INTRODUCTION: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.METHODS: PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.FINDINGS: Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent class analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO2, pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0·10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0·016) and more frequent venous thrombotic events (109 [32%] of 336 patients vs 176 [26%] of 671 patients; p=0·048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1·64, 95% CI 1·17-2·29 for ventilatory ratio; 1·82, 1·24-2·66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4·65, 95% CI 1·87-11·6 for ventilatory ratio in replication cohort 1; 1·89, 1·05-3·37 for ventilatory ratio in replication cohort 2).INTERPRETATION: At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality.
OBJECTIVE: Juvenile dermatomyositis (DM) is an inflammatory myopathy in which the immune system targets the microvasculature of the skeletal muscle and skin, leading to significant muscle weakness and exercise intolerance, although the precise etiology is unknown. The goal of this study was to investigate the changes in exercise capacity in children with myositis during active and inactive disease periods and to study the responsiveness of exercise parameters.METHODS: Thirteen children with juvenile DM (mean+/-SD age 11.2+/-2.6 years) participated in this study. Patients performed a maximal exercise test using an electronically braked cycle ergometer and respiratory gas analysis system. Exercise parameters were analyzed, including peak oxygen uptake (VO2peak), peak work rate (Wpeak), and ventilatory anaerobic threshold (VAT). All children were tested during an active period of the disease and during a remission period. From these data, 4 different response statistics were calculated.RESULTS: The children performed significantly better during a remission period compared with a period of active disease. Most exercise parameters showed a very large response. The 5 most responsive parameters were Wpeak, Wpeak (percent predicted), oxygen pulse, VO2peak, and power at the VAT.CONCLUSION: We found in our longitudinal study that children with active juvenile DM had significantly reduced exercise parameters compared with a remission period. Moreover, we found that several parameters had very good responsiveness. With previously established validity and reliability, exercise testing has been demonstrated to be an excellent noninvasive instrument for the longitudinal followup of children with myositis.
IntroductionMechanical power of ventilation, a summary parameter reflecting the energy transferred from the ventilator to the respiratory system, has associations with outcomes. INTELLiVENT–Adaptive Support Ventilation is an automated ventilation mode that changes ventilator settings according to algorithms that target a low work–and force of breathing. The study aims to compare mechanical power between automated ventilation by means of INTELLiVENT–Adaptive Support Ventilation and conventional ventilation in critically ill patients.Materials and methodsInternational, multicenter, randomized crossover clinical trial in patients that were expected to need invasive ventilation > 24 hours. Patients were randomly assigned to start with a 3–hour period of automated ventilation or conventional ventilation after which the alternate ventilation mode was selected. The primary outcome was mechanical power in passive and active patients; secondary outcomes included key ventilator settings and ventilatory parameters that affect mechanical power.ResultsA total of 96 patients were randomized. Median mechanical power was not different between automated and conventional ventilation (15.8 [11.5–21.0] versus 16.1 [10.9–22.6] J/min; mean difference –0.44 (95%–CI –1.17 to 0.29) J/min; P = 0.24). Subgroup analyses showed that mechanical power was lower with automated ventilation in passive patients, 16.9 [12.5–22.1] versus 19.0 [14.1–25.0] J/min; mean difference –1.76 (95%–CI –2.47 to –10.34J/min; P < 0.01), and not in active patients (14.6 [11.0–20.3] vs 14.1 [10.1–21.3] J/min; mean difference 0.81 (95%–CI –2.13 to 0.49) J/min; P = 0.23).ConclusionsIn this cohort of unselected critically ill invasively ventilated patients, automated ventilation by means of INTELLiVENT–Adaptive Support Ventilation did not reduce mechanical power. A reduction in mechanical power was only seen in passive patients.Study registrationClinicaltrials.gov (study identifier NCT04827927), April 1, 2021URL of trial registry recordhttps://clinicaltrials.gov/study/NCT04827927?term=intellipower&rank=1
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