[Perception of medication risk by the public and role of the media]. / Rapport 22-09. Perception du risque médicamenteux par le public et rôle des médias.

Opinion polls regularly show that the vast majority of French people have a positive perception of the efficacy and safety of using medicines, including vaccines. Distrust or hostility towards them is only the fact of a small minority of the population, but active and noisy on social networks and overvalued by the media and public authorities. However, the pandemic due to Covid 19 (SARS-CoV-2) has confirmed to what extent the perception of drug risk by the public is unstable, sometimes irrational, how many and complex the determinants of this perception are and what role as a public resonance, fears play out in the media. We can even implicitly see the general underlying tendency of our society, which is to grant primacy to risk to the detriment of profit in the assessment of a technological innovation. The risk tree often masking the forest of efficiency. This polarization of minds on risks, associated with an overestimation of low probabilities, testifies to the impregnation of our mores by the ideology of precaution. To which are added distorting factors such as naturalistic prejudice, cultural relativism and the planetary extension of social networks which instantly spread false information that is more viral and better remembered than the true ones, hampering communication based on science data. Promoting the correct perception of drug risk requires recalling both the benefits and the risks linked to action but also those linked to inaction; to clarify institutional messages by making them as factual as possible; to limit the number of public broadcasters to achieve greater consistency in their messages; to have the frankness to sometimes say that we do not know, medicine by nature being practiced in a context of uncertainty. The Academy calls for an ambitious educational policy for young people: training in critical thinking and the acquisition of the basics of drug risk should be introduced from middle school. The Academy also believes that the public is entitled to expect quality-controlled information from the media, away from rumors, by calling on indisputable experts and by favoring objective data over subjective testimonies based on personal experiences.

Development and validation of a sensitive thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of phosgene in air samples.

A new rapid, sensitive and reliable method was developed for the determination of phosgene in air samples using thermal desorption (TD) followed by gas chromatography-mass spectrometry (GC-MS). The method is based on a fast (10 min) active sampling of only 1 L of air onto a Tenax® GR tube doped with 0.5 mL of derivatizing mixture containing dimercaptotoluene and triethylamine in hexane solution. Validation of the TD-GC-MS method showed a low limit of detection (40 ppbv), acceptable repeatability, intermediate fidelity (relative standard deviation within 12 %) and excellent accuracy (>95%). Linearity was demonstrated for two concentration ranges (0.04 to 2.5 ppmv and 2.5 to 10 ppmv) owing to variation of derivatization recovery between low and high concentration levels. Due to its simple on-site implementation and its close similarity with recommended operating procedure (ROP) for chemical warfare agents vapour sampling, the method is particularly useful in the process of verification of the Chemical Weapons Convention.

[Optimization of good use of medicinal products]. / Optimisation du bon usage du médicament.

Optimization of good use of medicinal products is aimed at allowing the patient to benefit fully from the efficacy of the prescribed treatment while limiting the negative impact of adverse effects. The prescriber and the dispensing pharmacist have an important complementary role crucial for the good use of medicinal products. This potential must be developed and improved. Patients' awareness should be reinforced, particularly be encouraging their dialogue with healthcare professionals. Improvement of the current situation can be based on self-appropriation of suitable information by each of the participants, leading to changing behavior. Common elaboration and diffusion of recommendations by the French National Academies of Medicine and Pharmacology would allow significant progress in good use of medicines.

Internationalization of regulatory requirements.

The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

[Compliance, efficacy and quality of life]. / Observance, efficacité et qualité de vie.

Compliance is the appropriateness of patient behaviour to therapeutic prescriptions. Good compliance increases treatment efficacy although its constraints may harm quality of life. Factors affecting compliance are related to the patient, the disease, health-care workers, family and treatment itself. Psycho-sociologic theories have attempted to explain patient behaviour. In clinical trials, compliance has to be optimized, i.e. in the protocol, during the study and the statistical analysis. In real life, compliance concerns all those involved in health-care, particularly for education, training and motivation of the patients and their immediate environment. Observational surveys relating to compliance are needed to determine prioriites and to develop a "compliance approach" based on improving information and the use of tools for better therapeutic adherence. Evaluation of the quality of life and patient satisfaction aspects is necessary to validate this approach.

[Communication and transparency concerning risk-benefit analysis in public health: the example of medication]. / Communication et transparence de l'évaluation du risque et bénéfice en santé publique: exemple du médicament.

As far as communication of the evaluation of risk benefit assessment of medications is concerned, validated and interpreted data only have to be taken into account. Free access to information by the public has to be considered seriously and there is now a real and strong demand. This situation has to be viewed in parallel with the huge development of websites communicating information on health issues. This report summarizes the discussion between the authorities and pharmaceutical companies and reports the different concrete proposals that emerged.

[Objectives and organization of the International Conference on Harmonization]. / Les fondements et l'organisation des conférences internationales sur l'harmonisation.

The objective of the International Conference on Harmonization established since 1989 is to allow marketing of new drugs as soon as possible for patient benefit. At the same time harmonization decreases development time by harmonizing the content and the format of the registration file in the three regions: European Union, United States and Japan. ICH is a unique process involving health authorities and industry representatives of the three regions. The Conference which took place in July 1997 was the end of the first step of the process. At the meeting it was decided to pursue this harmonization activity, particularly in initiating a project devoted to the file format (Common Technical Document). The current period will be essentially focused on implementation of the common Guidelines and on their update in relation to scientific progress, the major part of the file now being harmonized in its content.

The arterial wall: a new pharmacological and therapeutic target.

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.

[Arterial wall: a new pharmacological and therapeutic target?]. / La paroi artérielle: une nouvelle cible pharmacologique et thérapeutique?

In recent years, endothelial dysfunction and arterial remodelling in various cardiovascular diseases have emerged as two key concepts, with numerous interrelationships. Both endothelial dysfunction and arterial remodelling occur in various pathologies including heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extracellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extracellular matrix.

Hypothenar hammer syndrome: seventeen cases with long-term follow-up.

Hypothenar hammer syndrome is a rare and often incorrectly diagnosed form of secondary Raynaud's phenomenon in workers who use their hand as a hammer. We report 17 documented cases with long-term follow-up after diagnosis made on the basis of arteriography. Clinical findings include male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon. Angiography indicated that the 17 patients had either ulnar thrombosis or ulnar aneurysm; most of them also had embolic occlusions of the digital arteries. Main pathologic findings were thrombosis on the intima and fibrosis in the media. We adopted a surgical procedure consisting of resection with end-to-end reconstruction for patent aneurysms to avoid downstream emboli and more conservative treatment when the ulnar artery was thrombosed. No patient required digital amputation and all except one improved and were able to live and work normally with only a moderate disability, consisting of Raynaud's phenomenon during the cold season only.

[How to determine the optimal dosage of a drug]. / Comment déterminer la posologie optimale d'un médicament.

Determining the optimal dosage is an important step in the development of any drug, as it will provide a basis to demonstrate the effectiveness of that drug at different dosage levels. This determination is mainly attempted in phase II, notably by means of dose-response studies, but it is obvious that data obtained at every stage in the life of the drug will provide a better approach to dosage recommendations. Several examples are discussed.

[Industrial drug-surveillance]. / Pharmacovigilance industrielle.

Drug surveillance is a fundamental stake for the pharmaceutical industry. Drug manufacturers are responsible, both legally and morally, for the marketing of new products, and this represents very important investments. It is the duty and to the benefit of the pharmaceutical industry to set up a structure devised to collect and evaluate undesirable side-effects. In addition, drug surveillance may give rise to fruitful exchanges between scientific, teaching and industrial communities.