Fine-scale geographic variations of rates of renal replacement therapy in northeastern France: Association with the socioeconomic context and accessibility to care.

BACKGROUND: The strong geographic variations in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease are not solely related to variations in the population's needs, such as the prevalence of diabetes or the deprivation level. Inequitable geographic access to health services has been involved in different countries but never in France, a country with a generous supply of health services and where the effect of the variability of medical practices was highlighted in an analysis conducted at the geographic scale of districts. Our ecological study, performed at the finer scale of townships in a French area of 8,370,616 inhabitants, investigated the association between RRT incidence rates, socioeconomic environment and geographic accessibility to healthcare while adjusting for morbidity level and medical practice patterns. METHODS: Using data from the Renal Epidemiology and Information Network registry, we estimated age-adjusted RRT incidence rates during 2010-2014 for the 282 townships of the area. A hierarchical Bayesian Poisson model was used to examine the association between incidence rates and 18 contextual variables describing population health status, socioeconomic level and health services characteristics. Relative risks (RRs) and 95% credible intervals (95% CrIs) for each variable were estimated for a 1-SD increase in incidence rate. RESULTS: During 2010-2014, 6,835 new patients ≥18 years old (4231 men, 2604 women) living in the study area started RRT; the RRT incidence rates by townships ranged from 21 to 499 per million inhabitants. In multivariate analysis, rates were related to the prevalence of diabetes [RR (95% CrI): 1.05 (1.04-1.11)], the median estimated glomerular filtration rate at dialysis initiation [1.14 (1.08-1.20)], and the proportion of incident patients ≥ 85 years old [1.08 (1.03-1.14)]. After adjusting for these factors, rates in townships increased with increasing French deprivation index [1.05 (1.01-1.08)] and decreased with increasing mean travel time to reach the closest nephrologist [0.92 (0.89-0.95]). CONCLUSION: These data confirm the influence of deprivation level, the prevalence of diabetes and medical practices on RRT incidence rates across a large French area. For the first time, an association was found with the distance to nephrology services. These data suggest possible inequitable geographic access to RRT within the French health system.

Advanced kinetic analysis as a tool for formulation development and prediction of vaccine stability.

We have used a protein-based vaccine, a live virus vaccine, and an experimental adjuvant to evaluate the utility of an advanced kinetic modeling approach for stability prediction. The modeling approach uses a systematic and simple procedure for the selection of the most appropriate kinetic equation to describe the degradation rate of compounds subjected to accelerated conditions. One-step and two-step reactions with unlimited combinations of kinetic models were screened for the three products under evaluation. The most appropriate mathematical model for a given product was chosen based on the values of residual sum of squares and the weight parameter w. A relatively simple n-th order kinetic model best fitted the degradation of an adjuvanted protein vaccine with a prediction error lower than 10%. A more complex two-step model was required to describe inactivation of a live virus vaccine under normal and elevated storage temperatures. Finally, an autocatalytic-type kinetic model best fitted the degradation of an oil-in-water adjuvant formulation. The modeling approach described here could be used for vaccine stability prediction, expiry date estimation, and formulation selection. To the best of our knowledge, this is the first report describing a global kinetic analysis of degradation of vaccine components with high prediction accuracy.

Geriatric oncology, general practitioners and specialists: current opinions and unmet needs.

PURPOSE: To describe the patterns of care of elderly cancer patients (ECPs) (>70 years old) and the factors affecting the referral by general practitioners (GPs) of patients to cancer specialists (SPs), in Alsace France. METHODS: A postal mail questionnaire was sent to a total of 2818 physicians including primary care physicians and specialists. The factors possibly responsible for a poor referral rate of ECPs and the factors affecting treatment implementation by specialists were explored. We also searched for unmet needs such as the incorporation of geriatric assessment into routine practice and continuous medical education (CME) programs. RESULTS: A total of 1217 questionnaires were returned (46.9%) from 1053 GPs and 214 SPs. Patients' age did not negatively impact referral to SPs as opposed to patients' performance status, wishes, and co-morbidities. Conversely, a significant decrease in patients' file presentation by SPs to tumor boards was observed for patients over 80 years old. Neither reimbursement nor SPs' waiting lists were an issue. The need for CME programs in geriatric oncology was emphasized by both GPs and SPs. CONCLUSIONS: Age was not the governing variable that impacted patient referral. The need for CME in geriatrics was highlighted for both GPs and SPs.

Health indicators in the European regions--ISARE II.

BACKGROUND: Most comparisons of health data in Europe take place at the national level. However, there is increased interest in looking at health data at a sub-national level. This is because of the increased importance in many European countries, of regions and devolved powers to them. This study aimed to establish the availability of health data at a regional level and to construct an experimental database. METHODS: Using a network of country correspondents, data were collected on a series of topics from all the regions of that country. In addition, a supplementary list of data was collected from one region of each country. RESULTS: Out of the then 15 Member States of the European Union (EU), 14 countries participated in the study. Thirteen countries were able to supply data. Where data were available, using the criteria we developed, these were of relatively good quality. Data on mortality was most readily available, but data on the important public health topics such as obesity was much more difficult to obtain, and absent in many cases. CONCLUSIONS: It is possible to construct a database and a resultant set of indicators for relevant sub-national areas of Member States in the EU. This is not likely to be achieved through current routine data collection systems unless significant changes are made to the data collection processes such as those undertaken by Eurostat. There is, also, an urgent need to introduce comprehensive sub-national data collections on important public health topics such as obesity and smoking.

Effect of efflux inhibition on brain uptake of itraconazole in mice infected with Cryptococcus neoformans.

Itraconazole is a fungistatic agent that, although highly lipophilic, shows poor transport through the blood brain barrier that may be due to efflux proteins. The combined administration of an efflux inhibitor with itraconazole should increase cerebral itraconazole concentrations and therefore, improve the treatment of Cryptococcus neoformans meningitis with this antifungal agent. To test this hypothesis, we have studied the influence of murine cerebral infection with C. neoformans and the inhibition of efflux by intraperitoneal injection of a P-glycoprotein inhibitor, GF120918 [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl)9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide], on the pharmacokinetics of itraconazole in plasma and brain after a single intraperitoneal itraconazole injection. We also investigated the influence of efflux inhibition on the efficacy of repeated doses of itraconazole in this murine model. The results showed that in healthy and infected mice pretreated or not with GF120918, plasma itraconazole values of area under the curve (AUC) were similar. In contrast, cerebral values of AUC were higher in infected mice compared with healthy mice. Moreover, the pretreatment of infected mice with GF120918 significantly increased cerebral itraconazole values of area under the curve and decreased weight loss in the treatment with itraconazole of a cerebral infection with C. neoformans.