Identifying barriers in telesurgery by studying current team practices in robot-assisted surgery

This paper investigates challenges in current practices in robot-assisted surgery. In addition, by using the method of proxy technology assessment, we provide insights into the current barriers to wider application of robot-assisted telesurgery, where the surgeon and console are physically remote from the patient and operating team. Research in this field has focused on the financial and technological constraints that limit such application; less has been done to clarify the complex dynamics of an operating team that traditionally works in close symbiosis. Results suggest that there are implications for working practices in transitioning from traditional robot-assisted surgery to remote robotic surgery that need to be addressed, such as possible communication problems which might have a negative impact on patient outcomes

A semiphysiological population pharmacokinetic model of agomelatine and its metabolites in Chinese healthy volunteers

Aims: Agomelatine is an antidepressant for major depressive disorders. It undergoes extensive first-pass hepatic metabolism and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects. Methods: Plasma concentration-time data of agomelatine and its metabolites were collected from a 4-period, cross-over bioequivalence study, in which 44 healthy subjects received 25 mg agomelatine tablets orally. Nonlinear mixed effects modelling was used to characterize the pharmacokinetics and variability of agomelatine and its metabolites. Deterministic simulations were carried out to investigate the influence of pathological changes due to liver disease on agomelatine pharmacokinetics. Results: A semiphysiological pharmacokinetic model with parallel first-order absorption and a well-stirred liver compartment adequately described the data. The estimated IIV and interoccasion variability of the intrinsic clearance of agomelatine were 130.8% and 28.5%, respectively. The IIV of the intrinsic clearance turned out to be the main cause of the variability of area under the curve-based agomelatine exposure. Simulations demonstrated that a reduction in intrinsic clearance or liver blood flow, and an increase in free drug fraction had a rather modest influence on agomelatine exposures (range: -50 to 200%). Portosystemic shunting, however, substantially elevated agomelatine exposure by 12.6-109.1-fold. Conclusions: A semiphysiological pharmacokinetic model incorporating first-pass hepatic extraction was developed for agomelatine and its main metabolites. The portosystemic shunting associated with liver disease might lead to significant alterations of agomelatine pharmacokinetics, and lead to substantially increased exposure

Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer

Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 mu g PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTX-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D= 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer

Inactivation of Salmonella , Listeria monocytogenes and Escherichia coli O157:H7 inoculated on coriander by freeze-drying and supercritical CO 2 drying

Coriander, either fresh or inoculated with three strains of Escherichia coli O157:H7, Salmonella or Listeria monocytogenes, was treated with supercritical CO2 (scCO(2), with and without drying) or freeze-dried. After drying in scCO(2) for 150 min at 80 bar and 35 degrees C, the aerobic plate count, yeasts and molds, and the Enterobacteriaceae were reduced by 2.80, 5.03, and 4.61 log CFU/g, respectively. The total count of mesophilic aerobic spores was not significantly reduced by the treatment. Freeze-drying induced lower reductions with 1.23, 0.87, and 0.97 log CFU/g, respectively. After treatment at 100 bar and 40 degrees C without drying, inoculated strains of E. coli O157:H7, Salmonella, and L. monocytogenes were inactivated by > 7.37, > 4.73 and 4.99 log CFU/g, respectively. After drying in scCO 2 for 150 min at 80 bar and 35 degrees C, the strains were reduced by > 5.18 log CFU/g. Freeze-drying resulted in lower reduction with maximum 1.53, 2.03, and 0.71 log CFU/g, respectively. This study indicated that scCO(2) can be used for drying while offering a good inactivation of E. coli O157:H7, Salmonella, and L. monocytogenes as well as most of the bacteria in the vegetative form naturally occurring on coriander. Industrial relevance: Although dried foods are considered microbiological stable foods and show adverse conditions to microbial growth, they may still host pathogenic microorganisms, which may proliferate upon sufficient rehydration. Highly contaminated commodities such as herbs and spices can pose a threat to consumer health if not processed carefully. There is therefore a need to develop or improve drying techniques which can provide dried foods while reducing the initial contamination to acceptable levels in a single process. CO2 is a cheap, accessible solvent, with a low critical point (31 degrees C, 73.8 bar). Moreover, in the supercritical region, CO, exhibits potent microbicidal properties. Therefore, supercritical CO2 drying could be a valuable alternative nonthermal technique for conventional drying methods, such as air-drying or freeze-drying, when medium to high value-added food products with high initial contamination are involved