Cost-effectiveness modeling of Dermagraft for the treatment of diabetic foot ulcers in the french context

To assess the cost-effectiveness of Dermagraft(R) (human dermal replacement) in the treatment of the diabetic foot ulcer, compared to standard treatment. A Markov model was developed, to simulate, over a 52-week period, the health status of a cohort of 100 patients with a diabetic foot ulcer treated either with conventional therapy or with Dermagraft(R). The considered health states were: healed, same site recurrence, unhealed not infected, cellulitis, osteomyelitis, amputation and death. Each week, the patient may progress among states according to a set of transition probabilities directly derived from the original clinical trial conducted in the USA. The cost of each health state was estimated by a Delphi panel of French diabetologists (direct costs only, valuated from a societal perspective). A sensitivity analysis was performed. The total number of healed ulcers included first ulcers healed (76.38% for Dermagraft(R) vs. 69.35% for standard treatment; median time to heal is 14-15 weeks for Dermagraft(R) compared with 28-29 weeks for standard treatment) plus recurrences which are subsequently healed within the 52-week period (14.29 for Dermagraft(R) vs. 25.09 for standard treatment; median time to heal is 3-4 weeks for Dermagraft(R) compared with 5-6 weeks for standard treatment). The average expected cost per treated patient (C/E) using standard treatment for the considered 52-week period is 47,418 FF vs. 54,384 FF for Dermagraft(R) (including 18,200 FF for Dermagraft(R) acquisition and 36,184 FF for standard treatment). Because Dermagraft(R) heals more ulcers within 52 weeks, the average cost per healed ulcer is lower (53,522 FF vs. 56,687 FF for standard treatment). The incremental cost-effectiveness ratio of Dermagraft(R) (DeltaC/DeltaE) equals 38,784 FF, indicating the extra investment that the decision-maker has to accept for an additional ulcer healed with Dermagraft(R) compared with conventional treatment.     

Trend of travelling times for haemodialysis patients in the Provence-Alpes-Côte-d'Azur region between 1995 and 2008

ObjectiveWe analysed the trend of travel-times for haemodialysis patients in the Provence-Alpes-Côte-d’Azur region between 1995 and 2008 in relation with the reforms concerning the health care provision of haemodialysis.MethodsWe conducted this study using data from three cross sectional surveys for 1995, 1999 and 2002, including all dialysis patients, and from the Renal Epidemiology and Information Network register for 2008. The data focuses on sociodemographic, medical characteristics and travel-times for haemodialysis patients.ResultsThe number of haemodialysis patients increased from 1807 patients in 1995 to 3141 in 2008. The travel-time has decreased steadily between 1995 and 2008 (18.2 min versus 15, P < 0.0001). The number of patients with a travel-time more than 45 min decreased from 7.2 to 3.5% between 1995 and 2008. The number of dialysis facilities has increased steadily between 1995 and 2008.ConclusionThe favorable trend in the health care provision has resulted in an improvement of accessibility by reducing travel-times.     

Experimental Infection of Peromyscus Species Rodents with Sin Nombre Virus

We demonstrate that 6 distinct Peromyscus rodent species are permissive to experimental infection with Sin Nombre orthohantavirus (SNV). Viral RNA and SNV antibodies were detected in members of all 6 species. P. leucopus mice demonstrated markedly higher viral and antibody titers than P. maniculatus mice, the established primary hosts for SNV.     

Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LC n –3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LC n –3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LC n –3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg⁻¹ h⁻¹ ( P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LC n –3PUFA induces greater activation ( P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg⁻¹ h⁻¹ ( P = 0.04) and oxidative metabolism was decreased ( P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism.     

Human lymphocyte adhesion to xenogeneic porcine endothelial cells: modulation by human TNF-α and involvement of VLA-4 and LFA-1

Considering that in the allogeneic situation the adhesion of recipient lymphocytes to donor endothelial cells initiates the cellular rejection, we questioned the possible occurrence of a similar process in the xenogeneic situation. The adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC) was thus studied in an in vitro porcine-to-human xenogeneic model. It was found that 25.9% of human PBL adhered to resting PAEC. Furthermore, this adhesion increased significantly when the PAEC were stimulated by the human cytokine TNF-α (tumor necrosis factor-α). The effect of human TNF-α was concentration- and time-dependent and was maximal (from 25.9% to 35.6%) with 100 U/ml during 6 h. Moreover, blocking experiments with monoclonal antibody (mAb) demonstrated the role of the PBL adhesion molecules LFA-1 and especially VLA-4. Indeed, an anti-CDl 1a mAb decreased PBL adhesion to resting PAEC by 17.1% and to TNF-α stimulated PAEC by 16.9%, whereas an anti-CD49d mAb decreased dramatically PBL adhesion to resting PAEC by 53.1% and to TNF-α stimulated PAEC by 41.0%. Finally, phenotypic analysis of the adherent PBL showed that 50.5% of adherent cells to resting PAEC were NK (natural killer) cells, whereas 50.7% of adherent cells to TNF-α stimulated PAEC were T lymphocytes, showing the preferential adhesion of NK cells to resting PAEC, and that the stimulation of the PAEC with human TNF-α affects predominantly T lymphocyte adhesion. These results indicate that human PBL could bind to xenogeneic PAEC and that this interaction could be a first step of xenogeneic cellular rejection.     

Follow-up after renal transplantation with organs from donors after cardiac death

Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study--Neoral-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline -1.3 ml/min DCD vs. -1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.