[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.

Effect of local urokinase on arterial occlusion of lower limbs.

Sixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 patients showed that local arterial plasminemia occurred in only 1 patient. Local urokinase does not strongly stimulate "endogenous" thrombolysis and enhances "exogenous" thrombolysis only very inconstantly. A better adaptation of urokinase dosage or the use of an agent with higher affinity for fibrin might improve the efficiency of local thrombolytic therapy.

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.

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.

Hemodynamic evaluation of hypotension during chronic hemodialysis.

Hypotensive episodes occur frequently during hemodialysis; they are often sudden and difficult to prevent despite careful clinical control. Their etiology was studied by investigating the hemodynamic response of five patients submitted to ultrafiltration during their three first dialyses. A Swan Ganz catheter was inserted and left in position for 5 days. Simultaneous determination of cardiac output, mean pulmonary artery (PAP) and capillary and systemic arterial pressures were recorded. 10 hypotensive episodes were observed. In 3 patients in whom the first hypotensive episode occurred 10 minutes after the start of dialysis, there was a significant drop in PAP, cardiac index and stroke index while heart rate and peripheral resistance remained unchanged. Paradoxical bradycardia was observed. In 4 patients hypotension was observed more than one hour after initiation of dialysis. Before the hypotensive episode there was moderate elevation of heart rate and peripheral resistance and an insignificant reduction in PAP. Cardiac index and stroke index were diminished. The decrease in MAP was only 2 mm Hg. Hypovolemia is the most important factor in hemodialysis-induced hypotension but other factors such as vagal stimulation, autonomic neuropathy and osmotic disequilibrium can interfere with blood pressure control and trigger hypotension. Methods of preventing hypotension during dialysis, including the infusion of low molecular weight dextran, are discussed.

Local urokinase in arterial thromboembolism.

Selective intra-arterial urokinase (UK) is effective in treating recent arterial thromboembolism. However, usually only partials lysis is achieved and this treatment seems less effective than intravenous streptokinase. At a dose of 37,500 UCTA/hour it does not produce systemic fibrinolysis. This protocol substantially reduces the risk of systemic bleeding and embolism and extends its applicability to operative patients. The combination of surgery and UK seems particularly promising in patients with atherosclerotic arterial thrombosis.

[Cardiac amyloidosis: clinical, x-ray, electric, hemodynamic, developmental and pathological aspects. Apropos of 85 cases collected from French cardiology departments]. / L'amylose cardiaque: aspects cliniques, radiologiques, électriques, hémodynamiques, évolutifs et anatomiques. A propos de 85 cas réunis dans les services de cardiologie français.

85 cases of cardiac amyloidosis have been collected from the university cardiac departments of France. Four distinct clinical pictures have emerged: 1. Primary cardiac amyloidosis (36 cases) which combines: congestive cardiac failure, ECG signs (extreme axis deviation, low voltage, signs of myocardial necrosis), arrhythmias (67%), and a rapidly fatal outcome (23.2 m +/- 8.5); 2. Cardiac amyloidosis associated with a marked neuromuscular amyloidosis (8 cases), in patients of Portuguese extraction (4 out of 8), with a positive family history (6 out of 8), characterised by arrhythmias (5 out of 8), and with a better prognosis (1 death out of 8); 3. Cardiac amyloidosis associated with a dysglobulinaemia (14 cases) with a clinical picture which is almost identical with that of primary cardiac amuloidosis; 4. Senile cardiac amyloidosis, whose frequency increases with age, may sometimes be discovered at routine post mortem examination, and is characterised by atrial fibrillation (13 out of 27) and its association with anaemia, signs of inflammation, and coronary atheroma.

[Course and prognostic factors of unstable angina. Apropos of 100 cases]. / Evolution et facteurs pronostiques de l'angor instable. A propos de 100 cas

The immediate and medium term (3 years) of unstable angors was specified by the study of 100 hospitalized patients. The cases selection was based on the existence of angina pain which had appeared or reappeared less than a month before, during more than fifteen minutes and/or repeated, which were more and more frequent, less and less sensitive to nitroglycerine, and in the absence of recent myocardial infarction signs. The immediate course seemed relatively favorable; during the initial hospitalisation there were only nine myocardial infarctions and three deaths. The alarming factors of initial prognosis are essentially the persistence or recurrence under medical treatment of angina pain hardly relieved by nitroglycerine. The course over three years was bad; 23.6% of deaths, especially of cardiac origin (14/17) were noted; more than 80% or the surviving patients kept enduring more or less severe pains; persistence of electric signs on the ECG during the initial course was the only significant pronostic factor that was regularly noted. As regards the 16 patients treated by surgery, operative death rate remained high (3/16), but remote functional results were good (8/12 asymptomatic). Only randomized studies on homogenous groups, carried out during an enough long course, will enable us to specify therapeutic indications better.

[Severe ischemia of the lower limbs after ingestion of LSD]. / Ischémie sévère des membres inférieurs après ingestion de LSD.

A case of severe limb ischaemia predominating in the legs in a young female drug addict is reported. Arteriography revealed diffuse spasm of all arteries of the lower limbs associated with localised spasm along the profunda artery in particular. These appearances regressed on control angiography performed 10 days later. The treatment which associated volume expanders and intravenous vasodilatation agents (magnesium sulphate) led to rapid improvement in the clinical condition in 3 days. There were no long-term complications. The causative role of LSD was suggested by the history of greatly increased intake in the period before the onset of symptoms. LSD is a derivative of lysergic acid, the common nucleus of the derivative of the ergot of rye. Analysis of a sample dose taken by the patient showed a very large quantity of LSD and of lysergic acid and a very small amount of other ergot alkaloids known for their peripheral vasoconstrictor effects. The circumstances following peripheral ischaemia are discussed; the association of haschich - LSD does not seem to be a factor. The increased doses and a predisposed vascular system, in common with ergot containing drugs, seem to be the major factors.

[Thombosis of a persistent sciatic artery: a rare cause of severe ischemia in the lower limb (author's transl)]. / Thrombose d'une artère sciatique persistante. Une cause rare d'ischémie sévère d'un membre inférieur.

Persistence of the primitive axial limb artery is an uncommon developemental anomaly. This artery is called sciatic in account of its connections with the nerve. Usually gluteal aneurysms develop and the anomaly is disclosed by a complication : pain, pulsatile buttock mass, thrombosis or release of emboli. Prophylactic surgical repair of such aneurysms seems reasonable.

[Evaluation of the spread of atherosclerosis in patients with arteritis. Implications for the therapeutic indications (author's transl)]. / Bilan de la diffusion de l'athérosclérose chez l'artéritique. Conséquences sur les indications thérapeutiques.

The immediate prognosis (operative risk of a revascularization) and also the long-term prognosis for the patient with arteritis depends on the spreading of the atheroma to other vascular regions (coronary or carotid arteries). Conventionally the initial evaluation is made by cervical Doppler examination, effort ECG and profile aortography. Cervical Doppler examination revealed in the present group of 402 patients significant stenoses on the arterial vessels leading to the brain in 67 cases (16.6%), including 13 asymptomatic stenoses. The effort ECG carried out in 140 cases was assurable in 72% of these, being positive in 19% of the cases in patients with no clinical or ECG history of coronary insufficiency. Profile aortography of 125 patients revealed atheromatous lesions in 39 (31%), in many cases multiple lesions: 13 cases in the coeliac trunk and mesenteric artery. The implications of these discoveries, as they affect therapeutic indications and in particular the justification of multiple revascularizations, have been discussed.

[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.

[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.

[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.

[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.

[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.