Emergency preparedness, resilience and response to a biological outbreak.

Major disease outbreaks continue to be a significant risk to public health, with pandemic influenza or an emerging infectious disease outbreak at the top of the UK National Risk Register. The risk of deliberate release of a biological agent is lower but remains possible and may only be recognised after casualties seek medical attention. In this context the emergency preparedness, resilience and response (EPRR) process protects the public from high consequence infectious diseases, other infectious disease outbreaks and biological agent release. The core elements of the EPRR response are recognition of an outbreak, isolation of patients, appropriate personal protective equipment for medical staff and actions to minimise further disease spread. The paper discusses how high-threat agents may be recognised by clinicians, the initial actions to be taken on presentation and how the public health system is notified and responds. It draws on the national pandemic influenza plans to describe the wider response to a major disease outbreak and discusses training requirements and the potential role of the military.

Cost-benefit analysis of central softening for production of drinking water.

Softening drinking water before distribution yields advantages with environmental impact, such as lower household products consumption, less scaling in piping and machines, and the avoidance of decentralized, domestic softeners. Central softening is under consideration in Flanders by the largest water supplier, VMW (Dutch acronym for "Flemish Company for Water Supply"), to deliver soft (15 degrees F) water to their customers. A case study is presented for a region with hard water (47 degrees F). The chosen technique is the pellet reactor, based on precipitation of CaCO(3) by NaOH addition. This softening operation has possibly large impact on the environment and the water consumption pattern. A cost-benefit analysis has been made to estimate the added value of central softening, by investigating the impact on the drinking water company, on their customers, on employment, on environment, on health, etc. The analysis for the region of study revealed benefits for customers which were higher than the costs for the drinking water company. However, pricing of drinking water remains an important problem. A sensitivity analysis of these results has also been made, to evaluate the impact of important hypothesis, and to be able to expand this study to other regions. The conclusions for this part show that softening is beneficial if water hardness is to be decreased by at least 5 degrees F.

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model.

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.

Cytokine removal with a large pore cellulose triacetate filter: an ex vivo study.

OBJECTIVE: To test the hypothesis that hemofiltration using a new large pore cellulose triacetate hemofilter can achieve effective ultrafiltration of cytokines. DESIGN: Ex-vivo study. SETTING: Laboratory of Intensive Care Unit in tertiary hospital. SUBJECTS: Six healthy volunteers. INTERVENTIONS: Blood from 6 volunteers was incubated for 4 hours with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore cellulose triacetate hemofilter (nominal cut-off point: 60 kilodaltons). Hemofiltration was conducted at 1 L/h or 6 L/h of ultrafiltrate (UF) flow at the start of extra-corporeal circulation, and after 2 and 4 hours. Samples were taken from the arterial, venous and UF sampling ports. MEASUREMENTS AND MAIN RESULTS: IL-Ibeta, IL-6, IL-8, IL-10, TNFalpha, and albumin were measured. Sieving coefficients (SC) above 0.6 were achieved for IL-Ibeta and IL-6 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 L/h. Sieving coefficients of all cytokines (except IL-10, p=0.22) were reduced when the ultrafiltration rate was increased from IL/h to 6 L/h (p<0.01), but the increase in ultrafiltration rate resulted in an overall increase in the clearance of all cytokines (p<0.001). The highest SC for albumin was 0.07 at 4 hours at 1 L/h, and fell to 0.01 at 6 L/h. The SCs for IL-8 fell at 4 hours (p<0.01), but the SCs for other cytokines did not change. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume hemofiltration (HVHF) using a new large pore cellulose triacetate filter achieved cytokine clearances greater than those reported with currently available hemo filters.

Dialysate flow distribution in hollow fiber hemodialyzers with different dialysate pathway configurations.

UNLABELLED: The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, since this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different dialysate compartment designs on dialysate flow distribution and urea clearances. Eighteen hollow fiber 1.3 m2 hemodialyzers were studied, 6 each of 3 designs: Type A--standard fiber bundle (PAN 65DX Asahi Medical, Tokyo, Japan); Type B--spacing filaments external to the fibers (PAN 65SF Asahi Medical, Tokyo, Japan); Type C--fibers waved to give Moiré structure (FB130 Nissho-Nipro, Osaka, Japan). IN VITRO STUDIES: 3 dialyzers of each type were studied following dye injection into the dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer were undertaken, using a new generation helical CT scanner (X-Press/HS1 Toshiba Corporation, Tokyo, Japan). In vivo studies: 3 dialyzers of each type were studied, in randomized sequence, in 3 different patients under standardized dialysis conditions. Blood- and dialysate-side urea clearances were measured at 30 and 150 minutes of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (Type C) and least homogeneous in the standard dialyzer (Type A). Space yarns (Type B) gave an intermediate dialysate flow distribution. Significantly increased urea clearances (p<0.001) were seen with Types B and C, compared to the standard dialyzer. Type C (Moiré) had the highest clearances although these were not significantly greater than Type B (space yarns). In conclusion, more homogeneous dialysate flow distribution and improved small solute clearances can be achieved by use of spacing yarns or waved (Moiré structure) patterns of fiber packing in the dialyzer. These effects are achieved probably as a result of reduced dialysate channeling resulting in a lower degree of mismatch between blood and dialysate flows. The new radiological technique using the helical CT scanner allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.

Cellulose triacetate: another membrane for continuous renal replacement therapy.

The evolution of technology and biomaterials has permitted a parallel development of renal replacement therapies in the acute, critically ill patient. From the original continuous artero-venous hemofiltration method new techniques such as continuous veno-venous hemofiltration, hemodiafiltration and high-flux dialysis have been developed and are clinically used. Similar progress has been made with artificial membranes. We investigated the possibility of using a modified cellulosic membrane for continuous therapies, assessing the hydraulic characteristics and clearance performances of high-flux cellulose triacetate hemodiafilter (0.7 m2) in vitro and in vivo. The flowdynamic characteristics of the filter suggest its optimal use in veno-venous pump-drive techniques. Efficiency was excellent, with urea daily clearances as high as 50 liters or more. The high permeability and porosity of the membrane also increased the clearances of larger solutes such as creatinine and inulin. No side effects occurred during treatment and we conclude that cellulose triacetate may be considered a good alternative to synthetic membranes in continuous renal replacement therapies.