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We establish necessary and sufficient conditions for the existence and infinite divisibility of alpha-determinantal processes and, when alpha is positive, of their underlying intensity (as Cox process). When the space is finite, these distributions correspond to multidimensional binomial, negative binomial and gamma distributions. We make an in-depth study of these last two cases with a non necessarily symmetric kernel.; Nous établissons des conditions nécessaires et suffisantes d’existence et d’infinie divisibilité pour des processus ponctuels alpha-déterminantaux et, lorsque alpha est positif, pour leur intensité sous-jacente (en tant que processus de Cox). Dans le cas où l’espace est fini, ces distributions correspondent à des lois binomiales, négatives binomiales et gamma multidimensionnelles. Nous étudions de façon approfondie ces deux derniers cas avec un noyau non nécessairement symétrique.

Figure S1. Flow chart of included patients. Table S2. Table resuming patients â characteristics. Table S3. Table resuming adverse event data by first-line treatment. (DOCX 37 kb)

Objectives: The objective of this study was to describe treatment patterns, survival, healthcare use and costs in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. Research design and methods: We used the National Health Insurance (NHI) claims database for the Ile-de-France region to perform a retrospective cohort analysis of patients with mRCC treated by a first-line targeted therapy. Treatment naïve patients were identified combining the 10th revision of the International Classification of Diseases (ICD-10) codes (C64 & C77-C79) and a first prescription of targeted therapies. Descriptive analyses were performed on treatment patterns and patients’ characteristics. Progression Free Survival (PFS) and Overall Survival (OS) were determined using Kaplan-Meier actuarial survival analysis. All healthcare resource use and costs were estimated using per patient per month (PPPM) basis (€2016). Results: 327 treatment naïve patients with mRCC were included. Median follow-up was 13.4 months. Sunitinib accounted for 73% of first-line treatments. The most frequently observed treatment sequence for the first two lines was sunitinib-everolimus (16%; n = 137) and for the first three lines sunitinib-everolimus-axitinib (20%; n = 49). First-line PFS for sunitinib, everolimus, pazopanib, sorafenib and other was 8.7, 6.2, 10.7, 5.7 and 11.2 months, respectively. Median OS for patients treated by first-line sunitinib, everolimus, pazopanib, sorafenib and other was respectively 14.7, 8.1, 21.1, 8.9 and 14.0 months. From the NHI’s perspective, the mean PPPM was €5,546. The average PPPM in pre-progression was €5,597 as compared to €5,541 beyond progression of the disease. Oral targeted therapies accounted for 53% of the total PPPM. Conclusion: This descriptive study showed that the economic burden of mRCC is substantial with oral targeted therapies accounting for 53% of the PPPM. OS and PFS in real life are poorer than observed in clinical trials.

Objective To perform a cost-effectiveness analysis of skin antiseptic solutions (chlorhexidine-alcohol (CHG) versus povidone iodine-alcohol solution (PVI)) for the prevention of intravascular-catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) in France based on an open-label, multicentre, randomised, controlled trial (CLEAN). Design A 100-day time semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN database. This model includes eight health states and probabilistic sensitivity analyses on cost and effectiveness were performed. Costs of intensive care unit stay are based on a French multicentre study and the cost-effectiveness criterion is the cost per patient with catheter-related bloodstream infection avoided. Patients 2,349 patients (age≥18 years) were analyzed to compare the 1-time CHG group (CHG-T1, 588 patients), the 4-time CHG group (CHG-T4, 580 patients), the 1-time PVI group (PVI-T1, 587 patients), and the 4-time PVI group (PVI-T4, 594 patients). Intervention 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) compared to 5% povidone iodine-69% ethanol (povidone iodine-alcohol). Results The mean cost per alive, discharged or dead patient was of €23,798 (95% confidence interval: €20,584; €34,331), €21,822 (€18,635; €29,701), €24,874 (€21,011; €31,678), and €24,201 (€20,507; €29,136) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. The mean number of patients with CRBSI per 1000 patients was of 3.49 (0.42; 12.57), 6.82 (1.86; 17.38), 26.04 (14.64; 42.58), and 23.05 (12.32; 39.09) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. In comparison to the 1-time PVI solution, the 1-time CHG solution avoids 22.55 CRBSI /1,000 patients, and saves €1,076 per patient. This saving is not statistically significant at a 0.05 level because of the overlap of 95% confidence intervals for mean costs per patient in each group. Conversely, the difference in effectiveness between the CHG-T1 solution and the PVI-T1 solution is statistically significant. Conclusions The CHG-T1 solution is more effective at the same cost than the PVI-T1 solution. CHG-T1, CHG-T4 and PVI-T4 solutions are statistically comparable for cost and effectiveness. This study is based on the data from the RCT from 11 French intensive care units registered with www.clinicaltrials.gov (NCT01629550).

The objective of this thesis is to conceptualize, starting from the exploitation of the refunding data of cares from the Sickness insurance, the various trajectories of cares recourses introduced by chronic diseases as asthma, and to study their determinants by analysing the profile and the subsequent behavior of the general practitioner. The study of the relation between the prescriptive behavior and the trajectory of cares is carried out by different multivariate analyses. The other objective is to evaluate, from a pharmacoeconomic point of view, the impact of the general practitioner characteristics on the various trajectories of cares followed by the patients with chronic diseases. The characteristics likely to identify a typology of practitioners correspond to the variables influencing the prescriptive behavior (age, sex, duration of exercise, type of exercise, etc). The principal question of the thesis is that of the regulating effect of the economic incentive, rested on the coordinated care pathway (reform of the Sickness insurance, August 2004), on the trajectories of cares, really observed by the chronic patients. The corollaries are: Does the no-reimbursement of some medical acts, not considered in the coordinated care pathway, have a significant impact on the empirical recourse of the patient? Does the profile of the general practitioner have an effect on the respect or not of the allowed trajectory of cares classified by the French reform? Which are the principal determinants of disregarding this referential trajectory, by notably analysing the “practitioner - patient” characteristics?, L’objectif de cette thèse est de conceptualiser, à partir de l’exploitation des données de remboursement de soins de l’Assurance Maladie, les différentes trajectoires de recours aux soins relatives à la prise en charge d’une pathologie chronique (asthme), et d’étudier les déterminants de ces trajectoires du point de vue du profil et du comportement subséquent du prescripteur de soins. L’étude de la relation entre le comportement prescriptif et la trajectoire de soins est appréhendée par des techniques de modélisation et d’analyses multivariées. L’objectif sous-jacent est d’évaluer, d’un point de vue médico-économique, l’impact de la typologie des prescripteurs (caractéristiques des offreurs de soins) sur les différentes trajectoires de soins suivies par les patients atteints de la pathologie définie supra. Les caractéristiques susceptibles d’identifier une typologie de prescripteur correspondent aux variables influant sur le comportement prescriptif, au sens large, du médecin (âge, sexe, durée d’exercice, type d’exercice, etc.). La question principale de la thèse est celle de l’effet régulateur de l’incitation économique, instaurée par le parcours de soins coordonnés (réforme de l’Assurance Maladie, août 2004), sur les trajectoires de soins, réellement observées, de patients atteints de pathologies chroniques. Les corollaires sont : Le déremboursement des actes hors parcours de soins coordonnés peut-il avoir un impact significatif sur la trajectoire empirique de prise en charge du patient ? Le profil du prescripteur d’actes médicaux a-t-il, toutes choses égales par ailleurs, un effet sur le respect ou non de la trajectoire de soins référentielle admise par le parcours de soins coordonnés ? Quels sont les déterminants principaux du non respect de cette trajectoire référentielle, du point de vue de l’analyse des caractéristiques des couples « médecin – patient» ?

National audience; The multi-state Markov model is a useful way of describing a process in which an individual moves through aseries of states in continuous time. The msm package for R allows a general multi-state model to be fitted to longitudinaldata. The progression of chronic diseases is often described by stages of severity. Features of msm include the ability tomodel transition rates between these different stages. The observations of the state Si(t) are made on a number of individualsi at arbitrary times t, which may vary between individuals. The interest of this paper is to specify the contribution of themulti-states modeling R package for pharmacoeconomics, in a health strategy assessment view.; Le modèle de Markov multi-états est une méthode pertinente pour décrire un processus dynamique de répartitiond’une cohorte d’individus vers une série d’états de santé, en temps continu. La librairie « msm » du logiciel R (multi-statemodel) autorise la création d’un modèle multi-états pour ajuster des données longitudinales. La progression d’une maladiechronique est souvent décrite par des stades de sévérité ; les spécificités principales de la librairie « msm » incluent lapossibilité de modéliser les probabilités de transition entre ces différents stades. Les observations de l’état Si(t) sont fondéessur la répartition d’un nombre d’individus i à un temps arbitraire t, lequel varie d’un patient à l’autre. L’intérêt de ce papierest de spécifier l’apport de la modélisation dynamique multi-états à l’évaluation médico-économique des stratégies de santé,notamment par l’adaptation des routines « msm » du logiciel R.

Background and objectives Education is a key component of the care of diabetic patients. Back in 1999 we set up a network for the management of diabetics which is centred on an out-of-hospital structured therapeutic patient education (TPE) programme Its main objective is to help improve the patient9s state of health. Programme The TPE programme comprises three parts (a total of 27 h) and is implemented by trained professionals (doctors, dieticians, chiropodists, nurses) in an out-of-hospital setting. An external assessment using standards established by the French National Authority for Health (HAS) was performed from 2005 to 2007. Analysis focused on items in the patient9s file (blood pressure (BP), glycated haemoglobin (HbA1c), LDL cholesterol), health professional and patient satisfaction surveys, a quality of life questionnaire (DHP 81), and reimbursements by French national health insurance. The data were compared to the results of the 2001 ENTRED study. Results The analysis concerned 268 patients with type 2 diabetes (mean age, 65.2 years; 55.2% male). The disease had been diagnosed on average 12.1 years earlier and 31.4% of patients were on insulin. There was no difference beween our population and the ENTRED population. The satisfaction score was 8.9/10 and 6.9/10 for network patients and professionals, respectively, versus 8.4/10 and 6.4/10, respectively, for ENTRED patients and professionals. The quality of life score was 6.7/81 versus 16.3/81 for ENTRED. Annual eye examinations were performed in 83.3% of network patients versus 66.9% of ENTRED patients. At least three HbA1c measurements were made in 71% of network patients versus 51.5% of ENTRED patients. Over the three parts, an HbA1c of Discussion and conclusion The impact of the network was highly positive with regard to patient satisfaction and quality of life but less so with regard to health professional satisfaction. Working within a network helps improve professional practices. The network provides educational value for patients independently of any care they receive and this can be translated into better clinical and biological test results. The health economics analysis confirmed that the expenditure incurred by the network was offset by savings in terms of direct health expenditure. A limitation of our study was that the ENTRED study is a little outdated. In conclusion, educational support provided independently of care is effective. Contexte, objectifs La prise en charge des patients diabetiques est pluridisciplinaire et l9education est un element essentiel. Des 1999 nous avons mis en place un reseau de prise en charge des diabetique centre sur un programme structure educatif ambulatoire: le Reseau Vichy Diabete dont l9objectif principal est de faciliter l9amelioration de l9etat de sante des patients. Programme Le programme d9education therapeutique est realise en ambulatoire en 3 cycles (soit 27 heures), par des professionnels formes (medecins, dieteticiens, podologues, infirmieres). Une evaluation externe repondant au referentiel de l9HAS a porte sur la periode de fonctionnement 2005 a 2007 et a inclus 268 patients diabetiques. L9analyse a porte sur les parametres du dossier (HTA,HbA1c, LDL), des enquetes de satisfaction professionnels et patients, un questionnaire qualite de vie (DHP 81), l9analyse des depenses remboursees par l9assurance maladie. Les donnees obtenues sont comparees aux resultats de l9etude ENTRED realisee en 2001. Resultats La population est diabetique de type 2 dont 31.4% traites par insuline. L9age moyen est de 65.2 ans (55.2% sont des hommes), l9anciennete du diabete de 12.1 ans. Il n9y pas de difference avec la population ENTRED. La note de satisfaction des patients reseau est de 8.9/10 et des soignants 6.9/10 vs 8.4/10 et 6.4/10 pour ENTRED. Le score qualite de vie est de 6.7/81 vs 16.3/81. 71% des patients reseau ont eu au moins 3 dosages d9HbA1c par an vs 51.5 pour ENTRED. 83.3% vs 66.9% ont eu un FO annuel. L9HbA1c evolue favorablement au fil des cycles, 30.1% des patients en cycle 1, 36.3% en cycle 2 et 42.6% en cycle 3 ont une HbA1c Discussion/conclusion L9impact de la prise en charge reseau est tres positive sur la satisfaction et la qualite de vie des patients mais moins sur celle des professionnels. Le fonctionnement en reseau ameliore les pratiques professionnelles et demontre l9interet d9une prise en charge educative y compris sur les resultats cliniques et biologiques des patients. Par contre la reference comparative de l9etude ENTRED est probablement un peu ancienne. L9analyse economique confirme que les depenses engendrees par le reseau sont compensees par une economie en terme de depense directe de sante. Une prise en charge educative independamment du soin, demontre son efficience.