SynthesisBMJ open2016
Multivariable fractional polynomial interaction to investigate continuous effect modifiers in a meta-analysis on higher versus lower PEEP for patients with ARDS.
Synthesis in BMJ open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Investigating treatment-effect modification by a continuous covariate in IPD meta-analysis: an approach using fractional polynomials.BMC medical research methodology · 2022Pooled it
- High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome.The Cochrane database of systematic reviews · 2021Pooled it
- Beyond injury severity: monocyte-associated small extracellular vesicles distinguish respiratory-support trajectories following thoracic trauma.BMC pulmonary medicine · 2026Article
- The hospital length of stay and mortality and its risk and protective factors among patients with acute respiratory distress syndrome receiving extracorporeal membrane oxygenation: a systematic review and meta-analysis.Journal of thoracic disease · 2025Article
- EIT guided evaluation of regional ventilation distributions in neonatal and pediatric ARDS: a prospective feasibility study.Respiratory research · 2025Article
- Nonlinear effects and effect modification at the participant-level in IPD meta-analysis part 2: methodological guidance is available.Journal of clinical epidemiology · 2023Article
- Nonlinear effects and effect modification at the participant-level in IPD meta-analysis part 1: analysis methods are often substandard.Journal of clinical epidemiology · 2023Article
- Predicting personalised absolute treatment effects in individual participant data meta-analysis: An introduction to splines.Research synthesis methods · 2022Article
- Unusual Localization of Blood-Borne Loa loa Microfilariae in the Skin Depends on Microfilarial Density in the Blood: Implications for Onchocerciasis Diagnosis in Coendemic Areas.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Airway Pressure Release Ventilation Mode Improves Circulatory and Respiratory Function in Patients After Cardiopulmonary Bypass, a Randomized Trial.Frontiers in physiology · 2021Article
- Individual participant data meta-analysis to examine interactions between treatment effect and participant-level covariates: Statistical recommendations for conduct and planning.Statistics in medicine · 2020Article
- Meta-analysis of non-linear exposure-outcome relationships using individual participant data: A comparison of two methods.Statistics in medicine · 2019Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesA recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes.
settingPooled data from three randomised trials in intensive care identified by a systematic review.
participants2299 patients with acute lung injury requiring mechanical ventilation.
interventionsHigher (N=1136) versus lower PEEP (N=1163) ventilation strategy. OUTCOME MEASURES: Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure-PEEP)) and body mass index (BMI).
resultsWe found that for patients with PaO2/FiO2 below 150 mm Hg, but above 100 mm Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO2/FiO2 above 200 mm Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40 mL/cm H2O or patients with a BMI above 35 kg/m(2), we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings.
conclusionsMFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS. STUDY REGISTRATION NUMBER: CRD42012003129.
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