The “Health Benefit Basket” in France

The French “Health Benefit Basket” is defined principally by positive lists of reimbursed goods and services; however, global budget-financed hospital-delivered services are more implicitly defined. The range of reimbursable curative care services is defined by two coexisting positive lists/fee schedules: the Classification Commune des Actes Médicaux (CCAM) and the Nomenclature Générale des Actes Professionnels (NGAP). The National Union of Health Insurance Funds has been updating these positive lists since August 2004, with the main criterion for inclusion being the proposed procedure’s effectiveness. This is assessed by the newly created High Health authority (replacing the former ANAES). In addition, complementary health insurers are consulted in the inclusion process due to their important role in French healthcare financing

Cost-Effectiveness of Capping Freeways for Use as Parks: The New York Cross-Bronx Expressway Case Study

Objectives. To examine health benefits and cost-effectiveness of implementing a freeway deck park to increase urban green space. Methods. Using the Cross-Bronx Expressway in New York City as a case study, we explored the cost-effectiveness of implementing deck parks. We built a microsimulation model that included increased exercise, fewer accidents, and less pollution as well as the cost of implementation and maintenance of the park. We estimated both the quality-adjusted life years gained and the societal costs for 2017. Results. Implementation of a deck park over sunken parts of Cross-Bronx Expressway appeared to save both lives and money. Savings were realized for 84% of Monte Carlo simulations. Conclusions. In a rapidly urbanizing world, reclaiming green space through deck parks can bring health benefits alongside economic savings over the long term. Public Health Implications. Policymakers are seeking ways to create cross-sectorial synergies that might improve both quality of urban life and health. However, such projects are very expensive, and there is little information on their return of investment. Our analysis showed that deck parks produce exceptional value when implemented over below-grade sections of road

La prise en charge de la maladie d’Alzheimer dans les périphéries rurales des départements à dominante urbaine

L'objectif du projet Mapéru consistait à savoir s'il existait des formes de prises en charge professionnelles, des besoins et des trajectoires de la maladie d'Alzheimer spécifiques en milieu rural. Après vingt-quatre mois de recherche, le projet nous montre qu'à l'instar de son diagnostic, l'appréhension géographique de la maladie nous livre des réponses mais aussi des interrogations. La maladie d'Alzheimer est une maladie aux contours flous dont le diagnostic demeure probabiliste. Si à la faveur d'un effort politique, le diagnostic de la maladie en France présente sur le versant de l'offre une organisation et un maillage effectif (Ankri, 2013), les investigations mettent clairement en avant des décalages avec les besoins. En effet, la reconnaissance de la maladie d'Alzheimer ne se limite pas aux centres de diagnostic. Le projet nous montre à ce sujet, que contrairement aux distances géographiques, le médecin généraliste ainsi que les configurations familiales et sociales influencent l'accès au diagnostic. Dans ce jeu, on est en droit de s'interroger sur les conséquences en matière de diagnostic de la maladie, de la faible proportion de généraliste par habitant en milieu rural. Les taux de reconnaissance de la maladie sont sans équivoque et surtout corrélés positivement à la présence des médecins généralistes. Dans le même temps, les configurations sociales et familiales apparaissent des variables trop fluctuantes en campagne pour garantir un niveau de recours au diagnostic élevé dans ces espaces. C'est la raison pour laquelle on peut se questionner sur l'écart de détection entre malades reconnus et les personnes malades non reconnues. Enfin les investigations nous montre les limites de prise en charge de la maladie dans les territoires ruraux d'étude. Disposant d'un niveau élevé d'équipement médico-social, les territoires ruraux d'étude affichent dans le même temps un faible degré de spécialisation Alzheimer. Cette faible spécialisation est la résultante d'une coopération professionnelle déséquilibrée (concentration des liens vers les structures hospitalières locales et régionales) et d'une faible capacité locale à répondre aux appels à projets du Plan Alzheimer régulés par les nouvelles Agences Régionales de Santé. Or, ces carences ne sont pas sans conséquence sur les prises en charges de la maladie et les trajectoires des malades comme le montrent les entretiens menés dans le territoire rural Ouest. Les investigations auprès des aidants mettent clairement en avant une prise en charge qui oscille entre domicile et établissements selon la progression de la maladie. Dans ce sens, les mécanismes sociologiques et familiaux de repli du malade et de son entourage ainsi que le faible niveau de spécialisation professionnelle en milieu rural constituent les deux problématiques qui actent une inadaptation partielle de la prise en charge de la maladie d'Alzheimer. - Lors des situations d'urgence (rupture d'aide au domicile), elle se traduit pour les malades les mieux entourés (ceux de l'échantillon) par une inadaptation temporaire de la prise en charge dans des unités de longue durée ou des soins de suite et réadaptation de structures hospitalières ou bien dans des établissements éloignés géographiquement de l'ancien cadre de vie. Après quelques semaines d'attentes, ces malades sont pris en charge dans une maison de retraite médicalisée locale dont les besoins augmentent et la professionnalisation du personnel et l'aménagement de l'espace face à la maladie s'avèrent limités. - Pour la poignée de situations les plus vulnérables sur le plan familial et social, les entretiens avec les aidants montrent que la maladie accroît la vulnérabilité du malade et de l'aidant conduisant à des situations de repli et d'isolement. Dans ce sens, les décalages épidémiologiques relatés nous questionne sur le niveau de ces configurations de vulnérabilité, particulièrement dans un contexte excentré sur le plan géographique et social

BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker

BCL2-family proteins have a central role in the mitochondrial apoptosis machinery and their expression is known to be deregulated in many cancer types. Effort in the development of small molecules that selectively target anti-apoptotic members of this family i.e., Bcl-2, Bcl-xL, Mcl-1 recently opened novel therapeutic opportunities. Among these apoptosis-inducing agents, BH3-mimetics (i.e., venetoclax) led to promising preclinical and clinical activity in B cell malignancies. However, several mechanisms of intrinsic or acquired resistance have been described ex vivo therefore predictive markers of response as well as mechanism-based combinations have to be designed. In the present study, we analyzed the expression of the BCL2-family genes across 10 mature B cell malignancies through computational normalization of 21 publicly available Affimetrix datasets gathering 1,219 patient samples. To better understand the deregulation of anti- and pro-apoptotic members of the BCL2-family in hematological disorders, we first compared gene expression profiles of malignant B cells to their relative normal control (naïve B cell to plasma cells, n = 37). We further assessed BCL2-family expression according to tissue localization i.e., peripheral blood, bone marrow, and lymph node, molecular subgroups or disease status i.e., indolent to aggressive. Across all cancer types, we showed that anti-apoptotic genes are upregulated while pro-apoptotic genes are downregulated when compared to normal counterpart cells. Of interest, our analysis highlighted that, independently of the nature of malignant B cells, the pro-apoptotic BH3-only BCL2L11 and PMAIP1 are deeply repressed in tumor niches, suggesting a central role of the microenvironment in their regulation. In addition, we showed selective modulations across molecular subgroups and showed that the BCL2-family expression profile was related to tumor aggressiveness. Finally, by integrating recent data on venetoclax-monotherapy clinical activity with the expression of BCL2-family members involved in the venetoclax response, we determined that the ratio (BCL2+BCL2L11+BAX)/BCL2L1 was the strongest predictor of venetoclax response for mature B cell malignancies in vivo

Genomic signature to guide adjuvant chemotherapy treatment decisions for early breast cancer patients in France: a cost-effectiveness analysis

IntroductionChemotherapy (CT) is commonly used as an adjuvant treatment for women with early breast cancer (BC). However, not all patients benefit from CT, while all are exposed to its short- and long-term toxicity. The Oncotype DX® test assesses cancer-related gene expression to estimate the risk of BC recurrence and predict the benefit of chemotherapy. The aim of this study was to estimate, from the French National Health Insurance (NHI) perspective, the cost-effectiveness of the Oncotype DX® test compared to standard of care (SoC; involving clinicopathological risk assessment only) among women with early, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC considered at high clinicopathological risk of recurrence.MethodsClinical outcomes and costs were estimated over a lifetime horizon based on a two-component model that comprised a short-term decision tree representing the adjuvant treatment choice guided by the therapeutic decision support strategy (Oncotype DX® test or SoC) and a Markov model to capture long-term outcomes.ResultsIn the base case, the Oncotype DX® test reduced CT use by 55.2% and resulted in 0.337 incremental quality-adjusted life-years gained and cost savings of €3,412 per patient, compared with SoC. Being more effective and less costly than SoC, Oncotype DX® testing was the dominant strategy.DiscussionWidespread implementation of Oncotype DX® testing would improve patient care, provide equitable access to more personalized medicine, and bring cost savings to the health system

BCLXL PROTAC degrader DT2216 targets secondary plasma cell leukemia addicted to BCLXL for survival

Secondary plasma cell leukemia (sPCL) is a rare form of aggressive plasma cell malignancy arising mostly at end-stage refractory multiple myeloma and consequently presenting limited therapeutic options. We analyzed 13 sPCL for their sensitivity to BH3 mimetics targeting either BCL2 (venetoclax) or BCLXL (A1155463) and showed that 3 sPCL were efficiently killed by venetoclax and 3 sPCL by A1155463. Accordingly, BH3 profiling of 2 sPCL sensitive to BCLXL inhibition confirmed their high BCLXL primed profile. While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. We demonstrated in human myeloma cell lines and sPCL that sensitivity to DT2216 strongly correlated with the sensitivity to A1155463. Interestingly, we showed that low doses of DT2216 (nM range) were sufficient to specifically degrade BCLXL after 48 hours of treatment, consistent with VHL expression, in all cell lines but irrespectively to DT2216 sensitivity. In myeloma cells, DT2216 induced apoptotic cell death and triggered BAX and BAK activation. In conclusion, our study demonstrated that patients with sPCL addicted to BCLXL, a small but a very challenging group, could potentially receive therapeutic benefit from DT2216. Clinical trials of DT2216 in this subset of sPCL patients are warranted

Economic benefits of methylmercury exposure control in Europe : monetary value of neurotoxicity prevention

© 2013 Bellanger et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods: Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results: The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions: These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial economic benefits in Europe, mainly in southern countries. Some data may not be entirely representative, some countries were not covered, and anticipated changes in mercury pollution all suggest a need for extended biomonitoring of human MeHg exposure.Exposure data were contributed from the DEMOCOPHES project (LIFE09 ENV/BE/000410) carried out thanks to joint financing of 50% from the European Commission programme LIFE + along with 50% from each participating country (see the national implementation websites accessible via http://www.eu-hbm.info/democophes/project-partners). Special thanks go to the national implementation teams. The COPHES project that provided the operational and scientific framework was funded by the European Community's Seventh Framework Programme - DG Research (Grant Agreement Number 244237). Additional exposure data were supported by the PHIME project (FOOD-CT-2006-016253) and ArcRisk (GA 226534). We are grateful to Yue Gao and colleagues for sharing Flanders exposure data from the Flemish Center of Expertise on Environment and Health, financed and steered by the Ministry of the Flemish Community. National exposure data from the 2006–2007 French national survey on nutrition and health (Etude Nationale Nutrition Santé) were made available by Nadine Fréry, French Institute for Public Health Surveillance. Data from the Norwegian Mother and Child Cohort Study (a validation sample) were kindly provided by Anne Lise Brantsæter, National Institute of Public Health, Oslo. The UK mercury data were obtained from the ALSPAC pregnancy blood analyses carried out at the Centers for Disease Control and Prevention with funding from NOAA (the US National Oceanographic and Atmospheric Administration). The studies in the Faroe Islands were supported by the US National Institutes of Health (ES009797 and ES012199). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies

Childhood lead exposure in France: benefit estimation and partial cost-benefit analysis of lead hazard control

<p>Abstract</p> <p>Background</p> <p>Lead exposure remains a public health concern due to its serious adverse effects, such as cognitive and behavioral impairment: children younger than six years of age being the most vulnerable population. In Europe, the lead-related economic impacts have not been examined in detail. We estimate the annual costs in France due to childhood exposure and, through a cost benefit analysis (CBA), aim to assess the expected social and economic benefits of exposure abatement.</p> <p>Methods</p> <p>Monetary benefits were assessed in terms of avoided national costs. We used results from a 2008 survey on blood-lead (B-Pb) concentrations in French children aged one to six years old. Given the absence of a threshold concentration being established, we performed a sensitivity analysis assuming different hypothetical threshold values for toxicity above 15 μg/L, 24 μg/L and 100 μg/L. Adverse health outcomes of lead exposure were translated into social burden and economic costs based on literature data from literature. Direct health benefits, social benefits and intangible avoided costs were included. Costs of pollutant exposure control were partially estimated in regard to homes lead-based paint decontamination, investments aiming at reducing industrial lead emissions and removal of all lead drinking water pipes.</p> <p>Results</p> <p>The following overall annual benefits for the three hypothetical thresholds values in 2008 are: €22.72 billion, €10.72 billion and €0.44 billion, respectively. Costs from abatement ranged from €0.9 billion to 2.95 billion/year. Finally, from a partial CBA of lead control in soils and dust the estimates of total net benefits were € 3.78 billion, € 1.88 billion and €0.25 billion respectively for the three hypothesized B-Pb effect values.</p> <p>Conclusions</p> <p>Prevention of childhood lead exposure has a high social benefit, due to reduction of B-Pb concentrations to levels below 15 μg/L or 24 μg/L, respectively. Reducing only exposures above 100 μg/L B-Pb has little economic impact due to the small number of children who now exhibit such high exposure levels. Prudent public policies would help avoiding future medical interventions, limit the need for special education and increase future productivity, and hence lifetime income for children exposed to lead.</p