METHODS: A stochastic model of Ers is integrated into the VENT protocol from previous works to develop the SiVENT protocol, to account for both intra- and inter-patient variability. A cohort of 20 virtual MV patients based on retrospective patient data are used to validate the performance of this method for volume-controlled (VC) ventilation. A performance evaluation was conducted where the SiVENT and VENT protocols were implemented in 1080 instances each to compare the two protocols and evaluate the difference in reduction of possible MV settings achieved by each.
RESULTS: From an initial number of 189,000 possible MV setting combinations, the VENT protocol reduced this number to a median of 10,612, achieving a reduction of 94.4% across the cohort. With the integration of the stochastic model component, the SiVENT protocol reduced this number from 189,000 to a median of 9329, achieving a reduction of 95.1% across the cohort. The SiVENT protocol reduces the number of possible combinations provided to the user by more than 1000 combinations as compared to the VENT protocol.
CONCLUSIONS: Adding a stochastic model component into a model-based approach to selecting MV settings improves the ability of a decision support system to recommend patient-specific MV settings. It specifically considers inter- and intra-patient variability in respiratory elastance and eliminates potentially harmful settings based on clinically recommended pressure thresholds. Clinical input and local protocols can further reduce the number of safe setting combinations. The results for the SiVENT protocol justify further investigation of its prediction accuracy and clinical validation trials.
METHODS: We prospectively recruited all neonates who had CDH repair in four hospitals in Malaysia from June 2018 to October 2020. Intra vesical pressure was used as a proxy for IAP and was measured for 5 consecutive days post surgery. The daily median value was used for analysis. We categorized IAP as <11 mmHg (no IAH), 11-15 mmHg (IAH), and >15 mmHg (severe IAH). Incidence of IAH, its effects on the duration of ventilatory support, and gastrointestinal function were studied.
RESULTS: There were 24 neonates included in this study. They were operated between day 1 and 6 of life (median: 4 days old). IAH was detected within the first 3 days post surgery, with 83% occurring on day one. Those requiring ventilatory support for more than 3 days contributed the largest proportion of IAH (n = 17, 71%). There was strong correlation between days of IAH and duration of ventilation (p
METHODS: In this paper, we highlight a review of the studies that have used biomarkers to understand the association between air particles exposure and the development of respiratory problems resulting from the damage in the respiratory system. Data from previous epidemiological studies relevant to the application of biomarkers in respiratory system damage reported from exposure to air particles are also summarized.
RESULTS: Based on these analyses, the findings agree with the hypothesis that biomarkers are relevant in linking harmful air particles concentrations to increased respiratory health effects. Biomarkers are used in epidemiological studies to provide an understanding of the mechanisms that follow airborne particles exposure in the airway. However, application of biomarkers in epidemiological studies of health effects caused by air particles in both environmental and occupational health is inchoate.
CONCLUSION: Biomarkers unravel the complexity of the connection between exposure to air particles and respiratory health.
METHODS: Two stochastic models (SM2 and SM3) were developed using retrospective patient respiratory elastance (Ers) from two clinical cohorts which were averaged over time intervals of 10 and 30 min respectively. A stochastic model from a previous study (SM1) was used to benchmark performance. The stochastic models were clinically validated on an independent retrospective clinical cohort of 14 patients. Differences in predictive ability were evaluated using the difference in percentile lines and cumulative distribution density (CDD) curves.
RESULTS: Clinical validation shows all three models captured more than 98% (median) of future Ers data within the 5th - 95th percentile range. Comparisons of stochastic model percentile lines reported a maximum mean absolute percentage difference of 5.2%. The absolute differences of CDD curves were less than 0.25 in the ranges of 5 systems, providing guided, personalised, and safe MV treatment.
METHODOLOGY/PRINCIPAL FINDINGS: We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep. The experimental design featured sequential studies in the same animals over the course of a week and yielded data relating to the response at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the response included the up-regulation of cell cycle genes at d1 and d3, and the latter pronounced up-regulation of extracellular matrix-related genes at d3 and d7.
CONCLUSIONS/SIGNIFICANCE: It is possible to follow the airway wall response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance.