[Health Care Insurance in France: its impact on income distribution between age and social groups]. / Redistribution des revenus opérée par l'assurance maladie entre groupes d'âge et groupes sociaux.

Our study, based on microsimulation models, evaluates the redistributive impact of health care insurance in France on income distribution between age and social groups. This work sheds light on the debate concerning the respective role of the public health care insurance (PHI) and the private supplemental health care insurance (SHI) in France. The analysis points out that the PHI enables the lowest-income households and the pensioners a better access to health care than they would have had under a complete private SHI. Due to the progressivity of taxes, low-income households contribute less to the PHI and get higher benefits because of a weaker health. Pensioners have low contributions to public health care finance but the highest health care expenditures.

Failure of traditional trough levels to predict tacrolimus concentrations.

The objective of this study was to estimate tacrolimus population parameter values and to evaluate the ability of the maximum a posteriori probability (MAP) Bayesian fitting procedure to predict tacrolimus blood levels, using the traditional strategy of monitoring only trough levels, for dosage individualization in liver transplant patients. Forty patients treated with tacrolimus after liver transplantation were studied during the early posttransplant phase (first 2 weeks). This phase was divided into four time periods (1-4 days, 5-7 days, 8-11 days, 12-14 days). Tacrolimus was administered twice daily. Approximately one determination of a tacrolimus trough level on whole blood was performed each day. The NPEM2 program was used to obtain population pharmacokinetic parameter values. With each individual pharmacokinetic parameter estimated by the MAP Bayesian method for a given period, the authors evaluated the prediction of future levels of tacrolimus for that patient for the next period. This evaluation of Bayesian fitting predictive performance was performed using the USC*PACK clinical software. Mean pharmacokinetic parameter values were in the same general range as previously published values obtained with richer data sets. However, during each period, the percentage of blood levels predicted within 20% did not exceed 40%. The traditional strategy of obtaining only trough whole blood levels does not provide enough dynamic information for the MAP Bayesian fitting procedure (the best method currently available) to be used for adaptive control of drug dosage regimens for oral tacrolimus. The authors suggest modifying the blood concentration monitoring scheme to add at least one other concentration measured during the absorptive or distributive phase to obtain more information about the behavior of the drug. D-Optimal design and similar strategies should be considered.

A population pharmacokinetic model of cyclosporine in the early postoperative phase in patients with liver transplants, and its predictive performance with Bayesian fitting.

The availability of personal computer programs to individualize drug regimens has stimulated interest in modeling population pharmacokinetics. This study used the NPEM2 software to determine cyclosporine population pharmacokinetic parameter values and distributions in a first group of 25 recipients of liver transplants during their first postoperative week. On a second group of 25 patients, the authors used these values to evaluate Bayesian predictive performance of cyclosporine blood concentrations with the USC*PACK PC program. During the study period, all the patients have been treated by continuous intravenous infusion. The one-compartment model pharmacokinetic parameter-the slope of volume to body weight (Vs) and the elimination rate constant (Kel) values found (mean values: Vs = 2.177 l/kg, Kel = 0.235 h(-1); median values: Vs = 1.559 l/kg, Kel = 0.163 h(-1); the percent coefficient of variation (Vs = 92%, Kel = 79%) appear reasonable and show the ability of NPEM2 to deal with sparse data. When the predictions were studied with day 1, day 2, or day 3 concentrations, predictive bias was respectively -0.030, -0.013, and 0.013 microg/ml, suggesting a greater clearance of cyclosporine immediately after surgery, the clearance decreasing in the days after. With the first three blood levels and the Bayesian fitting procedure, it was possible to predict at least half the subsequent measured blood levels of each patient accurately (within 20%) in more than three-quarters (76%) of the second group of recipients of transplants, and for 40% of patients the authors obtained accurate predictions in 100% of the subsequent blood levels. For a few patients (12%) they found quite poor predictions. The reason for this is unclear. The results suggest that this population model and the Bayesian fitting procedure using two or three blood levels can be reasonably and carefully used to control, in real time, cyclosporine blood levels in a majority of new patients with liver transplants.

Monitoring levels of human cytomegalovirus DNA in blood after liver transplantation.

We evaluated a semiquantitative PCR assay prospectively in 40 liver transplant recipients as an aid in making a prompt diagnosis of cytomegalovirus (CMV) infection. For 2 months after transplantation, clinical specimens from patients were tested weekly by PCR, virus isolation from peripheral blood and urine, and CMV serology. The incidence of active CMV infection was 70%. The levels of CMV DNA determined by hybridization of PCR samples and densitometric scanning of blots were assigned a score of 1 to 4 by comparison with four external standards amplified in parallel and corresponding to a range of 80 to 80,000 genomes. The first detection of CMV in blood by PCR occurred at a mean of 15 days, and high-level PCR scores of 3 or 4 were obtained 21 days after transplantation, whereas viremia occurred 33 days after transplantation. Significantly higher levels of CMV DNA were seen in patients with CMV disease (P < 0.05) than in asymptomatic patients. The prevalence of symptomatic CMV infection was 30%. The positive predictive value of PCR was 48%, while the negative predictive value was 100%. After treatment, the clearance of CMV DNA was always observed and the disappearance of symptoms occurred concomitantly with undetectable PCR signals.

Bone loss after orthotopic liver transplantation.

PURPOSE: We assessed changes in body composition and bone loss following liver transplantation to determine if bone loss is related to the underlying liver disease or to other factors such as sex, menopause, or graft rejection episodes. PATIENTS AND METHODS: Our cross-sectional study component compared bone mass and body composition in 31 patients at 1 year after liver transplantation versus 33 pregraft patients with chronic liver disease. Bone mass was measured by dual energy X-ray absorptiometry (DXA) using anteroposterior views of the total body to determine bone mineral content (BMC), and of the lumbar spine to assess bone mineral density (BMD). The body fat content was also determined by DXA. Radiographs of the thoracic and lumbar spine were also obtained. In our longitudinal study component, 16 patients from the pregraft group underwent bone mass assessment again 1 year after transplantation. RESULTS: Graft patients and pregraft patients both had reduced lumbar spine BMD compared to age- and sex-matched normal values (P < 0.001). A 4.75% increase in body fat content was observed after liver transplantation (P < 0.05). In the cross sectional study, bone mass of the spine and total body were not different in pre- and posttransplantation patients. However, the longitudinal study revealed significant decreases in spinal BMD and total body BMC, with a mean 3.5% decrease and a rate of loss of 0.55% per month. In addition, a dramatically high prevalence (29%) of vertebral fractures was observed in grafted patients, contrasting with a low prevalence (8.4%) of fractures in pregraft patients. Menopause, primary biliary cirrhosis, and chronic alcohol abuse were the principal contributing factors for osteoporosis. Patients with vertebral fractures had a marked 17.4% decrease of the lumbar spine BMD (P < 0.001) and a 22% decrease in total BMC when compared to patients without fractures (P < 0.01). CONCLUSION: Patients with orthotopic liver transplantation for chronic liver disease evaluated 1 year after transplantation have a high prevalence of vertebral fractures. Cross sectionally, bone mass was not different in patients before and after transplantation, but the longitudinal study showed that liver transplantation induced a marked and rapid bone loss. Bone loss due to transplantation could enhance the risk of new vertebral fractures, as shown by the high prevalence of vertebral fractures. These results emphasize the need to identify patients with low bone mass by bone densitometry before transplantation.

[Bypass for limb salvage. A matter of the veins? Preliminary report apropos of 100 femoro-distal revascularizations]. / Les pontages pour sauvetage de membre. Une question de veine? Rapport préliminaire à propos de 100 revascularisations fémoro-distales.

The authors have performed a prospective study on 100 cases of limb salvage. The reference procedure was the in situ femoro-subinguinal bypass (67 observations). If no vein could be used, replacement material was thin-wall PTFE (33 observations). Both groups are clinically and radiologically homogeneous. The longest delay is 30 months. The cumulated patency rate is 86% for venous bypass grafts against 62% for prostheses. The difference is less marked for limb salvage: 96% with venous bypass and 84% with a PTFE bypass. Without trying to oppose both techniques, the authors emphasize the need for revascularization, even when distally seems to be compromised.