A critical analysis of the CFD-DEM simulation of pharmaceutical aerosols deposition in upper intra-thoracic airways: Considerations on air flow.

A well-corroborated numerical methodology ensuring reproducibility in the modeling of pharmaceutical aerosols deposition in the respiratory system via CFD-DEM simulations within the RANS framework is currently missing. Often, inadequately clarified assumptions and approximations and the lack of evidences on their quantitative impact on the simulated deposition phenomenology, make a direct comparison among the different theoretical studies and the limited number of experiments a very challenging task. Here, with the ultimate goal of providing a critical analysis of some crucial computational aspects of aerosols deposition, we address the issues of velocity fluctuations propagation in the upper intra-thoracic airways and of the persistence of secondary flows using the SimInhale reference benchmark. We complement the investigation by describing how methodologies used to drive the flow through a truncated lung model may affect numerical results and how small discrepancies are observed in velocity profiles when comparing simulations based on different meshing strategies.

A critical analysis of the CFD-DEM simulation of pharmaceutical aerosols deposition in extra-thoracic airways.

Recent advances in the characterization of the human respiratory system and in multi-phase flow dynamics in complex geometries have led numerical simulations to play an expanding role for exploring aerosol deposition mechanisms in the lungs. However, the development of an efficient numerical and mathematical description is far from unique, and determining which aspects of the modelling are critical and which details are essentially irrelevant is indeed a difficult task. With the aim of addressing this lack of a rationalized framework, we propose a systematic analysis of pharmaceutical aerosols deposition in the extra-thoracic airways, focusing on several important modelling aspects whose related assumptions and approximations have not always been sufficiently discussed and clarified. We consider the importance of intrinsic time dependent fluctuations of the air flow, highlighting how their contribution in aerosol deposition is as important as the particle-turbulence interaction one. We show how sensitive the turbulence intensity can be to the meshing strategy and how aerosol deposition can be influenced by the latter choice. We demonstrate how a swirling air jet can enhance extra-thoracic deposition compared to a straight one, and how different the deposition patterns can be in case a realistic inhalation profile and aerosol plume are employed.

[Multicentre study of comparative efficacy of meropenem and combined regimens for empirical antibacterial therapy of severe nosocomial infections: results of clinical and pharmacoeconomic analysis].

Adequacy and effectiveness of empirical antibacterial therapy of severe nosocomial infections with meropenem vs. combined regimens of antibacterial therapy were investigated and the ratio of the cost and effectiveness of the compared regimens was evaluated. A prospective, randomized, open, comparative study of two initiative regimens of empirical antibacterial therapy of severe nosocomial infections was performed: meropenem in a daily dose of 1.5-3 g and the standard regimen with the use of betalactams and fluoroquinolones in combination with aminoglycosides and/or metronidazole. Patients with recorded diagnosis of nosocomial pneumonia (including the ventilator-associated one) or abdominal infection with the signs of severe sepsis and severity of APACHE II > 14 were enrolled. The patients were stratified into 2 groups subject to the disease severity, i.e. APACHE II 15-20 and APACHE II 21-25. One hundred thirty five out of 166 patients with recorded nosocomial infection were included into the final estimate of the therapy adequacy and effectiveness (Protocol Analysis): 62 patients were treated with meropenem and in the treatment of 73 patients the standard antibacterial therapy was used. In the group of the patients treated with meropenem there were stated significantly higher clinical effectiveness (recovery in 80.6% of the patients vs. the control of 46.6%, p < 0.01) and pathogen eradication (89.6 and 48.1% respectively, p < 0.01). The difference in the clinical and bacteriological effectiveness of meropenem and the standard therapy was more evident in the subgroups of more severe patients (APACHE > 20). With the use of meropenem the probability of recovery from nosocomial infection was significantly higher (RR 1.73-1.94, p < 0.001) vs. the control. Meropenem provided significantly higher eradication of the pathogens: P. aeruginosa (88 and 40% respectively, p = 0.007), E. coli (100 and 46.7%, p = 0.003), Acinetobacter spp. (90.9 and 40%, p = 0.02). The antibacterial therapy with the use of meropenem was assessed as adequate in 51 out of 56 patients (91.1%), that was 3 times as frequent as with the use of the standard antibacterial therapy (33.9%). The cost-effectiveness coefficient with the use of meropenem was 2.2 times lower vs. the control. Therefore, the empirical therapy of severe nosocomial infections with meropenem proved to be more adequate and from the economic viewpoint more advantageous vs. the standard combined regimens of antibacterial therapy, that was evident from significantly higher clinical and bacteriological efficacy of the treatment and decrease of the terms of the patients hospitalization in intensive care units (on the average by 5 days).

[Programmed cleansing of abdominal cavity in postoperative generalized suppurative peritonitis]. / Programmirovannye sanatsii briushnoi polosti pri posleoperatsionnom rasprostranennom gnoinom peritonite.

Programmed cleansing of the abdominal cavity was performed in 54 patients in the management of postoperative generalized purulent peritonitis. Indications for stage inspection of the abdomen in different variants are discussed. The results were best in the group of patients (42 cases) treated by programmed relaparotomy and poor in patients (10 cases) in whom laparostomy had to be established. Total mortality in the analysed group was 46.3%. Polyorganic insufficiency was the main cause of death.

[Endoscopic hemostasis in pulmonary hemorrhage]. / Endoskopicheskii gemostaz pri legochnom krovotechenii.

As the result of applying endoscopic occlusion of the bronchus in complex treatment of 95 patients with pulmonary, predominantly massive, hemorrhage recovery was achieved in 77.9% of cases. Twenty-one patients died. Hemorrhage was the direct cause of death of 5 patients, 16 patients died from advancement of the principal disease, background conditions, and complications of the postoperative period not associated with pulmonary bleeding.