34.9% to 57.9%; 94 children; moderate-certainty evidence), and specificity was 97.5% (95% CI 95.1% to 98.7%; 1259 children; high-certainty evidence). Xpert Ultra sensitivity was lower against CRS than against MRS for all specimen types, while the specificities were similar. Extrapulmonary tuberculosis Meta-analysis was not possible for lymph node tuberculosis and tuberculous meningitis due to low study numbers. Interpretation of results For a population of 1000 children, where 100 have pulmonary tuberculosis: In sputum: • 112 would be Xpert Ultra positive, of whom 75 would have pulmonary tuberculosis (true positives) and 37 would not (false positives). • 888 would be Xpert Ultra negative, of whom 863 would not have pulmonary tuberculosis (true negatives) and 25 would have pulmonary tuberculosis (false negatives). In gastric aspirate: • 151 would be Xpert Ultra positive, of whom 70 would have pulmonary tuberculosis (true positives) and 81 would not (false positives). • 849 would be Xpert Ultra negative, of whom 819 would not have pulmonary tuberculosis (true negatives) and 30 would have pulmonary tuberculosis (false negatives). In stool: • 85 would be Xpert Ultra positive, of whom 68 would have pulmonary tuberculosis (true positives) and 17 would not (false positives). • 915 would be Xpert Ultra negative, of whom 883 would not have pulmonary tuberculosis (true negatives) and 32 would have pulmonary tuberculosis (false negatives). In nasopharyngeal aspirate: • 68 would be Xpert Ultra positive, of whom 46 would have pulmonary tuberculosis (true positives) and 22 would not (false positives). • 932 would be Xpert Ultra negative, of whom 878 would not have pulmonary tuberculosis (true negatives), and 54 would have pulmonary tuberculosis (false negatives). Detection of rifampicin resistance Three studies with 76 children evaluated detection of rifampicin resistance (sputum only); two of these studies reported no cases and one reported rifampicin resistance in two children.
Xpert Ultra sensitivity was moderate in sputum, gastric aspirate, and stool specimens. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both MRS and CRS. We were unable to determine the accuracy of Xpert Ultra for detecting tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance due to a paucity of data.
This update was funded through WHO.
The protocol for this review was originally published through Cochrane in 2019. The protocol for this update was a generic protocol that consolidated previously published Cochrane protocols of Xpert Ultra for tuberculosis detection and can be accessed at https://osf.io/26wg7/. Protocol (2019) DOI: 10.1002/14651858.CD013359 Original review (2020) DOI: 10.1002/14651858.CD013359.pub2 Review update (2022) DOI: 10.1002/14651858.CD013359.pub3.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Modeling the Role of Baseline Risk and Additional Study-Level Covariates in Meta-Analysis of Treatment Effects.3 weeks agoThe relationship between the treatment effect and the baseline risk is a recognized tool to investigate the heterogeneity of treatment effects in meta-analyses of clinical trials. Since the baseline risk is difficult to measure, a proxy is adopted, which is based on the rate of events for the subject under the control condition. The use of the proxy in terms of aggregated information at the study level implies that the data are affected by measurement errors, a problem that the literature has explored and addressed in recent years. This paper proposes an extension of the classical meta-analysis with baseline risk information, which includes additional study-specific covariates other than the rate of events to explain heterogeneity. Likelihood-based inference is carried out by including measurement error correction techniques necessary to prevent unreliable inference due to the measurement errors affecting the covariates summarized at the study level. Within-study covariances between risk measures and the covariate components are computed using Taylor expansions based on study-level covariate subgroup summary information. When such information is not available and, more generally, in order to reduce computational difficulties, a pseudo-likelihood solution is developed under a working independence assumption between the observed error-prone measures. The performance of the methods is investigated in a series of simulation studies under different specifications for the sample size, the between-study heterogeneity, and the underlying risk distribution. They are applied to a meta-analysis about the association between COVID-19 and schizophrenia.Chronic respiratory diseaseAccessCare/ManagementAdvocacy
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Challenges and Possibilities in Preventing Emerging Infectious Diseases in Long-Term Care: A Qualitative Descriptive Study.3 weeks agoEmerging infectious diseases pose significant risks to vulnerable populations, particularly older adults with underlying health conditions living in long-term care institutions. Yet, while the experiences of healthcare workers in managing these crises are invaluable, there remains limited research on the specific challenges they faced.
To explore the experiences of long-term care workers-including nurses, nursing assistants, and managers-in preventing emerging infectious diseases, the challenges they faced during the pandemic, and how they addressed them.
Twelve participants from long-term care institutions in Taiwan (including assisted living facilities, residential care homes, and nursing homes) were recruited via purposive sampling. All participants worked in the sector during the COVID-19 pandemic, were actively involved in clinical care or institutional management, and were proficient in Mandarin. In-depth interviews were conducted face-to-face between July and August 2024, and data interpretation was guided by thematic analysis.
Four themes emerged. Two themes depicting challenges illustrate challenges arising from inadequate preparation, including technical, cultural, and communication barriers, noncompliance among family members, resource shortages, and the physical and emotional strain endured by frontline workers balancing duty with feelings of guilt and anxiety. Two other themes representing the possibilities for strengthening long-term care highlight the importance of ongoing education, simulation-based training, and fostering participation, as well as the need for adaptive surveillance and tailored crisis response plans.
Long-term care workers reported systemic vulnerabilities, including inadequate preparation, communication barriers, and emotional strain. They also emphasized the importance of inclusive training, simulation-based practice, and adaptive response strategies.
Long-term care institutions should strengthen preparedness by incorporating multilingual, simulation-based infection prevention training, developing family communication strategies that balance clear rationales with dialog, establishing routine surveillance with adaptive response plans, and ensuring psychosocial support for their workforce.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Gender budgeting in the post-pandemic period: an analysis in the context of health and safety of women in India.3 weeks agoIndian women suffered disproportionately due to the COVID-19 pandemic, with the loss of livelihoods, a steep increase in care work due to lockdowns, and the presence of a deeply patriarchal society that expects women to shoulder the brunt of unpaid domestic labor, as well as increasing incidents of violence. This study analyzes whether the post-COVID gender budgets in India adequately responded to the needs of women highlighted by the pandemic. We examine the six most recent gender budgets of the Government of India to analyze whether appropriate changes were introduced, keeping in mind the impact of COVID-19 on women. We find minimal changes in allocations, with only a slight increase in total allocations over the last two budgets, despite alterations within budget allocations. We find that the bulk of the allocations in the gender budget are limited to a few key ministries, with the main focus of the gender budget having been on rural development, housing, education, livelihoods, health, and nutrition. We also analyzed health, employment, and empowerment indicators for women to examine whether there have been improvements in these areas, and found that while some of the basic health indicators have improved, labor force participation rates and political empowerment of women have declined. We conclude that to actually make a difference to the status of women, one has to go beyond mere participation statistics and look at the needs, concerns, and challenges faced by women. Policymakers need to work with communities and grassroots organizations that work closely with and represent women. A top-down approach with routine budget allocations under the gender budget umbrella might, in fact, do a disservice to the cause by bringing in complacency, which India can ill afford.Chronic respiratory diseaseAccessAdvocacy
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Class-acquired influenza is more severe than non-class-acquired influenza: a survey for multi-school teachers.3 weeks agoDuring the influenza season, teachers have a higher infection rate of influenza than the general population. However, there has been no study on the clinical characteristics of this specific influenza in infection type-"class-acquired influenza," which means teachers acquire influenza infection from exposure to a substantial quantity of influenza virus aerosols in enclosed classrooms by teaching activities in a short period of time.
In this study, teachers who had suffered from influenza during the 2024-2025 Seasonal Influenza from 12 schools in Xi'an, a city in northern China, were retrospectively collected through a questionnaire. They were divided into a class-acquired influenza group and a non-class-acquired influenza group, and then compared the clinical features and effects between these two groups.
Class-acquired cases showed higher incidence of symptoms, such as fever, cough, malaise, abdominal pain and diarrhea, and showed greater severity of symptoms like dry throat, runny nose and sputum. The class-acquired influenza group had longer recovery time [7.0 (5.0, 14.0) vs. 6.5 (5.0, 10.0) days, p = 0.003], and required more medical visits (69.9% vs. 52.3%, p = 0.004), medication (74.7% vs. 62.4%, p = 0.035), and sick leave (47.9% vs. 28.4%, p < 0.001). Incubation period (onset) showed no difference (p = 0.245).
Class-acquired influenza is a specific type in teachers. Compared to non-class-acquired influenza, it involves worse symptoms, longer duration, higher healthcare needs, and more absenteeism, likely related to the unique working conditions and environment. Therefore, during the influenza season, schools and teachers should focus on rational prevention, early diagnosis and medication.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
A Systematic Review of Ocular Complications Following Different Types of Covid-19 Vaccines.3 weeks agoMore than 6 million deaths from the novel coronavirus, the Coronavirus disease 2019 (COVID-19) infection, have prompted the development of several prophylactic vaccines of COVID-19. This systematic review summarizes the ocular complications of various COVID-19 vaccinations, diseases diagnosed, treatment, and risk factors.
The search was done in PubMed, Web of Science (WOS), and Google Scholar databases. Manifestations were classified depending on the type of vaccines and the interval between vaccination and the onset of symptoms. Other data such as patients' age, gender, underlying diseases, and follow-up data were also extracted.
Initially, 10,242 articles were identified and 76 articles were eligible that among them 107 cases were reported. Ocular complications were diagnosed more often in Pfizer-BioNTech COVID-19 vaccine and Oxford-AstraZeneca COVID-19 vaccine (AstraZeneca) recipients than in others.
This systematic review highlights a wide range of ocular complications reported after COVID-19 vaccination, the most common of which is uveitis. While most cases were mild and self-limiting, some involved reactivation of preexisting inflammatory diseases. These findings emphasize the importance of postvaccination ocular surveillance. This is particularly important in individuals with a history of ocular inflammation and suggests a potential immunological mechanism that requires further investigation.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Airway Abnormalities in Children Operated for Congenital Heart Disease: Clinical characteristics and risk factors from a case-control study.3 weeks agoCongenital heart disease (CHD) is the most common congenital defect, with airway abnormalities (AAs) representing significant comorbidities that contribute to increased morbidity and clinical complexity. This study aimed to identify the most common AAs, associated risk factors, and clinical outcomes in children with CHD.
This case-control study included children aged under 13 years with CHD who underwent cardiothoracic surgery between 1 January 2016 and 31 December 2018 at the National Genetic Centre in Oman. Cases were children with concurrent AAs, while controls were age- and gender-matched children with CHD but without AAs.
The prevalence of concomitant AAs in children with CHD in the cohort was 5.5%. The most common AAs were vascular compressions (47.4%), followed by airway malacia (23.1%). Chest computed tomography was the most frequently utilised diagnostic modality. Prematurity was significantly more common among children with AAs (odds ratio: 3.2, 95% confidence interval: 1.1-11.1; P = 0.016), and the duration of invasive ventilation was significantly longer (P = 0.013).
AAs are important comorbidities in children with CHD. This study highlights the need for increased clinical vigilance and early investigation of AAs in this population. Prospective studies are warranted to further assess the long-term implications of these findings.Chronic respiratory diseaseCardiovascular diseasesAccessCare/ManagementAdvocacy