SIMULIT : un modèle de simulation pour l'analyse et la planification de l'activité hospitalière

Le modèle développé à l'Institut universitaire de médecine sociale et préventive de Lausanne utilise un programme informatique pour simuler les mouvements d'entrées et de sorties des hôpitaux de soins généraux. Cette simulation se fonde sur les données récoltées de routine dans les hôpitaux; elle tient notamment compte de certaines variations journalières et saisonnières, du nombre d'entrées, ainsi que du "Case-Mix" de l'hôpital, c'est-à-dire de la répartition des cas selon les groupes cliniques et l'âge des patients.

Intravenous streptomycin dosing regimen in a patient undergoing hemodialysis: Plasma level monitoring and pharmacokinetic simulation

Introduction: Streptomycin, as other aminoglycosides, exhibits concentration-dependent bacterial killing but has a narrow therapeutic window. It is primarily eliminated unchanged by the kidneys. Data and dosing information to achieve a safe regimen in patients with chronic renal failure undergoing hemodialysis (HD) are scarce. Although main adverse reactions are related to prolonged, elevated serum concentrations, literature recommendation is to administer streptomycin after each HD. Patients (or Materials) and Methods: We report the case of a patient with end-stage renal failure, undergoing HD, who was successfully treated with streptomycin for gentamicin-resistant Enterococcus faecalis bacteremia with prosthetic arteriovenous fistula infection. Streptomycin was administered intravenously 7.5 mg/kg, 3 hours before each dialysis (3 times a week) during 6 weeks in combination with amoxicillin. Streptomycin plasma levels were monitored with repeated blood sampling before, after, and between HD sessions. A 2-compartment model was used to reconstruct the concentration time profile over days on and off HD. Results: Streptomycin trough plasma-concentration was 2.8 mg/L. It peaked to 21.4 mg/L 30 minutes after intravenous administration, decreased to 18.2 mg/L immediately before HD, and dropped to 4.5 mg/L at the end of a 4-hour HD session. Plasma level increased again to 5.7 mg/L 2 hours after the end of HD and was 2.8 mg/L 48 hours later, before the next administration and HD. The pharmacokinetics of streptomycin was best described with a 2-compartment model. The computer simulation fitted fairly well to the observed concentrations during or between HD sessions. Redistribution between the 2 compartments after the end of HD reproduced the rebound of plasma concentrations after HD. No significant toxicity was observed during treatment. The outcome of the infection was favorable, and no sign of relapse was observed after a follow-up of 3 months. Conclusion: Streptomycin administration of 7.5 mg/kg 3 hours before HD sessions in a patient with end-stage renal failure resulted in an effective and safe dosing regimen. Monitoring plasma levels along with pharmacokinetic simulation document the suitability of this dosing scheme, which should replace current dosage recommendations for streptomycin in HD.

A pseudo-spectral method for the simulation of poro-elastic seismic wave propagation in 2D polar coordinates using domain decomposition

We present a novel numerical approach for the comprehensive, flexible, and accurate simulation of poro-elastic wave propagation in 2D polar coordinates. An important application of this method and its extensions will be the modeling of complex seismic wave phenomena in fluid-filled boreholes, which represents a major, and as of yet largely unresolved, computational problem in exploration geophysics. In view of this, we consider a numerical mesh, which can be arbitrarily heterogeneous, consisting of two or more concentric rings representing the fluid in the center and the surrounding porous medium. The spatial discretization is based on a Chebyshev expansion in the radial direction and a Fourier expansion in the azimuthal direction and a Runge-Kutta integration scheme for the time evolution. A domain decomposition method is used to match the fluid-solid boundary conditions based on the method of characteristics. This multi-domain approach allows for significant reductions of the number of grid points in the azimuthal direction for the inner grid domain and thus for corresponding increases of the time step and enhancements of computational efficiency. The viability and accuracy of the proposed method has been rigorously tested and verified through comparisons with analytical solutions as well as with the results obtained with a corresponding, previously published, and independently bench-marked solution for 2D Cartesian coordinates. Finally, the proposed numerical solution also satisfies the reciprocity theorem, which indicates that the inherent singularity associated with the origin of the polar coordinate system is adequately handled.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Association of different lipid measures for atherogenic lipid fractions and risk of coronary events in patients receiving combination antiretroviral therapy: the Swiss HIV Cohort Study

Background: Evidence for a better performance of different highly atherogenic versus traditional lipid parameters for coronary heart disease (CHD) risk prediction is conflicting. We investigated the association of the ratios of sma11 dense low density lipoprotein(LDL)/apoplipoprotein A, aolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol and CHD events in patients on combination antiretroviral therapy (cART).Methods: Case control study nested into the Swiss HIV Cohort Study: for each cART-treated patient with a first coronary event between April 1, 2000 and July 31, 2008 (case) we selected four control patients (1) that were without coronary events until the date of the event of the index case, (2) had a plasma sample within ±30 days of the sample date of the respective case, (3) received cART and (4) were then matched for age, gender and smoking status. Lipoproteins were measured by ultracentrifugation. Conditional logistic regression models were used to estimate the independent effects of different lipid ratios and the occurrence of coronary events.Results: In total, 98 cases (19 fatal myocardial infarctions [MI] and 79 non-fatal coronary events [53 definite MIs, 15 possible MIs and 11 coronary angioplasties or bypassesJ) were matched with 392 controls. Cases were more often injecting drug users, less likely to be virologically suppressed and more often on abacavir-containing regimens. In separa te multivariable models of total cholesterol, triglycerides, HDL-cholesterol, systolic blood pressure, abdominal obesity, diabetes and family history of CHD, small dense-LDL and apolipoprotein B were each statistically significantly associated with CHD events (for 1 mg/dl increase: odds ratio [OR] 1.05, 95% CI 1.00-1.11 and 1.15, 95% CI 1.01-1.31, respectively), but the ratiosof small dense-LDLlapolipoprotein A-I (OR 1.26, 95% CI 0.95-1.67), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and HDL-cholesterol! total cholesterol (OR 0.99 95% CI 0.98-1.00) were not. Following adjustment for HIV related and cART variables these associations were weakened in each model: apolipoprotein B (OR 1.27, 95% CI 1.00-1.30), sd-LDL (OR 1.04, 95% CI 0.99-1.20), small dense-LDLlapolipoprotein A-I (OR 1.17, 95% CI 0.87-1.58), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and total cholesterolJHDL- cholesterol (OR 0.99, 95% CI 0.99-1.00).Conclusions: In patients receiving cART, small dense-LDL and apolipoprotein B showed the strongest associations with CHD events in models controlling for traditional CHD risk factors including total cholesterol and triglycerides. Adding small dense LDLlapoplipoprotein A-l, apolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol ratios did not further improve models of lipid parameters and associations of increased risk for CHD events.

Evénements traumatiques et réponses de stress: le rôle de l'ocytocine et de l'attachement [Traumatic events and stress responses: the role of oxytocin and attachement].

Being repeatedly confronted to very difficult situations since childhood influences the way indivuals will later respond to even mildly stressful events. The hypothalamic-pituitary-adrenal axis (HPA) is a complex system implicated in regulating neuroendocrine responses to stress. Its activation produces among others the <stress hormonea, cortisol. However, the regulation of the physiological response to stress depends on psychological factors linked with the representations that individuals develop regarding their close relationships i.e. attachment. Furthermore, attachment representations seem to be associated with oxytocin, a hormone involved both in cortisol reduction and in positive social behaviours.

Genome-Wide Prediction Methods in Highly Diverse and Heterozygous Species: Proof-of-Concept through Simulation in Grapevine.

Nowadays, genome-wide association studies (GWAS) and genomic selection (GS) methods which use genome-wide marker data for phenotype prediction are of much potential interest in plant breeding. However, to our knowledge, no studies have been performed yet on the predictive ability of these methods for structured traits when using training populations with high levels of genetic diversity. Such an example of a highly heterozygous, perennial species is grapevine. The present study compares the accuracy of models based on GWAS or GS alone, or in combination, for predicting simple or complex traits, linked or not with population structure. In order to explore the relevance of these methods in this context, we performed simulations using approx 90,000 SNPs on a population of 3,000 individuals structured into three groups and corresponding to published diversity grapevine data. To estimate the parameters of the prediction models, we defined four training populations of 1,000 individuals, corresponding to these three groups and a core collection. Finally, to estimate the accuracy of the models, we also simulated four breeding populations of 200 individuals. Although prediction accuracy was low when breeding populations were too distant from the training populations, high accuracy levels were obtained using the sole core-collection as training population. The highest prediction accuracy was obtained (up to 0.9) using the combined GWAS-GS model. We thus recommend using the combined prediction model and a core-collection as training population for grapevine breeding or for other important economic crops with the same characteristics.

Tax simulation in the SHP

This paper describes a simulation package designed to estimate the annual income taxes paid by respondents of the Swiss Household Panel (SHP). In Switzerland, the 26 cantons have their own tax system. Additionally, tax levels vary between the over 2000 municipalities and over time. The simulation package takes account of this complexity by building on existing tables on tax levels which are provided by the Swiss Federal Tax Administration Office. Because these are limited to a few types of households and only 812 municipalities, they have to be extended to cover all households and municipalities. A further drawback of these tables is that they neglect several deductions. The tax simulation package fills this gap by taking additionally account of deductions for children, double-earner couples, third pillar and support for dependent persons according to cantonal legislation. The resulting variable on direct taxes not only serves to calculate household income net of taxes, but can also be a variable for analysis by its own account.

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.

BACKGROUND: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs). METHODS: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs. RESULTS: Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate. CONCLUSIONS: The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.

How many diagnosis fields are needed to capture safety events in administrative data? Findings and recommendations from the WHO ICD-11 Topic Advisory Group on Quality and Safety

OBJECTIVE: As part of the WHO ICD-11 development initiative, the Topic Advisory Group on Quality and Safety explores meta-features of morbidity data sets, such as the optimal number of secondary diagnosis fields. DESIGN: The Health Care Quality Indicators Project of the Organization for Economic Co-Operation and Development collected Patient Safety Indicator (PSI) information from administrative hospital data of 19-20 countries in 2009 and 2011. We investigated whether three countries that expanded their data systems to include more secondary diagnosis fields showed increased PSI rates compared with six countries that did not. Furthermore, administrative hospital data from six of these countries and two American states, California (2011) and Florida (2010), were analysed for distributions of coded patient safety events across diagnosis fields. RESULTS: Among the participating countries, increasing the number of diagnosis fields was not associated with any overall increase in PSI rates. However, high proportions of PSI-related diagnoses appeared beyond the sixth secondary diagnosis field. The distribution of three PSI-related ICD codes was similar in California and Florida: 89-90% of central venous catheter infections and 97-99% of retained foreign bodies and accidental punctures or lacerations were captured within 15 secondary diagnosis fields. CONCLUSIONS: Six to nine secondary diagnosis fields are inadequate for comparing complication rates using hospital administrative data; at least 15 (and perhaps more with ICD-11) are recommended to fully characterize clinical outcomes. Increasing the number of fields should improve the international and intra-national comparability of data for epidemiologic and health services research, utilization analyses and quality of care assessment.

Multiple plume events in the genesis of the peri-Caribbean Cretaceous oceanic plateau province

The oceanic crust fragments exposed in central America, in north-western South America, and in the Caribbean islands have been considered to represent accreted remnants of the Caribbean-Colombian Oceanic Plateau (CCOP). On the basis of trace element and Nd, Sr, and Pb isotopic compositions we infer that cumulate rocks, basalts, and diabases from coastal Ecuador have a different source than the basalts from the Dominican Republic. The latter suite includes the 86 Ma basalts of the Duarte Complex which are light rare earth element (REE) -enriched and display (relative to normal mid-ocean ridge basalts, NMORB) moderate enrichments in large ion lithophile elements, together with high Nb, Ta, Pb, and low Th contents. Moreover, they exhibit a rather restricted range of Nd and Pb isotopic ratios consistent with their derivation from an ocean island-type mantle source, the composition of which includes the HIMU (high U-238/Pb-204) component characteristic of the Galapagos hotspot. In contrast, the 123 Ma Ecuadorian oceanic rocks have flat REE patterns and (relative to NMORB) are depleted in Zr, Hf, Th, and U. Moreover, they show a wide range of Nd and Pb isotopic ratios intermediate between those of ocean island basalts and NMORB. It is unlikely, on geochemical grounds, that the plume source of the Ecuadorian fragments was similar to that of the Galapagos. In addition, because of the NNE motion of the Farallon plate during the Early Cretaceous, the Ecuadorian oceanic plateau fragments could not have been derived from the Galapagos hotspot but were likely formed at a ridge-centered or near-ridge hotspot somewhere in the SE Pacific.

RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies.

Direct simulation of interface dynamics: linking capillary pressure, interfacial area and surface energy

We perform direct numerical simulations of drainage by solving Navier- Stokes equations in the pore space and employing the Volume Of Fluid (VOF) method to track the evolution of the fluid-fluid interface. After demonstrating that the method is able to deal with large viscosity contrasts and to model the transition from stable flow to viscous fingering, we focus on the definition of macroscopic capillary pressure. When the fluids are at rest, the difference between inlet and outlet pressures and the difference between the intrinsic phase average pressure coincide with the capillary pressure. However, when the fluids are in motion these quantities are dominated by viscous forces. In this case, only a definition based on the variation of the interfacial energy provides an accurate measure of the macroscopic capillary pressure and allows separating the viscous from the capillary pressure components.