Clarithromycin is an effective immunomodulator when administered late in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa

BACKGROUND: To apply clarithromycin as an immunomodulatory treatment in experimental urosepsis by multidrug-resistant Pseudomonas aeruginosa. METHODS: Acute pyelonephritis was induced in 40 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of sepsis in four groups: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. Survival and vital signs were recorded; blood was sampled for culture and estimation of pro-inflammatory mediators; monocytes were isolated for determination of apoptotic rate and ex vivo TNFα secretion. Quantitative cultures and biopsies of organs were performed after death. RESULTS: Increased rectal temperature and oxygen saturation were found in groups B and D compared to A and C. Mean survival of groups A, B, C and D was 2.65, 7.15, 4.25 and 8.70 days respectively. No differences were noted between groups concerning bacterial load in blood and tissues and serum endotoxins. Serum MDA and total caspase-3 activity of monocytes of group D decreased following treatment compared to other groups. Negative correlation was detected between cytoplasmic caspase-3 and ex vivo secretion of TNFα of blood monocytes of group A; similar correlation was not found for any other group. Pathology scores of liver and lung of group B were lower than group A. CONCLUSION: Clarithromycin administered late in experimental urosepsis by multidrug-resistant P. aeruginosa prolonged survival and ameliorated clinical findings. Its effect is probably attributed to immunomodulatory intervention on blood monocytes

Modelling the hydrodynamic response of a floating offshore wind turbine – a comparative study

This paper summarises the work conducted within the 1st FOWT (Floating Offshore Wind Turbine) Comparative Study organised by the EPSRC (UK) ‘Extreme loading on FOWTs under complex environmental conditions’ and ‘Collaborative computational project on wave structure interaction (CCP-WSI)’ projects. The hydrodynamic response of a FOWT support structure is simulated with a range of numerical models based on potential theory, Morison equation, Navier-Stokes solvers and hybrid methods coupling different flow solvers. A series of load cases including the static equilibrium tests, free decay tests, operational and extreme focused wave cases are considered for the UMaine VolturnUS-S semi-submersible platform, and the results from 17 contributions are analysed and compared with each other and against the experimental data from a 1:70 scale model test performed in the COAST Laboratory Ocean Basin at the University of Plymouth. It is shown that most numerical models can predict similar results for the heave response, but significant discrepancies exist in the prediction of the surge and pitch responses as well as the mooring line loads. For the extreme focused wave case, while both Navier–Stokes and potential flow base models tend to produce larger errors in terms of the root mean squared error than the operational focused wave case, the Navier-Stokes based models generally perform better. Given the fact that variations in the solutions (sometimes large) also present in the results based the same or similar numerical models, e.g., OpenFOAM, the study highlights uncertainties in setting up a numerical model for complex wave structure interaction simulations such as those involving a FOWT and therefore the importance of proper code validation and verification studies

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Occupational Risks: A Follow-up Method Based on Individual Work History Records Including the Environmental Aspects of the Workplace

Abstract:This article analyzes the Curriculum Laboris or career reconstruction as a means of studying the occupational risks of employees. A type of Curriculum Laboris which makes the established record easier to use has been suggested. The authors point out some advantages to be expected from the proposed computerized method. The usefulness of the proposed Curriculum Laboris is largely conditioned by lack of standards for guiding data collection by physicians. Finally, the Curriculum Laboris has been considered as an element of a larger information system.</jats:p