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.
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.
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.