[Governance of drug advertising control: assessment of misleading advertising penalties]. / Gouvernance du contrôle de la publicité des médicaments: étude des modalités de sanction des publicités non conformes.

BACKGROUND: Loyal promotion of the pharmaceutical industry has been challenged by stakeholders. Drug advertising is the easiest point to assess. Based on the agency theory, our objective was to describe the governance of advertising control when it was misleading and the terms of penalties within the framework of the contradictory process between the industry and the regulatory authorities. METHODS: We conducted a thorough analysis of the contents of the minutes of the Board of Control of advertising from April 2007 to May 2010. The amounts of penalties were analyzed according to three criteria: the timing of the examination procedure (first session versus second session), the nature of the penalty (ban versus notice of change) and the company's defense strategy (written response versus presence of company representatives). RESULTS: Thirty-nine reports involving 62 projects to ban advertisements were analyzed. The first two causes of penalties were off label promotion and non-objective use of study results to support claims. The Committee issued 47 advertising bans (76%) and 15 formal notices of change (24%). When the defense strategy of the company involved the presence of representatives, there was a significant reduction of votes in favor of a ban (68% versus 81%, P<0.000). However, overall, the company's defense strategy did not influence the nature of the penalty (Chi(2)=2.05; P=n.s). CONCLUSION: These results should be put into perspective considering the fact that the qualitative composition of the commission was not free of potential conflicts of interest and that, moreover, only 10% of the penalty projects were reviewed. In addition, advertising control does not address the issue of the loyalty of the sales forces. Finally, our results open perspectives for research and managerial applications for the governance of advertising controls.

[Medical opinion leaders conflict of interests: effects of disclosures on the trust of the public and general practitioners]. / Conflits d'intérêts des leaders d'opinion médicaux : effets sur la confiance du grand public et des médecins généralistes.

BACKGROUND: Key medical opinion leaders influence the behaviors of physicians and patients. By law, they have to disclose their interests with pharmaceutical companies when they communicate in the media. Up to now, it appears that no study has explored the effect of opinion leaders' disclosures despite their potential impact on public health and economy. The study objective was to assess the effects of opinion leaders' disclosures of interest on the public and general practitioners' trust in opinion leader by comparison with the overall medical community. METHODS: In an experimental setting, three opinion leader profiles were built that differed only by the disclosure of their interests (hidden vs. weak vs. strong interests). One of the three profiles was randomly assigned to the subjects of two groups: 67 students and 60 general practitioners. According to an Anova analysis, the main effects and interactions of the disclosure of interests, of the message recipients, and of the assessed targets on the level of trust were measured. RESULTS: The results show that the average level of trust expressed by general practitioners was lower than that expressed by the general public. The level of trust in the opinion leader was lower than that of the overall medical community. The level of trust of exposed subjects fell much lower with stronger disclosed interests. While the general public did not distinguish trust between opinion leaders and the overall medical community, practitioners showed a significantly lower level of trust in opinion leaders with increasingly strong levels of disclosed interests. CONCLUSION: These study results refute the assertion that public trust would be reduced by the disclosure of interests. They reinforce the importance of the "who judges who" and "which kind of disclosure impacts who ?" effects and draw attention to further research on the role of social interactions in both mass and group communications.

Determination of urinary trans, trans-muconic acid reference values in general Tunisian population.

We wish to determine the urinary trans,trans-muconic acid reference values in the Tunisian general population, and evaluate the impact of several factors (age, gender, tobacco...) on these reference values. Urine samples were collected from 182 healthy Tunisian subjects who had not been occupationally exposed to benzene. This determination was performed by solid phase extraction sampling technique together with high performance liquid chromatography-photodiode array detector. Trans,trans-muconic values ranged from 0.003 to 0.618 mg/g creatinine, the 95% reference interval was: 0.004-0.36, and the 90% confidence interval of the upper reference limit was: 0.24-0.62 mg/g creatinine. Urinary trans,trans-muconic levels were significantly higher among smokers. Significant differences were also observed for the < 20 and the > or = 40 age groups. As a result urinary trans,trans-muconic background levels allow the biomonitoring of workers occupationally exposed to benzene at levels as low as 0.5 ppm. Age and tobacco, but not gender may affect the trans,trans-muconic reference values.

[Preliminary evaluation of a histocytological association predicted in a single sample of uterine exploration via a modified pipette: Mark II pipette]. / Evaluation préliminaire d'une association histo-cytologique prélevée en un seul geste pour exploration endo-utérine par une pipelle modifiée: la pipelle Mark II.

The pipelle has become the sampling tool of choice for histological detection of endometrial adenocarcinoma. Some practitioners still prefer cytological sampling. The distal extremity of the pipelle has been modified to allow removal of both types of samples simultaneously. The aim of this preliminary study was to evaluate the feasibility of this method. A positive agreement between histological and cytological results was found in 10 out of the 12 cases examined, among which an adenocarcinoma was positively detected. A prospective study on larger size must confirm these first findings. The new modified pipelle (Pipelle Mark II) offers a possible approach for reduction of false negatives.

[Folic acid supplementation by 200 microgram per day during the periconceptional period: a necessary public health approach to reducing incidence of spina bifida]. / La supplémentation en acide folique à 200 micrograms/j pendant la période périconceptionnelle: un comportement de santé publique nécessaire pour réduire l'incidence du Spina-bifida.

The incidence of neural tube closure abnormalities, and particularly Spina-bifida is correlated with a low dietary intake of folic acid, for which the marker is the erythrocyte folate concentration. Initially, preventive policies concerned women treated with anticonvulsant agents and those with a known family history of Spina-bifida. This constituted secondary prevention. The objective of this study was to demonstrate the methods and respective role of secondary and primary prevention in 1998. The evolution away from secondary prevention towards primary prevention, i.e. aimed at all women who intend to conceive has been based upon the fundamental epidemiological estimate that 95% of cases of Spina-bifida occur in babies born to women without a known family history of this type of disorder. The idea that dietary measures alone may suffice to ensure effective prevention is invalid. However, if used in addition to a mean dietary intake of 200 micrograms folic acid a day, the only use of pharmacological or synthetic supplementation of 200 micrograms/day makes it possible to achieve the desired threshold of Dietary Folate Equivalents of 600 micrograms/day. The dose of 200 micrograms/day has been judged by the authors as being the most effective and safe for use on a large scale in the general population. Today, in 1998, the primary prevention of neural tube closure abnormalities is the subject of an international consensus which recommends folate supplementation of 100 to 200 micrograms/day during the periconceptional period. Implementation of this solution in the context of a health education campaign would meet the expectations of many women, in as much as 66% of them have declared that they would be ready to comply with such primary preventive measures.

Minor and clinically non-significant interaction between toloxatone and amitriptyline.

The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small.

Debrisoquine and dextromethorphan phenotyping and antidepressant treatment.

The correlation between debrisoquine and dextromethorphan oxidation polymorphism was studied in 16 depressed in-patients. There was a close correlation between both phenotypes (r = 0.81 p less than 0.0017). During a treatment with amitriptyline during two weeks there was no significant modification of the dextromethorphan polymorphism. In the same way, the association of amitriptyline and toloxatone during two other weeks did not change this polymorphism in a significant way, even if there was a non significant shift towards higher values of the dextromethorphan metabolic ratio.

[Sex hormones, physical work and glucose and lipid metabolism (author's transl)]. / Hormones sexuelles, exercise physique et métabolismes glucidique et lipidique chez le rat des deux sexes.

Physical work reduce insulinmia after glucose load, plasma cholesterol and triglycerides by intact rat at normal diet or diet enriched with sucrose, or beef fat, or both. By the male rat at normal diet or enriched with sucrose + beef fat castration increase insulin secretion. -1) Glycemia by those at work with diet rich in sucrose with or without beef fat, -2) Oestrogens increase triglyceridemia by castrated at diet rich in sucrose or beef fat but physical work suppress those increase. By the female at normal diet or enriched with sucrose and at recastration increase insulinemia after glucose load; castration increase insulinemia by female at work with diet enriched with beef fat or beef fat + sucrose. Castration increase the fall of triglyceridemia at work except by those at diet enriched with sucrose and those receiving testosterone and at diet enriched with sucrose + beef fat.

[Linoleic acid in nutritional balance: experimental studies]. / L'acide linoléique dans l'équilibre alimentaire: recherches expérimentales.

In the male rat a diet rich in beef fat facilitates the occurrence of hyperinsulinemia after a glucose load whereas fats rich in linoleic acid produce no such effect. The combination of saturated fat and saccharose facilitates the occurrence of hypertriglyceridemia in the male rat, no such effect is produced by the combination of fats rich in linoleic acid and saccharose. Linoleic acid prevents natrium chloride from provoking hypertriglyceridemia in male and in female rats subjected to a diet enriched in saccharose and fat. Estrogen-induced hypertriglyceridemia in castrated animals is strongly inhibited if the diet is rich in linoleic acid. Physical effort can prevent saccharose combined with saturated fats from inducing hypertriglyceridemia.