Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration

Background. The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. Methods. Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo) and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance. Results. A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2±4.6 (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained. Conclusions. Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo+fu UFR/CLn with the dose considered appropriate in the absence of renal impairmen

Precautionary Measures for Credit Risk Management in Jump Models

Sustaining efficiency and stability by properly controlling the equity to asset ratio is one of the most important and difficult challenges in bank management. Due to unexpected and abrupt decline of asset values, a bank must closely monitor its net worth as well as market conditions, and one of its important concerns is when to raise more capital so as not to violate capital adequacy requirements. In this paper, we model the tradeoff between avoiding costs of delay and premature capital raising, and solve the corresponding optimal stopping problem. In order to model defaults in a bank's loan/credit business portfolios, we represent its net worth by Levy processes, and solve explicitly for the double exponential jump diffusion process and for a general spectrally negative Levy process.Comment: 31 pages, 4 figure

Optimal Dividend Payments for the Piecewise-Deterministic Poisson Risk Model

This paper considers the optimal dividend payment problem in piecewise-deterministic compound Poisson risk models. The objective is to maximize the expected discounted dividend payout up to the time of ruin. We provide a comparative study in this general framework of both restricted and unrestricted payment schemes, which were only previously treated separately in certain special cases of risk models in the literature. In the case of restricted payment scheme, the value function is shown to be a classical solution of the corresponding HJB equation, which in turn leads to an optimal restricted payment policy known as the threshold strategy. In the case of unrestricted payment scheme, by solving the associated integro-differential quasi-variational inequality, we obtain the value function as well as an optimal unrestricted dividend payment scheme known as the barrier strategy. When claim sizes are exponentially distributed, we provide easily verifiable conditions under which the threshold and barrier strategies are optimal restricted and unrestricted dividend payment policies, respectively. The main results are illustrated with several examples, including a new example concerning regressive growth rates.Comment: Key Words: Piecewise-deterministic compound Poisson model, optimal stochastic control, HJB equation, quasi-variational inequality, threshold strategy, barrier strateg

Creative music therapy for long-term neurodevelopment in extremely preterm infants: Results of a feasibility trial

AIM: We tested the feasibility of a future randomised clinical trial (RCT) in which Creative Music Therapy (CMT), a family-integrating individualised approach in neonatal care, could improve neurodevelopment in extremely preterm infants (EPTs). METHODS: In this feasibility trial, 12 EPTs received CMT, while the remaining 19 received standard neonatal care. Socio-demographic data and perinatal complications were compared between groups as risk factors. Bayley Scales of Infant and Toddler Development at 2-year follow-up (FU2) and KABC-II-Kaufman Assessment Battery for Children at 5-year follow-up (FU5) were analysed using the Mann-Whitney U-tests. RESULTS: Twenty-seven (87.1%) and 18 (58.1%) EPTs attended the FU2 and FU5 examination, respectively. The rate of neurodevelopmental risk factors at birth of the two groups was quite similar. While there was no difference in the FU2 outcomes between groups, there were higher values in the CMT group's Fluid-Crystallised Index of the KABC-II. CONCLUSION: Our results indicate neither a beneficial nor a detrimental effect of CMT on neurodevelopment at 2 years but a trend of improved cognitive outcomes at 5 years more similar to cognitive scores of term-born infants than of standard treatment EPTs. The findings favour an RCT but must be interpreted cautiously due to the reduced sample size and non-randomised design

Small Is Beautiful: Why Profundaplasty Should Not Be Forgotten

Background: Surgical profundaplasty (SP)is used mainly as an adjunct to endovascular management of peripheral vascular disease (PAD) today. Results from earlier series of profundaplasty alone have been controversial, especially regarding its hemodynamic effect. The question is: Can profundaplasty alone still be useful? Our aim was to evaluate its role in the modern management of vascular patients. Methods: This was a retrospective outcome study. A consecutive series of 97 patients (106 legs) from January 2000 through December 2003 were included. In 55 (52%) legs, the superficial femoral artery was occluded. These patients were included in the current analysis. Of these patients 14 (25%) were female. Mean age was 71 ((11) years. Nineteen (35%) were diabetic. The indication for operation was claudication in 29 (53%), critical leg ischemia (CLI) in 26 (47%), either with rest pain in 17 (31%), or ulcer/gangrene in 9 (16%). Endarterectomy with patch angioplasty with bovine pericardium was performed in all cases. Mean follow-up was 33(14 months. Mean preoperative ankle brachial index (ABI) was 0.6. Sustained clinical efficacy was defined as upward shift of 1 or greater on the Rutherford scale without repeat target limb revascularization (TLR) or amputation. Mortality, morbidity, need for TLR, or amputation were separate endpoints. Results: Postoperatively, ABI was significantly improved (mean=0.7), in 24 (44%) by more than 0.15. At three years, cumulative clinical success rate was 80%. Overall, patients with claudication had a better outcome than those with CLI (p=0.04). Two (4%) major amputations and 2 (4%) minor ones were performed, all in patients with CLI. None of the 9 (16%) ulcers healed. Conclusion: Profundaplasty is still a valuable option for patients with femoral PAD and claudication without tissue loss. It is a straightforward procedure that combines good efficacy with low complication rates. Further endovascular treatment may be facilitated. It is not useful for patients with the combination of critical ischemia and tissue los

Digitalisierungsfortschritt föderaler Einheiten : ein Vergleich der Ausgestaltungen kantonaler ePlattformen in der Schweiz

Die Digitalisierung hält nicht nur in Wirtschaft und Gesellschaft Einzug, sondern auch im öffentlichen Sektor finden Digitalisierungsprozesse statt. Electronic Government (eGovernment) bezeichnet die Gesamtheit der elektronischen Dienstleistungen öffentlicher Verwaltungen. Mittels eGovernment sollen Prozesse sowohl optimiert als auch durchgeführt werden. In föderalen Staaten wie der Schweiz unterliegt die Implementierung technischer Systeme dem Subsidiaritätsprinzip. Es stellt sich deshalb die Frage, ob und worin sich der Digitalisierungsfortschritt von Kantonen unterscheidet. Ziel der Studie ist es, eine systematische Übersicht über Charakteristika verschiedener kantonaler ePlattform-Lösungen in der Schweiz zu erstellen. Gleichzeitig wird die Ausgestaltung von eGovernment-Lösungen mit Hilfe verschiedener Faktoren der technischen Umsetzung beurteilt. Mittels Dokumentenanalysen sowie einer Online-Befragung unter eGovernment-Verantwortlichen wurden Umfang und Ausgestaltung sämtlicher 26 kantonalen ePlattformen untersucht. Aus dem Modell zu Übernahmekategorien wurden Faktoren zur Ausgestaltung der technischen Umsetzung von eGovernment-Lösungen abgeleitet und auf den öffentlichen Sektor angewendet, um die eGovernment-Reife anhand der Ausprägungen der Kantone abzubilden. Das Modell der Übernahmekategorien unterteilt Systemmitglieder auf Basis ihrer Innovationsbereitschaft in fünf unterschiedliche Kategorien: Innovatoren, Frühe Übernehmer, Frühe Mehrheit, Späte Mehrheit und Nachzügler. Die Ergebnisse offenbaren einen heterogenen Innovationsgrad der Ausgestaltungen kantonaler ePlattformen. So entsprechen nur 4% der Kantone der Übernahmekategorie Innovatoren, wohingegen sich 23% der Kantone der Kategorie Nachzügler zuordnen lassen. Die Ergebnisse zur Beschaffenheit der Übernahmekategorien erlauben Schlussfolgerungen betreffend des Innovationsgrads verschiedener ePlattformen im schweizerischen Vergleich. Dadurch können die Ergebnisse dazu beitragen, dass sich die als Nachzügler identifizierten Kantone an den ePlattform Lösungen der Innovatoren als Vorbilder orientieren

Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery

Objective : Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. Methods and Results : Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups.Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. Conclusions : eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefi

Flow Cytometric microsphere-based immunoassay as a novel non-radiometric method for the detection of glutamic acid decarboxylase autoantibodies in type 1 Diabetes Mellitus

The first measurable sign of arising autoimmunity in Type 1 Diabetes Mellitus is the detection of autoantibodies against beta-cell antigens, such as glutamic acid decarboxylase (GAD65). GAD65 autoantibodies (GADA) are usually measured by Radioligand Binding Assay (RBA). The aim of this work was to develop protocols of Flow Cytometric microsphere-based immunoassays (FloCMIA) which involved glutamic acid decarboxylase fused to thioredoxin (TrxGAD65) adsorbed on polystyrene microspheres. Detection of bound GADA was accomplished by the use of anti-human IgG-Alexa Fluor 488 (Protocol A), anti-human IgG-biotin and streptavidindichlorotriazinyl aminofluorescein (DTAF) (Protocol B) or TrxGAD65-biotin and streptavidin- DTAF (Protocol C). Serum samples obtained from 46 patients assayed for routine autoantibodies at Servicios Tecnológicos de Alto Nivel (STAN-CONICET) were analyzed by RBA, ELISA and three alternative FloCMIA designs. Protocol C exhibited the highest specificity (97.8%) and sensitivity (97.4%) and a wide dynamic range (1.00-134.40 SDs). Samples obtained from 40 new-onset diabetic patients were also analyzed to further evaluate the performance of protocol C. The latter protocol showed a sensitivity of 58.6% and a prevalence of 47.5%. Two patients resulted positive only by FloCMIA protocol C and its SDs were higher than RBA and ELISA, showing a significantly wide dynamic range. In conclusion, FloCMIA proved to be highly sensitive and specific, requiring a low sample volume; it is environmentally adequate, innovative and it represents a cost-effective alternative to traditional GADA determination by RBA and/or ELISA; making it applicable to most medium-complexity laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Ureta, Daniela Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentin