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OBJECTIVES:Paediatric patients receive less procedural sedation and analgesia (PSA) in the emergency department compared with adults, especially in countries where emergency medicine is at an early stage of development. The objectives of this study were to evaluate the adverse events and efficacy of paediatric PSA in a country with a recent establishment of emergency medicine and to describe which factors aided implementation.METHODS:This is a prospective, multicentre, observational study of paediatric patients undergoing PSA by the first trained emergency physicians (EPs) in The Netherlands. A standardized data collection form was used at all participating hospitals to collect data on adverse events, amnesia, pain scores, and procedure completion. A survey was used to interpret which factors had aided PSA implementation.RESULTS:We recorded 351 paediatric PSA. The mean age was 9.5 years (95% confidence interval: 9.1-10.0). Esketamine was most frequently used (42.4%), followed by propofol (34.7%). The adverse event rate was low (3.0%). Amnesia was present in 86.8%. The median pain score was 2 (out of 10) for patients without amnesia. Procedures were successfully completed in 93.9% of the cases.CONCLUSION:Paediatric PSA provided by the first EPs in The Netherlands showed appropriate levels of sedation and analgesia with a high rate of procedure completion and a low rate of adverse events. Our paper suggests that EPs provided with a proper infrastructure of mentorship, training and guidelines can implement effective paediatric PSA.

Background Several efforts have been made to assure and to improve the quality of procedural sedation and analgesia (PSA) performed by emergency physicians (EPs) in The Netherlands. This study investigated the current PSA practice and competences of EPs in both adult and paediatric patients. In particular, if residency and current training, awareness of guidelines is sufficient for registered EPs to adequately perform PSA and if the availability of both adult and paediatric PSA in the ED is adequate. Methods A cross-sectional nationwide survey was performed amongst Dutch EPs (n = 463) in June 2016. We collected data on background, training, practice, and competencies of both adult and paediatric PSA. We investigated guideline adherence, reasons for not performing PSA, and desired improvements. Results The respondents (n = 191) represented 84.6% hospitals with EPs and 41.3% of all EPs in The Netherlands. Nearly all EPs (97.8%) performed PSA in adult patients compared to only 59.1% who performed PSA in paediatric patients (p

Objective: To describe our experience performing ED procedural sedation in a country where emergency medicine (EM) is a relatively new specialty. Methods: This is a prospective observational study of adult patients undergoing procedural sedation by emergency physicians (EPs) or EM residents in eight hospitals in the Netherlands. Data were collected on a standardised form, including patient characteristics, sedative and analgesic used, procedural success, adverse events (classified according to World SIVA) and rescue interventions. Results: 1711 adult cases were included from 2006 to 2013. Propofol, midazolam and esketamine (S+ enantiomer of ketamine) were the most used sedatives (63%, 29% and 8%). We had adverse event data on all patients. The overall adverse event rate was 11%, mostly hypoxia or apnoea. There was no difference in adverse event rate between EPs and EM residents. However, there was a significantly higher success rate of the procedure when EPs did the procedural sedation (92% vs 84%). No moderate (unplanned hospital admission or escalation of care) or sentinel SIVA outcomes occurred ( pulmonary aspiration syndrome, death or permanent neurological deficit). Conclusion: Adverse events during procedural sedation occurred in 11% of patients. There were no moderate or sentinel outcomes. All events could be managed by the sedating physician. In a country where EM is a relatively new specialty, procedural sedation appears to be safe when performed by EPs or trained EM residents and has comparable adverse event rates to international studies.

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The solid-state fermentation (SSF) method described enabled accurate determination of variables related to biological activity. Growth, respiratory activity and production of carboxymethyl-cellulose-hydrolysing enzyme (CMC-ase) activity by Trichoderma reesei QM9414 on wheat bran was used as a model SSF. The standard deviation (s) of measured substrate weight loss and glucosamine content, and the overall standard deviation of oxygen consumption rate (OCR) and carbon-dioxide production rate (CPR) after 72 h of fermentation were less than 7% of the mean measured values. A statistical method to estimate the standard deviation of time-dependent data is presented. A closed carbon balance could be set up with the results of the measurements of CPR, elemental composition and chemical composition, indicating the reliability of the methods used. Measurements of CMC-ase activity were less accurate due to interaction between substrate and product. The measurement of the ATP level was also less accurate.

The theoretical mathematical models described in this paper are used to evaluate the effects of fungal biomass inactivation kinetics on a non- isothermal tray solid-state fermentation (SSF). The inactivation kinetics, derived from previously reported experiments done under isothermal conditions and using glucosamine content to represent the amount of biomass, are described in different ways leading to four models. The model predictions show only significant effects of inactivation kinetics on temperature and biomass patterns in the tray SSF after long fermentation periods. The models in which inactivation is triggered by low specific growth rates can predict restricted biomass evolution in combination with a fast temperature increase followed by a slower temperature decrease. Such inactivation might occur when substrate is limiting or products are formed in toxic concentrations. Temperature is predicted to be the key parameter. Oxygen concentration is predicted to become limiting only at high heat conduction and low oxygen diffusion rates. Desiccation of the substrate is predicted not to occur.

In this paper, correlations between temperature and kinetics of Trichoderma reesei QM9414 growing on wheat bran are described in terms of glucosamine production, oxygen consumption, and carbon dioxide production. Maximum growth temperature (T(max)) being approximately 314 K, is estimated by measuring the radial growth rate on wheat bran. The value is used in the description of the influence of temperature on the maximum specific growth rate (μ(max)) and maximum glucosamine (G(max)) level. Both correlations are described with a Ratkowsky-type equation. The highest value of μ(max) and G(max) are found at approximately 307 K and were 0.154 h-1 and 8.7 mg glucosamine g-1 initial dry matter, respectively. A Gaussian curve is used to describe the influence of temperature on yield factor which varies with a factor of 2 between 293 K and T(max). The maintenance coefficient is determined to be temperature independent. The observed decline in specific activity, measurable below and above T(max) reflects the sensitivity of the fungus to elevated temperatures. The decline rate increases exponentially above T(max).

A solid-state fermentation system, using polyurethane foam as an inert carrier, was used for the production of nuclease P1 by Penicillium citrinum. Optimization of nuclease P1 production was carried out using a synthetic liquid medium. After a two-step medium optimization using a fractional factorial experimental design, nuclease P1 productivity and specific activity are greatly increased. Nuclease P1 productivity and specific activity are ninefold and fourfold higher, respectively, than in solid-state fermentation of wheat bran and 500-fold and 20-fold higher, respectively, than in submerged fermentation. Additional advantages of the solid-state fermentation process using inert carrier are discussed. A solid-state fermentation system, using polyurethane foam as an inert carrier, was used for the production of nuclease P1 by Penicillium citrinum. Optimization of nuclease P1 production was carried out using a synthetic liquid medium. After a two-step medium optimization using a fractional factorial experimental design, nuclease P1 productivity and specific activity are greatly increased. Nuclease P1 productivity and specific activity are ninefold and fourfold higher, respectively, than in solid-state fermentation of wheat bran and 500-fold and 20-fold higher, respectively, than in submerged fermentation. Additional advantages of the solid-state fermentation process using inert carrier are discussed.

A description is given of the solid-state fermentation of wheat bran by Trichoderma reesei QM9414 at constant temperature and relative humidity. Glucosamine, the oxygen consumption rate (OCR), the carbon dioxide production rate (CPR), changes in wheat bran composition and the production of four enzymes were measured during 125 h of fermentation. A C balance was set up between CO2 production, based on CPR measurements, CO2 production as expected on the basis of substrate composition changes and substrate elemental composition in combination with dry-matter weight loss. Glucosamine was used as the measure of biomass. The results indicate that the glucosamine content of fungi in liquid culture cannot be used to estimate the biomass content in solid-state fermentations. Using glucosamine, correlations between fungal growth and respiration kinetics could only partly be described with the linear-growth model of Pirt. A decline in OCR and CPR started the moment the glucosamine level was 50% of its maximum value. After the glucosamine level had reached its maximum OCR and CPR continued to decline. The activities of xylanase and protease are linearly related to the glucosamine level. No clear correlations between glucosamine and carboxylmethylcellulose-hydrolysing enzyme activity and amylase activity were found.

A fuzzy model was developed to predict the glucosinolate content of rapeseed meal during solid-state fermentation. Process variables such as temperature, relative humidity, fermentation time and the resulting glucosinolate content of the meal were considered. The glucosinolate content calculated by the fuzzy model corresponded with the experimental results obtained by solid-state fermentation. A fuzzy model was developed to predict the glucosinolate content of rapeseed meal during solid-state fermentation. Process variables such as temperature, relative humidity, fermentation time and the resulting glucosinolate content of the meal were considered. The glucosinolate content calculated by the fuzzy model corresponded with the experimental results obtained by solid-state fermentation.

Two fungal strains, Aspergillus clavatus II-9 and Fusarium oxysporum @ 149, proved to be capable of degrading sinigrin and sinalbin. During the degradation of sinigrin by whole cells of the Aspergillus strain, allylcyanide accumulated in the liquid incubation mixture. After a maximum concentration had been reached, the concentration of allylcyanide decreased as a result of its instability in the medium used. Incubation of cell free extracts with sinigrin resulted in accumulation of glucose and allylisothiocyanate, suggesting that myrosinase is involved. Experiments with intact cells and cell-free extracts indicate the formation of an as yet unknown intermediate. When sinigrin was degraded by the Aspergillus strain in mustard seed meal under solid-state fermentation (SSF) conditions, no accumulation of allylcyanide or allylisothiocyanate was measured. Degradation of sinigrin by F. oxyspornm @ 149 did not result in accumulation of intermediates, neither in liquid incubation mixtures nor in mustard seed meal under SSF conditions. Sinigrin was not degraded during incubation with cell-free extracts of F. oxysporum @ 149. Degradation of sinalbin by A. clavatus and F. oxysporum was measured during fermentation of yellow mustard seed meal under SSF conditions. Both fungi are useful for laboratory-scale SSF of mustard seed meal, thus opening new perspectives for a cost effective detoxification process for raw feed materials. Chemicals/CAS: sinigrin, 3952-98-5