[Horizon scanning in preparation for future health threats: a pilot exercise conducted by the French Institute for Public Health Surveillance in 2014]. / La veille prospective, une démarche de préparation aux futures menaces de la santé publique : exercice mené à l'Institut de veille sanitaire en 2014.

Background: Health surveillance is a reactive process, with no real hindsight for dealing with signals and alerts. It may fail to detect more radical changes with a major medium-term or long-term impact on public health. To increase proactivity, the French Institute for Public Health Surveillance has opted for a prospective monitoring approach.Methods: Several steps were necessary: 1) Identification of public health determinants. 2) Identification of key variables based on a combination of determinants. Variables were classified into three groups (health event trigger factors, dissemination factors and response factors) and were submitted to future development assumptions. 3) Identification, in each of the three groups, of micro-scenarios derived from variable trends. 4) Identification of macro-scenarios, each built from the three micro-scenarios for each of the three groups. 5) Identification of issues for the future of public health.Results: The exercise identified 22 key variables, 17 micro-scenarios and 5 macro-scenarios. The topics retained relate to issues on social and territorial health inequalities, health burden, individual and collective responsibilities in terms of health, ethical aspects, emerging phenomena, 'Big data', data mining, new health technologies, interlocking of analysis scales.Conclusions: The approach presented here guides the programming of activities of a health safety agency, particularly for monitoring and surveillance. By describing possible future scenarios, health surveillance can help decision-makers to influence the context towards one or more favourable futures.

Profiling the active site of a copper enzyme through its far-infrared fingerprint.

Vibrations of the metal active site of the Cu,Zn-superoxide dismutase enzyme were analyzed by far-infrared difference spectroscopy and theoretical normal mode calculation. Both electrochemically triggered Cu(I) and Cu(II) redox states show well-defined infrared vibrational modes, notably modes of the histidine ligands, the Cu(II)-His(61)-Zn(II) bridge and of the water pseudo-ligand.

Theoretical study of the gas-phase reactions of iodine atoms ((2)P(3/2)) with H(2), H(2)O, HI, and OH.

The rate constants of the reactions of iodine atoms with H(2), H(2)O, HI, and OH have been estimated using 39, 21, 13, and 39 different levels of theory, respectively, and have been compared to the available literature values over the temperature range of 250-2500 K. The aim of this methodological work is to demonstrate that standard theoretical methods are adequate to obtain quantitative rate constants for the reactions involving iodine-containing species. Geometry optimizations and vibrational frequency calculations are performed using three methods (MP2, MPW1K, and BHandHLYP) combined with three basis sets (cc-pVTZ, cc-pVQZ, and 6-311G(d,p)). Single-point energy calculations are performed with the highly correlated ab initio coupled cluster method in the space of single, double, and triple (pertubatively) electron excitations CCSD(T) using the cc-pVnZ (n = T, Q, and 5), aug-cc-pVnZ (n = T, Q, and 5), 6-311G(d,p), 6-311+G(3df,2p), and 6-311++G(3df,3pd) basis sets. Canonical transition state theory with a simple Wigner tunneling correction is used to predict the rate constants as a function of temperature. CCSD(T)/cc-pVnZ//MP2/cc-pVTZ (n = T and Q), CCSD(T)/6-311+G(3df,2p)//MP2/6-311G(d,p), and CCSD(T)/6-311++G(3df,3pd)//MP2/6-311G(d,p) levels of theory provide accurate kinetic rate constants when compared to available literature data. The use of the CCSD(T)/cc-pVQZ//MP2/cc-pVTZ and CCSD(T)/6-311++G(3df,3pd) levels of theory allows one to obtain a better agreement with the literature data for all reactions with the exception of the I + H(2) reaction R(1) . This computational procedure has been also used to predict rate constants for some reactions where no available experimental data exist. The use of quantum chemistry tools could be therefore extended to other elements and next applied to develop kinetic networks involving various fission products, steam, and hydrogen in the absence of literature data. The final objective is to implement the kinetics of gaseous reactions in the ASTEC (Accident Source Term Evaluation Code) code to improve speciation of fission transport, which can be transported along the Reactor Coolant System (RCS) of a Pressurized Water Reactor (PWR) in case of a severe accident.

Relative effectiveness assessment of listed drugs (REAL): a new method for an early comparison of the effectiveness of approved health technologies.

OBJECTIVES: Post-listing assessment of pharmaceuticals depends on national habits. In England, the assessment is based on estimates of cost per quality-adjusted life-year. These are made some considerable time after listing (negative list). In France, effectiveness, and then efficiency, is assessed immediately after listing (positive list). We propose a new formal method--the REAL method--that can help make early comparisons of the effectiveness of medical treatments. METHODS: Relative efficacies are first obtained from randomized controlled trials (RCTs). Members of the Transparency Committee (French National Authority for Health) are then consulted by questionnaire on the transposability of these results to real life. The RCT results and experts' ratings are entered into an effect model to obtain estimates of relative effectiveness, using unidimensional scaling, and bootstrap procedures. RESULTS: Application of the REAL method to the example of a new drug to treat Parkinson's disease and three comparators used in the same indication provided graphs of the distributions of their relative efficacy and relative effectiveness. The new drug was found to provide no added value. CONCLUSIONS: The REAL method is a rational, transparent, and practical procedure for comparing the effectiveness of pharmaceuticals in an immediate post-listing setting.

Vibrational modeling of copper-histamine complexes: metal-ligand IR modes investigation.

Recent reports on proteins and related models show that vibrational spectroscopy in the far-infrared domain is a promising technique to characterize metal sphere coordination in proteins. The low-frequency modes are however complex, and there is a need to develop the analysis of metal sites by means of quantum chemical calculations as a support for useful interpretation of the far-IR data. In this study, we determined vibrational properties for systems containing Cu(II)-N(Imidazole) interactions present in many biological complexes by means of quantum chemical calculations and confronted the normal mode description with available experimental data. Analysis of the [Cu(histamine)]2+ complex led us to conclude that the anharmonic contributions are negligible in the far-IR domain. Geometry optimizations and vibrational frequency calculations of [Cu(hm)]2+ and [Cu(hm)2(ClO4)2] complexes were compared using various hybrid DFT functionals and basis sets. These investigations stressed the need of potential energy distribution calculations (PED) to assign the vibrational modes, to obtain an overall description of the vibration modes, and to efficiently compare the methods. Comparison of calculation methods with the B3LYP/6-31+G(d,p) and B3LYP/6-311+G(2d,2p) methods and with available experimental data showed that the B3LYP/6-31G(d,p) level of theory provides accurate predictions of the normal mode frequencies and assignments. These comparisons also enlighten that theoretical investigations of 2H- and 65Cu-labeled [Cu(hm)2(ClO4)2] complexes give with a very good accuracy the band shifts of the labeled copper-histamine derivatives. The theoretical calculations combined with experimental data allowed us to predict and calculate with good accuracy the values and assignments of the low-frequency IR modes, notably those involving metal contribution.

National Authority for Health: France.

The French National Authority for Health (Haute Autorité de Santé, or HAS) was established to assist France's public institutions in optimizing the basket of reimbursable goods and services and to help health care professionals continuously improve their clinical practice by defining best-care standards and identifying relevant tools and methods. HAS carries out single technology assessment (STA) and multiple technology assessment (MTA), assessing both the intrinsic benefit of the new technology and its effectiveness compared with that of existing technologies. A new treatment may not be covered unless it provides either improved benefit or lower cost, and STA is mandatory before a new drug, device, or medical procedure can be added to the benefit list for sickness funds. While HAS recommendations are advisory, the decision-making bodies (the Ministry of Health or the union of sickness funds) accept its findings in most cases.

Comparative effectiveness research and evidence-based health policy: experience from four countries.

CONTEXT: The discussion about improving the efficiency, quality, and long-term sustainability of the U.S. health care system is increasingly focusing on the need to provide better evidence for decision making through comparative effectiveness research (CER). In recent years, several other countries have established agencies to evaluate health technologies and broader management strategies to inform health care policy decisions. This article reviews experiences from Britain, France, Australia, and Germany. METHODS: This article draws on the experience of senior technical and administrative staff in setting up and running the CER entities studied. Besides reviewing the agencies' websites, legal framework documents, and informal interviews with key stakeholders, this analysis was informed by a workshop bringing together U.S. and international experts. FINDINGS: This article builds a matrix of features identified from the international models studied that offer insights into near-term decisions about the location, design, and function of a U.S.-based CER entity. While each country has developed a CER capacity unique to its health system, elements such as the inclusiveness of relevant stakeholders, transparency in operation, independence of the central government and other interests, and adaptability to a changing environment are prerequisites for these entities' successful operation. CONCLUSIONS: While the CER entities evolved separately and have different responsibilities, they have adopted a set of core structural, technical, and procedural principles, including mechanisms for engaging with stakeholders, governance and oversight arrangements, and explicit methodologies for analyzing evidence, to ensure a high-quality product that is relevant to their system.

Radiation-induced formation of DNA intrastrand crosslinks between thymine and adenine bases: A theoretical approach.

The role of local geometric and stereo-electronic effects in tuning the radiation-induced formation of intrastrand crosslinks between adenine and thymine has been analyzed by a computational approach rooted in density functional theory. Our study points out that together with steric accessibility, stereo-electronic effects play a major role in determining the reaction mechanism and the observed predominance of the thymine-adenine lesion over the opposite sequence isomer.

Overview of health technology assessment in France.

Health technology assessment (HTA) in France covers a variety of activities performed for different customers (e.g., health professionals in the field and policy makers in government) for the benefit of patients. To promote the improvement of quality in health care, France has set up a series of distinct agencies that report to the Ministry of Health but are also accountable to their other customers. We place particular emphasis on ANAES (National Agency for Accreditation and Evaluation in Health) whose main remit is HTA. We show how the diversity of HTA activities and their decentralization suggests tight collaboration among all the different bodies which perform HTA or are closely involved with HTA, and we provide examples of such collaboration.