University of Udine

About: University of Udine is a education organization based out in Udine, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 6745 authors who have published 20530 publications receiving 669088 citations. The organization is also known as: Università degli Studi di Udine & Universita degli Studi di Udine.

Pharmacokinetic Considerations for Antimicrobial Therapy in Patients Receiving Renal Replacement Therapy

Abstract: Continuous renal replacement therapy (CRRT), particularly continuous venovenous haemofiltration (CVVH) and continuous venovenous haemodiafiltration (CVVHDF), are gaining increasing relevance in routine clinical management of intensive care unit patients. The application of CRRT, by leading to extracorporeal clearance (CLCRRT), may significantly alter the pharmacokinetic behaviour of some drugs. This may be of particular interest in critically ill patients presenting with life-threatening infections, since the risk of underdosing with antimicrobial agents during this procedure may lead to both therapeutic failure and the spread of breakthrough resistance. The intent of this review is to discuss the pharmacokinetic principles of CLCRRT of antimicrobial agents during the application of CVVH and CVVHDF and to summarise the most recent findings on this topic (from 1996 to December 2006) in order to understand the basis for optimal dosage adjustments of different antimicrobial agents. Removal of solutes from the blood through semi-permeable membranes during RRT may occur by means of two different physicochemical processes, namely, diffusion or convection. Whereas intermittent haemodialysis (IHD) is essentially a diffusive technique and CVVH is a convective technique, CVVHDF is a combination of both. As a general rule, the efficiency of drug removal by the different techniques is expected to be CVVHDF > CVVH > IHD, but indeed CLCRRT may vary greatly depending mainly on the peculiar physicochemical properties of each single compound and the CRRT device’s characteristics and operating conditions. Considering that RRT substitutes for renal function in clearing plasma, CLCRRT is expected to be clinically relevant for drugs with dominant renal clearance, especially when presenting a limited volume of distribution and poor plasma protein binding. Consistently, CLCRRT should be clinically relevant particularly for most hydrophilic antimicrobial agents (e.g. β-lactams, aminoglycosides, glycopeptides), whereas it should assume much lower relevance for lipophilic compounds (e.g. fluoroquinolones, oxazolidinones), which generally are nonrenally cleared. However, there are some notable exceptions: ceftriax-one and oxacillin, although hydrophilics, are characterised by primary biliary elimination; levofloxacin and ciprofloxacin, although lipophilics, are renally cleared. As far as CRRT characteristics are concerned, the extent of drug removal is expected to be directly proportional to the device’s surface area and to be dependent on the mode of replacement fluid administration (predilution or postdilution) and on the ultrafiltration and/or dialysate flow rates applied. Conversely, drug removal by means of CVVH or CVVHDF is unaffected by the drug size, considering that almost all antimicrobial agents have molecular weights significantly lower (<2000Da) than the haemofilter cut-off (30 000–50 000Da). Drugs that normally have high renal clearance and that exhibit high CLCRRT during CVVH or CVVHDF may need a significant dosage increase in comparison with renal failure or even IHD. Conversely, drugs that are normally nonrenally cleared and that exhibit very low CLCRRT during CVVH or CVVHDF may need no dosage modification in comparison with normal renal function. Bearing these principles in mind will almost certainly aid the management of antimicrobial therapy in critically ill patients undergoing CRRT, thus containing the risk of inappropriate exposure. However, some peculiar pathophys-iological conditions occurring in critical illness may significantly contribute to further alteration of the pharmacokinetics of antimicrobial agents during CRRT (i.e. hypoalbuminaemia, expansion of extracellular fluids or presence of residual renal function). Accordingly, therapeutic drug monitoring should be considered a very helpful tool for optimising drug exposure during CRRT.

Impacts of European drought events: insights from an international database of text-based reports

Abstract: Drought is a natural hazard that can cause a wide range of impacts affecting the environment, society, and the economy. Providing an impact assessment and reducing vulnerability to these impacts for regions beyond the local scale, spanning political and sectoral boundaries, requires systematic and detailed data regarding impacts. This study presents an assessment of the diversity of drought impacts across Europe based on the European Drought Impact report Inventory (EDII), a unique research database that has collected close to 5000 impact reports from 33 European countries. The reported drought impacts were classified into major impact categories, each of which had a number of subtypes. The distribution of these categories and types was then analyzed over time, by country, across Europe and for particular drought events. The results show that impacts on agriculture and public water supply dominate the collection of drought impact reports for most countries and for all major drought events since the 1970s, while the number and relative fractions of reported impacts in other sectors can vary regionally and from event to event. The analysis also shows that reported impacts have increased over time as more media and website information has become available and environmental awareness has increased. Even though the distribution of impact categories is relatively consistent across Europe, the details of the reports show some differences. They confirm severe impacts in southern regions (particularly on agriculture and public water supply) and sector-specific impacts in central and northern regions (e.g., on forestry or energy production). The protocol developed thus enabled a new and more comprehensive view on drought impacts across Europe. Related studies have already developed statistical techniques to evaluate the link between drought indices and the categorized impacts using EDII data. The EDII is a living database and is a promising source for further research on drought impacts, vulnerabilities, and risks across Europe. A key result is the extensive variety of impacts found across Europe and its documentation. This insight can therefore inform drought policy planning at national to international levels.