Daily Respiratory Research Analysis
A multicenter randomized trial (RESCUE-3) found that temporary transvenous diaphragm neurostimulation increases the probability of successful weaning from mechanical ventilation, though with a possible rise in serious adverse events. A Cochrane systematic review showed that parallel testing of respiratory and stool LC‑aNAATs improves sensitivity for pediatric tuberculosis, with added LF‑LAM further increasing sensitivity in children with HIV at a specificity cost. A decision model projected that
Summary
A multicenter randomized trial (RESCUE-3) found that temporary transvenous diaphragm neurostimulation increases the probability of successful weaning from mechanical ventilation, though with a possible rise in serious adverse events. A Cochrane systematic review showed that parallel testing of respiratory and stool LC‑aNAATs improves sensitivity for pediatric tuberculosis, with added LF‑LAM further increasing sensitivity in children with HIV at a specificity cost. A decision model projected that new RSV immunizations already averted hospitalizations in 2023–2024 and could prevent substantially more with higher, earlier uptake.
Research Themes
- Ventilator weaning and diaphragm-targeted neuromodulation
- Non-invasive pediatric tuberculosis diagnostics using parallel LC-aNAAT and LF-LAM
- Population-level impact modeling of RSV immunization strategies
Selected Articles
1. Temporary Transvenous Diaphragm Neurostimulation for Weaning from Mechanical Ventilation (RESCUE-3).
In an international randomized trial of difficult-to-wean patients, twice-daily transvenous diaphragm neurostimulation increased 30-day weaning success (70% vs 61%; adjusted HR 1.34) and shortened ventilation by 2.5 days. Serious adverse events were more frequent in the stimulation group.
Impact: This RCT addresses a major barrier in critical care—failure to wean—and tests a mechanistically-targeted intervention with clinically meaningful endpoints.
Clinical Implications: Consider transvenous diaphragm neurostimulation as an adjunct in patients failing multiple weaning attempts, balancing potential weaning benefits against higher serious adverse events. Implementation requires careful patient selection, procedural expertise, and safety monitoring.
Key Findings
- 30-day weaning success: 70% (treatment) vs 61% (control); adjusted HR 1.34 (95% CrI 1.01–1.78), posterior probability of superiority 97.9%
- Ventilation duration reduced by a mean of 2.5 days (95% CrI −5.0 to 0.1), posterior probability of superiority 97.1%
- Serious adverse events occurred in 36% vs 24% (treatment vs control)
- 30-day mortality 9.8% vs 10.5%; adjusted HR 0.74 (95% CrI 0.37–1.46)
Methodological Strengths
- International, multicenter randomized design with prespecified Bayesian primary analysis
- Use of prior information with downweighting and clinically relevant endpoints (weaning success, ventilation duration)
Limitations
- Open-label design and early trial termination may bias estimates
- Higher serious adverse events in the treatment arm; limited sample size reduces precision
Future Directions: Define optimal patient selection, stimulation protocols, and safety mitigation; conduct larger, fully enrolled RCTs and cost-effectiveness analyses to inform guideline adoption.
2. Parallel use of low-complexity automated nucleic acid amplification tests on respiratory and stool samples with or without lateral flow lipoarabinomannan assays to detect pulmonary tuberculosis disease in children.
Across 14 studies, parallel LC‑aNAAT testing of respiratory and stool samples increased sensitivity for pediatric TB compared with single-specimen LC‑aNAAT, with minor specificity losses. In children with HIV, adding urine LF‑LAM to parallel LC‑aNAAT further raised sensitivity but reduced specificity.
Impact: Provides high-quality, practice-informing evidence that non-invasive, parallel molecular testing improves pediatric TB detection, with clear trade-offs for HIV-positive children.
Clinical Implications: In pediatric TB workups, consider parallel LC‑aNAAT on respiratory and stool samples to increase case detection, particularly where sputum is difficult. In children with HIV, add LF‑LAM to maximize sensitivity, anticipating lower specificity and tailoring decisions to local prevalence.
Key Findings
- Without HIV: parallel respiratory+stool LC‑aNAAT pooled sensitivity 79.9% (95% CrI 67.9–89.8) and specificity 93.4% (95% CrI 87.2–97.0)
- Versus respiratory LC‑aNAAT alone: +7.1 percentage points sensitivity; −1.7 percentage points specificity
- With HIV: parallel LC‑aNAAT sensitivity 70.2% and specificity 95.4%; adding LF‑LAM increases sensitivity to 77.6% with specificity 83.9%
- Adding LF‑LAM to parallel LC‑aNAAT in HIV-positive children: +6.9 pp sensitivity; −10.2 pp specificity
Methodological Strengths
- Cochrane-standard systematic review with Bayesian bivariate random-effects meta-analysis
- Rigorous bias assessment (QUADAS‑2/‑C) and GRADE certainty ratings; evaluation against MRS and CRS
Limitations
- Heterogeneity in populations/tests and some low-certainty estimates
- CRS analyses risk incorporation bias; specificity trade-offs may vary by prevalence
Future Directions: Prospective implementation studies integrating parallel LC‑aNAAT±LF‑LAM into diagnostic algorithms, cost-effectiveness analyses, and optimization by setting-specific TB prevalence.
3. Scenario Projections of Respiratory Syncytial Virus Hospitalizations Averted Due to New Immunizations.
Using a calibrated transmission model for King County, WA, new RSV immunizations averted an estimated 125 hospitalizations in 2023–2024, with largest benefits in infants <6 months and adults ≥75 years. High early-season coverage could reduce hospitalizations by nearly 70% in young infants and ~30% in older adults; catch-up nirsevimab boosts protection in 6–11 months.
Impact: Offers timely, policy-relevant projections that quantify the benefits of early and broad uptake of RSV immunizations, informing allocation and timing strategies.
Clinical Implications: Health systems should secure early-season supply and prioritize high coverage in infants (nirsevimab plus maternal vaccination) and adults ≥75 years, with catch-up dosing for 6–11 months. Monitor waning in older adults to plan revaccination.
Key Findings
- Estimated 125 (95% PI 77–192) RSV hospitalizations averted in 2023–2024
- Infants <6 months: 28.6% (95% PI 26.9%–30.5%) reduction; adults ≥75: 14.8% (95% PI 14.3%–15.5%) reduction
- High-coverage 2024–2025 scenario projects 68.8% reduction in infants <6 months and 29.8% in adults ≥75
- Catch-up nirsevimab early in season increases 6–11 months averted hospitalizations from 31.7% to 40.4%
- Assumed 50% waning in ≥75 years reduces projected benefit to 22.2%
Methodological Strengths
- Transmission model calibrated to observed hospitalization data with projection intervals
- Scenario analyses including coverage, catch-up strategies, and waning immunity
Limitations
- Model-based estimates depend on assumptions and local calibration, limiting generalizability
- Limited product availability in 2023–2024 constrains realized impact
Future Directions: Extend to multi-region analyses, integrate real-world uptake and effectiveness data, and evaluate optimal revaccination intervals for older adults.