Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane.

BACKGROUND: The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. OBJECTIVES: To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. METHODS: A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). RESULTS: The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. CONCLUSIONS: We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

Magnetization switching and microwave oscillations in nanomagnets driven by spin-polarized currents.

A novel theoretical approach to magnetization dynamics driven by spin-polarized currents is presented. Complete stability diagrams are obtained for the case where spin torques and external magnetic fields are simultaneously present. Quantitative predictions are made for the critical currents and fields inducing magnetization switching, for the amplitude and frequency of magnetization self-oscillations, and for the conditions leading to hysteretic transitions between self-oscillations and stationary states.

Establishment of T-Helper-2 immune response based gerbil model of enteric infection.

BACKGROUND: The reciprocal antagonism of T-helper-1 (Th-1) and Th-2 type immune responses suggests that helminth parasitic infection may ameliorate disease where a Th-1 type response dominates. The Mongolian gerbil has been useful in the investigation of the pathogenesis of gastric cancer, since long-term infection of gerbils with Helicobacter pylori induces adenocarcinoma. In this study the kinetics of worm expulsion and associated immune responses in gerbils infected with Trichinella spiralis were investigated in an attempt to establish an animal model of parasitic infection that could be helpful when investigating the effect of a Th-2 type response on Th-1-based intestinal disorders. METHODS: Gerbils were infected with various doses of infective T. spiralis larvae and were euthanized on different days after infection to investigate the intestinal worm recovery, goblet cell population, eosinophil response and serum IgG1 responses. RESULTS: The number of worms recovered from the intestine was dependent on the number of larvae used for the infection. Almost all worms were expelled spontaneously by day 26 post-infection, when the gerbils had been infected with 375 or 750 larvae. The number of intestinal goblet cells, eosinophils and the serum IgG1 level significantly increased following infection compared with the control. CONCLUSION: This is the first comprehensive report on the time-course of T. spiralis infection in gerbils. The data indicate that the T. spiralis-infected gerbil could be used as a model of the Th-2-based response to investigate the effect of a parasite-induced Th-2 response on various Th-1-mediated intestinal disorders such as H. pylori-induced gastritis and gastric carcinoma.

Global predictive real-time control of Quebec Urban Community's westerly sewer network.

Quebec Urban Community (QUC) has selected Global Predictive Real-Time Control (GP-RTC) as the most efficient approach to achieve environmental objectives defined by the Ministry of Environment. QUC wants to reduce combined sewer overflows (CSOs) frequency to the St Lawrence river to two events per summer period in order to reclaim the use of Jacques-Cartier Beach for recreational activities and sports of primary contact. QUC's control scheme is based on the Certainty Equivalent Control Open Loop Feedback (CEOLF) strategy which permits one to introduce, at each control period, updated measurements and meteorological predictions. A non-linear programming package is used to find the flow set points that minimise a multi-objective (cost) function, subjected to linear equality and inequality constraints representing the physical and operational constraints on the sewer network. Implementation of GP-RTC on QUC's westerly network was performed in the summer of 1999 and was operational by mid-August. Reductions in overflow volumes with GP-RTC compared to static control are attributed to the optimal use of two existing tunnels as retention facilities as well as the maximal use of the wastewater treatment plant (WWTP) capacity.

Quality and cost-effective management of mental health care.

Corporations have reduced their mental health care benefits by limits on coverage for such services. We report on a comprehensive mental health care program, including prevention and early intervention, hospital utilization review, and consulting psychiatrist, which has improved the quality and has significantly reduced inpatient insurance psychiatric hospitalization costs. Mental health service coverage was actually enhanced. Inpatient psychiatric hospitalization costs 12 months before and after the implementation of a concurrent psychiatric hospital utilization review program were reviewed for a major corporation. Total hospital days and average length of stay decreased by 43% whereas total inpatient psychiatric hospital charges decreased by $309,518. Total inpatient days decreased by 1045. Quality and cost-effective comprehensive psychiatric health care services can be offered by major corporations providing that such benefits are carefully designed and managed.

Invasion of paranasal sinuses by Aspergillus oryzae.

A 24-year-old male patient receiving chemotherapy for acute promyelocytic leukemia developed fever, right periorbital swelling and mild right proptosis. A head scan showed opacification of the right maxillary and ethmoid sinuses with adjacent soft tissue swelling. Biopsy of the nasal mucosa demonstrated the typical septate hyphae of Aspergillus species which was later shown on culture to be Aspergillus oryzae. A. oryzae has only rarely been reported in human disease and there is confusion as to its precise identification and role. We would like to confirm the pathogenicity of A. oryzae with this uncommon presentation of aspergillosis and also emphasize the need to take adequate and multiple cultures in suspected cases so that the possibility of species identification will be maximized.

Coagulum pyelolithotomy.

The interest shown in a coagulum pyelolithotomy technique reported at a recent urologic meeting has prompted this preliminary communication. It was not possible to follow the methodology recently reported using the fibrinogen preparation available in Canada. This led to the development of the simpler technique described in this report which has been used in 3 cases to date. In all cases all calculi were easily extracted. Using the coagulum, considerable operating room time was saved and renal instrumentation was minimized.

Fatal human infection with mesocercariae of the trematode Alaria americana.

A fatal human infection with mesocercafiae of Alaria americana is described. Several thousand mesocercariae were estimated to be present in the peritoneal cavity, bronchial aspirate, brain, heart, kidney, liver, lungs, lymph nodes, pancreas, retroperitoneal adipose tissue, spinal cord, spleen, and stomach. Nine days from the onset of symptoms death resulted from asphyxiation due to extensive pulmonary hemorrhage probably caused by immun-mediated mechanisms. Circumstances suggest the victim probably ate inadequately cooked frog legs while hiking. Mesocercariae penetrated through the stomach wall and spread to the various organs both directly and via and circulatory system.