Clinical Study Comparison of a Bayesian Network with a Logistic Regression Model to Forecast IgA Nephropathy

Models are increasingly used in clinical practice to improve the accuracy of diagnosis. The aim of our work was to compare a Bayesian network to logistic regression to forecast IgA nephropathy (IgAN) from simple clinical and biological criteria. Retrospectively, we pooled the results of all biopsies (n = 155) performed by nephrologists in a specialist clinical facility between 2002 and 2009. Two groups were constituted at random. The first subgroup was used to determine the parameters of the models adjusted to data by logistic regression or Bayesian network, and the second was used to compare the performances of the models using receiver operating characteristics (ROC) curves. IgAN was found (on pathology) in 44 patients. Areas under the ROC curves provided by both methods were highly significant but not different from each other. Based on the highest Youden indices, sensitivity reached (100% versus 67%) and specificity (73% versus 95%) using the Bayesian network and logistic regression, respectively. A Bayesian network is at least as efficient as logistic regression to estimate the probability of a patient suffering IgAN, using simple clinical and biological data obtained during consultation

Combined effect of renal function and serum potassium level in sudden cardiac death in aging hypertensive subjects

In patients with chronic kidney disease, serum potassium level is a factor influencing sudden cardiac death (SCD). The aim of our analysis was to study the combined effect of serum potassium level and renal function on the onset of SCD in elderly hypertensive subjects. Data from the 3620 hypertensive patients aged over 70 years were extracted from three randomized clinical trials included in the INDANA database. During a mean follow up of 4.5 years, 81 patients (2.24%) died from SCD. Mean serum potassium levels and prevalence of chronic kidney disease were not different in patients who died from SCD. In addition to serum potassium and creatinine levels, 14 clinical and biological variables linked to cardiovascular diseases recorded at baseline were analyzed using a Bayesian network. The area under the receiver operating characteristic curve of the Bayesian model reached 0.91. Bayesian inference was used to simulate the combined effects of serum potassium and creatinine levels on SCD. Our analysis, using simulated data from Bayesian model, showed that the estimated probabilities of SCD was significantly increased in case of hyperkalemia (>5.0 mmol/l) and in case of hypokalemia (<3.5 mmol/l) and in case of chronic kidney disease. Combined effects of serum potassium level and renal function revealed that chronic kidney disease increased the probability of SCD whatever the serum potassium level. Our results using a Bayesian model confirm the deleterious effects of hypokalemia, hyperkalemia and chronic kidney disease on SCD in elderly hypertensive patients.status: publishe

A novel method for calculating the energy barriers for carbon diffusion in ferrite under heterogeneous stress

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Aminoglycoside Nephrotoxicity: Modeling, Simulation, and Control

The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the least-squares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r(2) = 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs

Analysis of risk factors of hip fracture with causal Bayesian networks

International audienceWe explore a practical approach to learn a plausible causal Bayesian network from a combination of non-experimental data and qualitative assumptions that are deemed likely by health experts. The method is based on the incorporation of prior expert knowledge in the form of partial pairwise ordering constraints between variables into a recent constraint-based Bayesian network structure learning algorithm. The learning process ends up with a partially oriented graph. The remaining undirected edges are then oriented according to the expert understanding. We show that the causal graph not only provides a statistical profile of the population under study but also offers a simple guideline principle to identify accessible sets of confounding variables for each causal relation under interest. To illustrate the potential of the proposed approach, we estimate the strength of the causal effect of psychotropic drugs, gait speed, body mass index and bone mineral density on the risk of hip fracture from a prospective cohort study EPIDOS sample, which included more than 7500 elderly osteoporotic women followed-up during 4 years. Our findings suggest that an intervention programme aimed at preventing physical deterioration and maintaining bone mass density should tend to reduce the risk of hip fracture among elderly

Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen

International audienceObjectives: To investigate the population pharmacokinetics of teicoplanin in patients treated by the subcutaneous (sc) and/or intravenous (iv) route.Patients and methods: Non-linear mixed-effects modelling described teicoplanin concentrations from 98 patients with infection caused by Gram-positive cocci. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of various dosage regimens.Results: Teicoplanin concentrations were best described by a two-compartment model with clearance predicted by estimated glomerular filtration rate. Estimated absorption rate constant (between-subject variability) was 0.039 h-1 (77%), clearance was 0.305 L/h (28%), central volume was 10.3 L (49%), inter-compartmental clearance was 4.42 L/h (66%) and peripheral volume was 97.4 L (51%). The sc route was associated with lower initial Cmin and AUC (day 3: loading phase) compared with the iv route. This difference appeared to vanish after 14 days, with comparable simulated PTAs based on the Cmin and AUC for all tested dosages (400, 600, 800 and 1000 mg every 12 h). However, a loading dose regimen with five administrations of either 400 or 600 mg was not sufficient to achieve the target Cmin (≥15 mg/L) for both routes. Also, PTAs for higher MIC (≥1.0 mg/L) were poor with all regimens for both routes.Conclusions: This is the first study examining the pharmacokinetic/pharmacodynamic implications of using the sc route for teicoplanin. Subcutaneous administration is associated with lower Cmin and AUC values after the loading phase compared with iv administration. Therefore, iv administration should be preferred in the first few days of therapy. This study also shows that loading doses of teicoplanin higher than currently recommended should be used to improve PTA

Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D-tested population in France: a population-based descriptive cohort study

International audienceOBJECTIVE: Chronic vitamin D deficiency has been associated in some patients with diffuse musculoskeletal pain. These unspecific symptoms may partly explain why vitamin D deficiency is often diagnosed late. Our aim was to analyse health-care claims after vitamin D supplementation in patients likely to have vitamin D deficiency. DESIGN: Ambulatory health-care claims were compared before and after a vitamin D supplementation prescribed following a 25-hydroxyvitamin D assay. SETTING: Health Insurance Fund (FHIF) database of the Rhône-Alpes area, France. SUBJECTS: Among patients reimbursed for a 25-hydroxyvitamin D assay between 1 December 2008 and 31 January 2009, those supplemented with vitamin D after the assay were matched on the date of assay to patients who did not receive vitamin D. RESULTS: Among the 3023 patients who had a 25-hydroxyvitamin D assay, 935 were consequently supplemented and matched to 935 patients not supplemented. Their median age was 50\textperiodcentered0 and 49\textperiodcentered5 years, respectively. Patients supplemented decreased their muscle relaxant consumption whereas no change was observed in the reference group, the difference between the two groups was significant (P=0\textperiodcentered03). Second and third Pain Relief Ladder prescriptions decreased in both groups but not significantly differently between groups (P=0\textperiodcentered58). There was a decrease in prescriptions of biological examination in both groups with no significant difference. CONCLUSIONS: Besides a decrease in muscle relaxant prescriptions in the supplemented group, it was difficult to assess the impact of vitamin D supplementation in patients likely to have vitamin D deficiency. Prospective cohort studies and randomized trials are needed to assess the efficiency of screening and supplementing vitamin D deficiency