Improved diagnostic tools for tuberculosis that are suitable for use in peripheral health centers are essential for reducing the persistent gap between estimated and notified cases. The diagnostic accuracy and usability of the MiniDock MTB test for detecting pulmonary tuberculosis is unknown.

We conducted a prospective, cross-sectional study at outpatient centers in India, Nigeria, the Philippines, South Africa, Uganda, Vietnam, and Zambia. Patients 12 years of age or older with presumptive pulmonary tuberculosis were enrolled between September 12, 2024, and March 31, 2025. Assessment with MiniDock MTB was performed with sputum swabs and tongue swabs. Diagnostic accuracy was evaluated against a sputum-culture-based reference and as compared with sputum-smear microscopy and Xpert MTB/RIF Ultra assay. Usability was assessed with a system usability scale and direct observation.

A total of 1380 participants were enrolled; 255 (18.5%) had human immunodeficiency virus infection and 226 (16.4%) had culture-confirmed tuberculosis. MiniDock MTB sensitivity was 85.7% (95% confidence interval [CI], 80.4 to 90.0) with sputum and 79.6% (95% CI, 73.8 to 84.7) with tongue swabs; specificity was greater than 97.5% for both. Results of sputum tests with MiniDock MTB closely matched those with Xpert MTB/RIF Ultra for sensitivity (difference, -2.8 percentage points; 95% CI, -6.0 to 0.5). MiniDock MTB had greater sensitivity than smear microscopy for tests of sputum (difference, 24.3 percentage points; 95% CI, 17.9 to 30.7) and tongue swabs (difference, 18.3 percentage points; 95% CI, 12.0 to 24.7). The test showed diagnostic accuracy that was consistent with World Health Organization (WHO) accuracy targets for near-point-of-care tuberculosis diagnostics (≥85% sensitivity for sputum and ≥75% for nonsputum and ≥98% specificity for both). The median score on the system usability scale (range, 0 to 100, with higher scores indicating better perceived usability) was 75 (interquartile range, 65 to 80), which indicated good usability. No adverse events related to the index test were reported.

MiniDock MTB met WHO targets for diagnostic accuracy and usability for tuberculosis detection across diverse clinical settings. (Funded by the National Institutes of Health and others; Rapid Research in Diagnostics Development for TB Network and Assessing Diagnostics at Point-of-Care for Tuberculosis ClinicalTrials.gov numbers, NCT04923958 and NCT05941052.).

Community-acquired pneumonia (CAP) remains a leading cause of hospitalization, morbidity, and mortality worldwide, particularly among older adults with multimorbidity and frailty. Despite advances in antimicrobial therapy, clinical outcomes have improved little, highlighting the need for safe, inexpensive adjunctive treatments. Vitamin C plays a critical role in immune function, redox homeostasis, and endothelial integrity, all disrupted during acute infection. Hypovitaminosis C is common in hospitalized patients with CAP and has been associated with increased disease severity, longer length of stay (LOS), and worse outcomes. However, prior randomized trials of vitamin C have produced inconsistent results, often focusing on critically ill patients with sepsis, using short treatment durations, and discontinuing therapy abruptly.

The Vitamin C in Community-Acquired Pneumonia (VitCAP) trial aims to evaluate whether high-dose oral vitamin C administered over an extended period improves clinical recovery and patient-centered outcomes in adults hospitalized with CAP.

VitCAP is a single-center, double-blind, placebo-controlled, parallel-group randomized clinical trial conducted at a tertiary hospital in Australia. Adults aged 18 years and older hospitalized with CAP will be randomized within 48 hours of admission in a 1:1 ratio to receive either oral sodium ascorbate (1 g 3 times daily for 7 days, followed by 500 mg twice daily for 30 days) or a matching placebo in addition to standard care. Randomization will be computer generated with allocation concealment via a centralized pharmacy service, and all participants, clinicians, investigators, and outcome assessors will remain blinded. The primary outcome is time to clinical stabilization, defined using standard physiological criteria. Secondary outcomes include early clinical response, symptom burden at 30 days, intensive care unit admission, need for ventilatory or vasopressor support, LOS, all-cause mortality at 30 days and 6 months, hospital readmission, health-related quality of life, and changes in inflammatory biomarkers (C-reactive protein and procalcitonin). Analyses will follow the intention-to-treat principle. The primary outcome will be analyzed using Cox proportional hazard regression adjusted for prespecified covariates, with sensitivity analyses including restricted mean survival time.

The VitCAP trial received ethics approval from the Southern Adelaide Local Health Network Human Research Ethics Committee in 2025 and funding in September 2025. Recruitment is expected to commence in 2026 and continue for 18 to 24 months. A total of 124 participants will be enrolled to provide 80% power to detect a clinically meaningful difference in time to clinical stabilization while allowing for attrition. Data analysis will follow completion of follow-up, with primary results anticipated in 2028.

The VitCAP trial is designed to address important evidence gaps by evaluating sustained oral vitamin C supplementation in hospitalized patients with CAP using clinically meaningful patient-centered outcomes. If effective, vitamin C could represent a safe, low-cost, and scalable adjunct to standard CAP management.

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12625001361493; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12625001361493.

PRR1-10.2196/91037.

The COVID-19 pandemic served as an important test case of complementing traditional public health data with nontraditional data, such as mobility traces, social media activity, and wearable data, to inform real-time decision-making. Drawing on an expert workshop and a targeted survey of epidemic modelers in Europe, this study assesses the promise and the persistent limitations of such data in pandemic preparedness and response. We distinguish between "first-mile" challenges (obstacles to accessing and harmonizing data) and "last-mile" challenges (difficulties in translating insights into actionable policy interventions). The expert workshop, convened in March 2024 in Brussels, brought together 50 participants, including public health professionals, data scientists, policymakers, and industry leaders, to reflect on lessons learned and define strategies for better integration of nontraditional data into epidemic modeling and policymaking. The accompanying survey, gathering experiences from 29 modelers, offers empirical evidence of the barriers faced by modelers during the COVID-19 pandemic and highlights areas where key data were unavailable or underused. The experiences collected through the survey and workshop resulted in ten key actions and three overarching recommendations for public entities, data providers, and stakeholders. Our findings reveal ongoing issues with data access, quality, and interoperability, as well as institutional and cognitive barriers to evidence-based decision-making. Approximately 66% of all datasets had at least one access problem, with data sharing reluctance for nontraditional sources being double that of traditional data (30% vs 15%). Only 10% of respondents reported that they could use all the data they needed. These limitations included issues related to timeliness and granularity of data, as well as issues with linkage, comparability, and biases. To overcome these hurdles, we propose a set of enabling mechanisms, including data inventories, standardization protocols, simulation exercises, data stewardship roles, and data collaboratives. For first-mile challenges, solutions focus on technical and legal frameworks for data access. For last-mile challenges, we recommend fusion centers, decision accelerator laboratories, and networks of scientific ambassadors to bridge the gap between analysis and action. We argue that realizing the full value of nontraditional data requires a sustained investment in institutional readiness, cross-sectoral collaboration, and a shift toward a culture of data solidarity. Grounded in the lessons of the COVID-19 pandemic, the study can be used to design a roadmap for using nontraditional data to confront a broader array of public health emergencies, from climate shocks to humanitarian crises.

Lack of adherence to international recommendations leads to worse outcomes. During the COVID-19 pandemic, the total number and proportion of hospitalized patients increased, consequently straining hospital care and hindering adherence.

To evaluate adherence to clinical guidelines at our center, before, during, and shortly after the COVID-19 pandemic-induced hospital strain, and its association with clinical outcomes, using a random, balanced retrospective cohort.

A balanced and randomized sample of 50 patients per year between 2019 and 2022 was drawn from electronic medical records and analyzed with multivariable and logistic regression models. The primary outcome was a composite of in-hospital death, hemodynamic decompensation within the first 7 days, and in-hospital bleeding.

The global non-adherence in our study was 45.4%. The main risk factors for non-adherence were any mortality risk classification above low-risk PE and a PESI class different from class I, with ORs of 3.47 (95% CI 2.07-5.82) and 1.57 (95% CI 1.04-2.37), respectively. In both periods (COVID-19 season and non-COVID-19 season), non-adherent management strongly correlated with the composite outcome, OR = 2.36 (95% CI, 1.23-4.54). Non-adherence was also associated with worse in-hospital outcomes, with an incidence rate of the composite outcome of 21.08 per 1000 days/person (95% CI 10.97-40.51) and 47.7 per 1000 days/person (95% CI 33.39-67.50), and an attributable risk of 1.09% (95% CI -8.47%-10.64%).

Overall, our findings highlight the need to prioritize human and material resources to ensure adherence to the standards of care for PE patients.

To explore the association between fat metabolism, frailty phenotype, and Severe Airflow Limitation（SAL） in middle-aged and elderly populations, identify non-linear thresholds and sociodemographic modification effects.

This cross-sectional study included 2,907 participants (556 SAL cases) from the China Health and Retirement Longitudinal Study (CHARLS). Associations between lipid indices (AIP, residual cholesterol, etc.), frailty index, and SAL were examined using multivariate logistic regression. Nonlinear relationships were assessed using piecewise regression with the segmented package to identify thresholds. Subgroup and interaction analyses were conducted to evaluate effect modifications by age, gender, education, and other factors.

AIP showed an inverse association with SAL (fully adjusted OR = 0.556, 95% CI: 0.394-0.787; P < 0.001). Residual cholesterol exhibited a nonlinear association with a threshold at 0.329 mmol/L: below this threshold, the inverse association was substantially stronger (OR = 0.003, 95% CI: 0.000-0.473; P = 0.024); above the threshold, the inverse association was attenuated but remained significant (OR = 0.758, 95% CI: 0.595-0.967; P = 0.026). Frailty status was positively associated with SAL (OR = 1.816, 95% CI: 1.467-2.248; P < 0.001). Education level modified the associations of AIP (interaction P = 0.036) and residual cholesterol (interaction P = 0.009), with the strongest inverse associations observed in the highest education group. Rural residents had a higher prevalence of SAL than urban residents (74.8% vs. 69.3%, P = 0.010).

In this cross-sectional study, lower AIP and residual cholesterol levels below 0.329 mmol/L, as well as frailty, were associated with SAL, particularly among older and rural populations. The observed lipid profiles may reflect disease-related metabolic alterations. The modification of lipid-SAL associations by education level suggests that social factors may be relevant for identifying high-risk populations.

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the infection resulting in lung inflammation, pulmonary vascular leakage and diffuse alveolar damage. Polymerase delta-interacting protein-2 (Poldip2) mediates lung inflammation and vascular permeability after lipopolysaccharide-induced acute respiratory distress syndrome; however, whether it also affects the pathological consequences of SARS-CoV-2 infection is completely unknown. Here, we assessed the role of Poldip2 in inflammation, immune cell infiltration and lung tissue damage in response to SARS-CoV-2. Our data show that Poldip2 expression was elevated in human lung vascular endothelium after infection. In a Poldip2-deficient heterozygous mouse model, acute clinical symptoms were not affected. However, seven days after infection, Poldip2 knockdown reduced viral load, decreased infiltration of myeloperoxidase (MPO)-positive neutrophils into inflamed lungs, and reduced tissue damage. Poldip2 also modulated the inflammatory response to viral infection in a heterogeneous manner, reflecting its diverse regulatory roles. These data support the concept that targeting Poldip2 could potentially attenuate severe lung injury following SARS-CoV-2 infection.

To estimate the incidence of tobacco use during the COVID-19 pandemic among Brazilian adults and to analyze the factors associated with initiation during this period.

A cross-sectional study using data from the ConVid 2 - Pesquisa de Comportamento (ConVid 2 - Behavior Survey), conducted between July and December 2023 through virtual chain sampling. Prevalence of tobacco use before, during, and after the COVID-19 pandemic, as well as initiation during the pandemic, were assessed. Independent variables included sociodemographic characteristics, health conditions, mental health, and lifestyle factors. Prevalences and 95% confidence intervals (95%CI) were estimated, and factors associated with initiation were investigated using multivariable logistic regression.

The prevalence of smoking was 10.35% before the pandemic, 15.88% during (with an incidence of 5.5% of new smokers), and 12.2% in the post-pandemic period. Higher odds of smoking initiation during the pandemic were observed among individuals not living with a partner (OR=1.44; 95%CI 1.06-1.95), those who self-identified as non-white (OR=2.20; 95%CI 1.17-4.13), those reporting worsening feelings of sadness (OR=1.65; 95%CI 1.11-2.44), and those reporting increased alcohol consumption (OR=6.51; 95%CI 2.89-14.61). Lower odds were found among residents of the Southeast (OR=0.33; 95%CI 0.13-0.79) and Northeast (OR=0.25; 95%CI 0.11-0.57) regions.

These findings highlight the need for public policies targeting more vulnerable populations.

Emergency department (ED) use declined drastically in the early stages of the COVID-19 pandemic. While the immediate effects of the pandemic are well-characterized, the longer term recovery patterns in ED use and regional differences in these patterns remain poorly understood. In Canada, provincial differences in public health policy responses may have influenced ED utilization during the pandemic, where Ontario implemented more restrictive and prolonged public health measures compared to Alberta, making Canada an ideal place to examine how regional variation in policy impacted ED use. Our objective in this study was to evaluate the impact of the pandemic on patterns of ED use in Ontario and Alberta and explore the potential differences in these patterns.

Our primary outcome measure was the monthly count of all-cause ED visits in Ontario and Alberta. We obtained 146 entries of monthly counts of all-cause ED visits from April 2011-May 2023 (73,690,650 ED visits in Ontario and 27,132,554 in Alberta) from 206 EDs in Ontario and 113 EDs in Alberta and conducted a retrospective, interrupted time series analysis. Negative binomial regression models were used to estimate trends before and after the pandemic onset in March 2020 in each province and to test cross-provincial differences.

Ontario and Alberta experienced immediate and statistically significant reductions in monthly ED visits following the pandemic onset by 26.9% and 27.7%, respectively. Pandemic trend showed gradual recovery in both provinces. However, by May 2023 ED volumes in Ontario remained 5.5% below the expected volume, while Alberta's exceeded it by 2.5%. Relative risk (RR) estimates confirmed significant declines in ED volumes during the pandemic in Ontario (RR = 0.64) and in Alberta (0.72). No statistically significant cross-provincial differences were observed in the immediate reduction and the speed of recovery of the ED utilization during the pandemic.

Ontario experienced a decline in ED visits followed by a steady recovery that did not reach pre-pandemic projections, raising concern for missed care. Alberta also experienced an immediate decline but demonstrated a slightly faster recovery, eventually surpassing pre-pandemic projections. Model parameters characterizing the ED use patterns in each province were not significantly different, despite differences in provincial public health policies introduced in the pandemic's early phases. Thus, broader national or individual level factors may have contributed more substantially to healthcare utilization than provincial policies during the COVID-19 pandemic.

To determine the relationship between mucus plugging and CT-derived parameters of sarcopenia in routine chest CT-scans. Patients with advanced Chronic Obstructive Lung Disease (COPD GOLD 3 or 4) were investigated. Mucus plug score (MPS) and cross-sectional muscle area (CSA) of pectoralis and erector spinae muscle of each patient was assessed by two radiologists. Statistics included non-parametric group comparison, multivariate analysis, and inter- and intrarater agreement. Median age of 123 patients (47 female) was 66 years. In 63 patients (15 females) no mucus plugging was found. 31 patients (15 females) had 1-2 mucus plugs and 29 patients (17 females) had a mucus plug of ≥ 3. PM_CSA and ESM_CSA were not independently associated with MPS; however, the association between PM_CSA and MPS was modified by body weight, with a significant negative correlation between body weight and PM_CSA in patients with higher MPS (≥ 3). Inter- and intrarater agreement was very good (ICC 0.899 or higher). Imaging based evaluation of MPS and CSA is reliable on routine chest CT-scans. Patients with more advanced COPD exhibited a higher MPS and larger PM_CSA relative to body weight, possibly due to the greater muscular effort required for breathing.

Viral isolates consist of complex mixtures of many variants that are termed mutant spectra, distributions, clouds or swarms. They include information on virus behavior that is not captured by consensus sequences. Here, we describe experimental procedures, a bioinformatics pipeline, and calculations to characterize the mutant spectrum of RNA viruses. The data are obtained through the high-resolution MiSeq Illumina ultra-deep sequencing platform. We describe protocols for SARS-CoV-2 patients' isolates and laboratory populations, which can be adapted to other RNA viral pathogens. Precautions for sample handling to avoid cross-contaminations and controls for mutation and deletion detection reliability are also outlined.