Daily Respiratory Research Analysis
A phase 3 randomized trial shows onradivir, a novel PB2 polymerase inhibitor, has comparable efficacy to oseltamivir for acute uncomplicated influenza with an acceptable safety profile. A Cochrane review finds that combining low-complexity NAAT on respiratory samples with urine LF-LAM improves tuberculosis diagnosis in people with HIV at the cost of lower specificity. A meta-analysis in elderly obstructive sleep apnea indicates CPAP improves sleepiness, mood, cognition, and reduces mortality, re
Summary
A phase 3 randomized trial shows onradivir, a novel PB2 polymerase inhibitor, has comparable efficacy to oseltamivir for acute uncomplicated influenza with an acceptable safety profile. A Cochrane review finds that combining low-complexity NAAT on respiratory samples with urine LF-LAM improves tuberculosis diagnosis in people with HIV at the cost of lower specificity. A meta-analysis in elderly obstructive sleep apnea indicates CPAP improves sleepiness, mood, cognition, and reduces mortality, reinforcing adherence-focused care.
Research Themes
- Antiviral therapeutics for respiratory infections
- Optimizing tuberculosis diagnostics in people with HIV
- Long-term effectiveness of CPAP in elderly obstructive sleep apnea
Selected Articles
1. Efficacy and safety of onradivir in adults with acute uncomplicated influenza A infection in China: a multicentre, double-blind, randomised, placebo-controlled and oseltamivir-controlled, phase 3 trial.
In a multicentre, double-blind, randomized phase 3 trial (n=702 ITTI), onradivir 600 mg once daily for 5 days achieved clinical recovery comparable to oseltamivir and superior to placebo in adults with acute uncomplicated influenza A. The safety profile was acceptable, with common treatment-emergent adverse events including nasopharyngitis, headache, diarrhea, and upper respiratory tract infection.
Impact: This is a rigorously conducted phase 3 RCT of a first-in-class PB2 inhibitor, offering an alternative antiviral mechanism amid concerns for neuraminidase inhibitor resistance and variant evolution.
Clinical Implications: Onradivir can be considered a viable oral option for acute uncomplicated influenza A, with efficacy similar to oseltamivir. Health systems may benefit from diversified antiviral classes to mitigate resistance and supply constraints.
Key Findings
- Randomized, double-blind phase 3 trial across 68 sites enrolled 702 ITTI participants; 349 received onradivir, 177 oseltamivir, 176 placebo.
- Onradivir achieved time-to-alleviation of symptoms comparable to oseltamivir and superior to placebo (primary endpoint).
- Safety was acceptable: common TEAEs included nasopharyngitis (23.8%), headache (14.7%), diarrhea (14.5%), and upper respiratory tract infection (12.9%).
Methodological Strengths
- Multicentre, double-blind, randomized, placebo- and active-controlled design with ITTI analysis.
- Stratified randomization by symptom scores and standardized dosing over 5 days.
Limitations
- Trial population limited to adults 18–64 years in China with uncomplicated influenza; generalizability to severe disease, older adults, or pediatric patients is uncertain.
- Primary clinical endpoint details beyond comparative statements are not fully specified in the abstract.
Future Directions: Head-to-head trials across diverse populations (elderly, pediatric, severe influenza) and real-world effectiveness studies, including resistance surveillance and combination antiviral strategies.
BACKGROUND: Onradivir (ZSP1273) is a potent inhibitor of the PB2 subunit of influenza A virus (IAV) polymerase. Our previous, phase 2 clinical trial showed that a 600 mg regimen of onradivir initiated within 48 h of symptom onset can expedite the recovery of adult patients from acute, uncomplicated influenza. Here, we aimed to evaluate the safety and therapeutic efficacy of onradivir in a larger group with acute, uncomplicated influenza. METHODS: This randomised, double-blind, multicentre, placebo-controlled and oseltamivir-controlled, phase 3 trial was conducted at 68 clinical sites in China. Eligible participants were adults (aged 18-64 years) with an influenza-like illness who screened positive by rapid IAV antigen testing at the first clinical visit, and had a fever (axillary temperature ≥38·0°C) with at least one moderate systemic and one moderate respiratory symptom within 48 h of symptom onset. Patients were randomly assigned into three treatment groups, stratified by influenza symptom scores (≤11 or ≥12), in a 2:1:1 ratio by an interactive web response system, with each treatment lasting 5 days: 600 mg oral onradivir tablets once daily, 75 mg oral oseltamivir phosphate capsules twice daily, or oral placebo. The primary outcome was the efficacy of onradivir versus placebo in the time to alleviation of symptoms (TTAS), from treatment initiation to the remission of influenza symptoms, in the intention-to-treat infection (ITTI) population (ie, all participants who were randomly assigned and tested positive for IAV). The safety endpoints were the frequency and severity of adverse events in all participants who received treatment at least once. This trial is registered with ClinicalTrials.gov (NCT04683406) and is completed. This clinical trial was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China (EC-2020-080[YW]-02). FINDINGS: Between May 12, 2022, and May 16, 2023, 943 patients were screened, of whom 750 met the inclusion criteria and were randomly assigned to a group. 48 had negative IAV tests, resulting in an ITTI population of 702 participants (413 [59%] men and 289 [41%] women; mean age 28·1 years [SD 9·7]): 349 in the onradivir group, 177 in the oseltamivir group, and 176 in the placebo group. The baseline viral load (mean 5·15 log
2. Parallel use of low-complexity automated nucleic acid amplification tests and lateral flow urine lipoarabinomannan assays to detect tuberculosis disease in adults and adolescents living with HIV.
Across 27 studies (n=12,651), parallel testing with respiratory LC-aNAAT plus urine LF-LAM increased sensitivity versus LC-aNAAT alone (e.g., +6.7 percentage points with a microbiological reference standard) but reduced specificity (−6.8 percentage points). In high TB prevalence settings among people with HIV, the sensitivity gains likely outweigh the specificity trade-off.
Impact: This Cochrane review provides high-quality quantitative evidence to guide diagnostic algorithms for TB in people with HIV, balancing sensitivity gains with specificity losses when adding LF-LAM to LC-aNAAT.
Clinical Implications: Programs should consider parallel LC-aNAAT + LF-LAM in high-prevalence settings or in patients with advanced HIV/serious illness to improve case detection, while implementing stewardship to mitigate false positives in low-prevalence settings.
Key Findings
- Parallel LC-aNAAT (respiratory) + LF-LAM (urine) pooled sensitivity 77.5% and specificity 89.4% using microbiological reference standard (27 studies, 12,651 participants).
- Compared with LC-aNAAT alone, parallel testing increased sensitivity by 6.7 pp (95% CrI 3.8–10.7) and decreased specificity by 6.8 pp (95% CrI −9.5 to −4.7).
- Using a composite reference standard (23 studies, 11,109 participants), parallel testing improved sensitivity by 16.0 pp but reduced specificity by 3.5 pp.
Methodological Strengths
- Cochrane methodology with comprehensive searches, duplicate data extraction, and quality assessment using QUADAS-2/QUADAS-C.
- Bayesian bivariate random-effects meta-analysis with prespecified subgroup analyses.
Limitations
- Certainty of evidence for differences was low to very low for some outcomes; heterogeneity across settings and patient severity.
- Operational implications (cost, workflow, and impact on overtreatment) depend on local prevalence and health system capacity.
Future Directions: Prospective implementation studies to optimize parallel testing strategies by prevalence, CD4 strata, and care setting, including cost-effectiveness and patient-centered outcomes.
BACKGROUND: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular World Health Organization (WHO)-recommended rapid diagnostic tests (also known as mWRDs) widely used to diagnose tuberculosis disease. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended by the WHO to assist in diagnosing tuberculosis disease amongst people with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM used in isolation for the detection of tuberculosis, but in clinical practice the tests may be used in parallel (i.e. LC-aNAAT in combination with LF-LAM). OBJECTIVES: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory samples and LF-LAM on urine versus LC-aNAATs on respiratory samples alone for detection of tuberculosis disease in adults and adolescents with HIV who present with presumptive tuberculosis. SEARCH METHODS: We searched Cochrane CENTRAL, MEDLINE, Embase, Science Citation Index-Expanded, Biosis Previews, Conference Proceedings Citation Index - Science, Scopus, WHO Global Index Medicus, ProQuest Dissertations & Theses, ClinicalTrial.gov, and the WHO International Clinical Trials Registry up to 3 November 2023. SELECTION CRITERIA: We included studies that allowed assessment of the diagnostic accuracy of parallel testing and LC-aNAAT on respiratory samples in the same study group. Participants were adults and adolescents (defined as 10 years of age and older) with HIV who presented with presumptive tuberculosis. The reference standards we used for the detection of tuberculosis disease were microbiological or composite. As well as published studies, we included unpublished data if the data provided by study authors on request were the final data and could be used to compare diagnostic accuracy of parallel testing to one of the component tests. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a standardised form and assessed methodological quality using QUADAS-2 and QUADAS-C tools. We performed bivariate random-effects meta-analysis using a Bayesian approach to estimate sensitivity, specificity, and absolute differences between index tests. We performed subgroup analyses based on the presence of signs and symptoms, CD4 cell count, and clinical setting, as well as separate analyses for those with a positive screen for tuberculosis, advanced HIV, or serious illness. MAIN RESULTS: In 27 studies involving 12,651 participants, of whom 2368 (19%) had tuberculosis based on a microbiological reference standard, the parallel use of respiratory LC-aNAAT and urine LF-LAM had a pooled sensitivity of 77.5% (95% credible interval (CrI) 73.4 to 81.3) and specificity of 89.4% (95% CrI 85.8 to 92.3). Compared to respiratory LC-aNAAT alone, parallel testing had 6.7 (95% CrI 3.8 to 10.7) percentage points higher sensitivity (low certainty) and -6.8 (95% CrI -9.5 to -4.7) percentage points difference in specificity (low-certainty evidence), using a microbiological reference standard. In 23 studies, 11,109 participants, of whom 3723 (34%) had tuberculosis based on a composite reference standard, parallel testing had a pooled sensitivity of 67.6% (95% CrI 59.9 to 74.6) and a pooled specificity of 96.2% (95% CrI 92.8 to 98.1). Compared to respiratory LC-aNAAT alone, parallel testing had 16.0 (10.7 to 22.9) percentage points higher sensitivity (low-certainty evidence) and -3.5 (95% CrI -6.6 to -1.7) percentage points difference in specificity (very low certainty evidence), using a composite reference standard. AUTHORS' CONCLUSIONS: In the diagnosis of tuberculosis disease in people with HIV who present with presumptive tuberculosis, parallel testing (LC-aNAAT on respiratory samples and LF-LAM on urine) improves sensitivity at the cost of reduced specificity compared to LC-aNAAT on respiratory samples alone. The gain in sensitivity should be weighed against the loss of specificity, taking into consideration the varying tuberculosis prevalence in different settings. For low-prevalence settings, using the tests in parallel may lead to a large increase in false-positive results. In settings with high tuberculosis prevalence, the benefit of identifying additional patients with tuberculosis at the point-of-care likely outweighs the relatively lower risk of overtreatment of those without tuberculosis. FUNDING: Internal sources: Liverpool School of Tropical Medicine, UK External sources: Foreign, Commonwealth and Development Office (FCDO), UK. Project number 300342-104; WHO, TB Prevention, Diagnosis, Treatment, Care & Innovation (PCI), Global TB Programme REGISTRATION: Protocol available via https://doi.org/10.1002/14651858.CD016070, version published 13 May 2024.
3. Continuous positive airway pressure treatment for sleep apnea in elderly patients systematic review and meta-analysis.
In 13 studies with 14,880 elderly patients with moderate–severe OSA, CPAP reduced daytime sleepiness (ESS −2.92), improved anxiety and depression (effect sizes 0.2 and 0.35), modestly improved cognitive measures (digit span 0.19; digit symbol 0.24), and reduced mortality (effect size 0.64) and diurnal symptoms (0.61). Benefits were greatest in adherent users (≥4 h/night).
Impact: This meta-analysis consolidates clinically meaningful benefits of CPAP in elderly OSA, including mortality reduction, supporting adherence-focused strategies in a high-comorbidity population.
Clinical Implications: Prioritize adherence interventions (education, troubleshooting, mask fit) to achieve ≥4 h/night CPAP use in elderly OSA, with monitoring of neurocognitive and mood outcomes alongside mortality risk.
Key Findings
- Meta-analysis of 13 studies (14,880 participants) showed significant reduction in daytime sleepiness (ESS −2.92).
- Improved anxiety (effect size 0.2) and depression (0.35) and modest gains in cognitive tests (digit span 0.19; digit symbol 0.24).
- Reduced mortality (effect size 0.64) and diurnal symptoms (0.61), with benefits accentuated in users adherent ≥4 h/night.
Methodological Strengths
- Focused elderly population with moderate–severe OSA and multiple clinically relevant outcomes including mortality.
- Quantitative synthesis across multiple domains (sleepiness, mood, cognition, mortality) improving external validity.
Limitations
- Heterogeneity in study designs and adherence reporting; not all studies were randomized or compliance-controlled.
- Effect sizes and follow-up durations varied; residual confounding is possible.
Future Directions: Large, adherence-enriched RCTs in elderly OSA to confirm mortality and cognitive benefits, stratified by comorbidity profiles and device/interface optimization strategies.
BACKGROUND: The purpose of this study was to review the literature of the last 10 years (published in 2015-2024), in order to evaluate the effect of continuous positive airway pressure (CPAP) treatment on obstructive sleep apnea (OSA) among the elderly. STUDY DESIGN AND METHODS: We conducted a meta-analysis of studies evaluating CPAP vs. usual care in patients more than 65 years with moderate to severe OSA. Our outcomes were changes in ESS (Epworth Sleepiness Scale), neurocognitive tests, Sleep-related Quality of Life (QSQ), and mortality. RESULTS: We identified 229 studies from various databases, including 13 with 14,880 participants in our analysis. CPAP significantly was associated with improvement of sleepiness, anxiety and depression according to the effect size of -2.92, 0.2 and 0.35 respectively (CI: -3.82 to -2.03, 0.02 to 0.38, 0.03 to 0.67). The digit span and digit symbol were improved in the CPAP group by the small effect size of 0.19 and 0.24 respectively. (CI: 0.01 to 0.36, 0.06 to 0.41). Also mortality and diurnal symptoms were reduced with the moderate effect size of 0.64 and 0.61 respectively in the CPAP group. (CI: 0.52 to 0.75, 0.42 to 0.79). CONCLUSION: CPAP significantly impacts daytime sleepiness, sleep-related quality of life, cognitive functions, and mortality in elderly individuals. Benefits are particularly evident in consistent users over four hours, especially regarding daytime sleepiness. Larger, well-structured randomized controlled trials involving compliant patients are crucial to provide robust evidence on CPAP effects in elderly populations, considering age-related comorbidities, cognitive performance, and neuropsychological issues.