[First French-speaking days of users of decision support system in clinical pharmacy: Feedback and perspectives]. / Premières journées francophones des utilisateurs de système d'aide à la décision en pharmacie clinique : retour d'expériences et perspectives.

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

CMRI based 3D left ventricle motion analysis on patients with acute myocardial infarction.

3D Quantitative measurement of left ventricle (LV) motion on patients with acute myocardial infarction has been recognized as essential for effective LV function diagnosis. This paper presents a method to quantify 3D LV motion obtained from conventional CINE MRI using image analysis based on mathematical modeling. Level set method is employed for segmentation, and a 3D LV geometry was reconstructed by co-registering different views of MRI images. A mathematical model of LV geometry was then constructed to quantitatively describe the LV wall inward motion. The results using real data show that the method is able to quantify the LV inward motion, and can clearly represent the changed motion pattern with the follow-up data. Furthermore, the LV motion analysis for 8 patients with acute myocardial infarction (MI) show that high inward motion occurs mainly in the basal region of LV while a negative relation is found between LV ejection fraction (EF) improvement after acute MI and solely basal region inward motion, which could be helpful for diagnosis and LV EF recovery prediction.

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatonin- agonist and selective 5HT2c receptors antagonist, in the treatment of major depressive disorders]. / Etude pilote comparant en aveugle l'effet thérapeutique de deux doses d'agomélatine, agoniste des récepteurs de la mélatonine et antagoniste des récepteurs 5HT2C, chez 30 patients présentant un épisode dépressif majeur.

RATIONALE AND METHOD: Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D-7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score < 15 or decrease > or = 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. RESULTS: Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p < 0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6 +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatments a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties in falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse events in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. CONCLUSION: Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a dose at least as effective and slightly better tolerated than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

[Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatoninergic agonist and selective 5HT2C receptors antagonist, in the treatment of major depressive disorders]. / Etude pilote comparant en aveugle l'effet thérapeutique de deux doses d'agomélatine - agoniste des récepteurs de la mélatonine et antagoniste des récepteurs 5HT2c - chez 30 patients.

Rational and method - Two doses of agomelatine (S-20098), a novel potential antidepressant drug with a new pharmacological profile (melatonin agonist and selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised, pilot study in order to estimate the antidepressant activity shown in preclinical data. Inpatients suffering from major depressive disorder (DSM III-R criteria) and presenting a minimal score of 25 for MADRS were selected at D -7. After one week of run-in placebo treatment, included patients received one evening dose of agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required at least for the first 3 weeks. Patients presenting a satisfying response to treatment (MADRS total score<15 or decrease 40% from inclusion score) could be treated as outpatients. A follow up of 2 weeks was performed after stopping the treatment. The total duration of the treatment period could vary, according to investigator's decision, between 7 and 11 weeks. Evaluation criteria included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when applicable, at D35, D42, D49 and D56. Safety evaluations included recording of adverse events, ECG monitoring and biology. Results - Thirty inpatients were selected and 28 included (14 per group). There was no major difference between groups at inclusion, neither for demographic nor evaluation criteria. One patient of each group was excluded of the ITT analysis; 19 patients completed the mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10 patients (5 in each group) carried on the study during the optional period, up to D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy criteria showed a significant improvement in both groups, with highly significant within group evolutions (p<0.001 whatever the criteria) and without significant difference between groups. However, better results were observed in the 5 mg group compared to the 100 mg group. Total MADRS scores then decreased from 30.7 3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the 100 mg group. Furthermore, significant improvement between D14 and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed with both treatment a strong decrease of symptoms during the study, especially for items related to sleep disorders (difficulties for falling asleep, interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability was good for both doses of agomelatine. However, there were slightly more emergent adverse events and severe treatment-related adverse event in the 100 mg group. No modifications of cardio-vascular parameters nor biological abnormalities were observed in both groups. Conclusion - Preliminary clinical data with agomelatine confirm the potential antidepressant effect in accordance with positive preclinical results. There was no significant difference between 5 and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg could be a at least as effective and slightly better tolerated dose than 100 mg. Further double-blind controlled studies versus active comparators and placebo are required in order to confirm these results.

[Trauma, traumatic stress and depression following an airline catastrophy]. / Traumatismes, stress traumatique, et dépression à la suite de catastrophes aériennes.

OBJECTIVES: Acute stress responses following a trauma indicate a sensitivity to posttraumatic stress disorder (PTSD), and is often comorbid with depression. Earlier exposure to a traumatic event can be an additional risk factor in PTSD development. METHOD: Eight injured patients hospitalized after a major air disaster were monitored and assessed for a month. The symptoms of acute stress response (ASR), PTSD, and depression were assessed using DSM-IV criteria immediately following the accident, then each week thereafter. The Impact of Event Scale (IES) was completed on the 30th day (D30). RESULTS: Four patients presented with an ASR, and 3 of them had a PTSD at D30. Of those 3 patients with PTSD, 2 presented with an associated depression. These 2 patients had been exposed to a traumatic event before the disaster; and a significant relation was found between the history of the earlier trauma and the PTSD associated with depression. CONCLUSION: The traumatized victims with a history of earlier traumas seem more susceptible to developing a PTSD associated with depression.

[Acute peri-traumatic dissociative experiences: assessment and course]. / Troubles dissociatifs aigus péritraumatiques: évaluation et évolution.

Previous research has identified acute stress symptoms, particularly peri-traumatic dissociative symptoms (the distortion of consciousness, depersonalization, derealization, automatic movements, flashbacks with illusions or hallucinations), as risk factors for the development of later posttraumatic stress disorder. Numerous retrospective assessments and current prospective studies confirm these findings. It is suggested that peri-traumatic dissociation be assessed immediately after traumatic exposure and during the weeks following. But traumatized victims may present other categories of acute reactions; panic attacks, acute depression, conversion reaction, excessive emotional expression, and psychotic reactions. Brief reactive psychosis is a major differential diagnosis with peri-traumatic dissociative experiences. During emergency interventions it may be difficult to distinguish between dissociative and psychotic symptoms. It is cautioned that these disorders be evaluated with a follow-up of several months.

Does the short variant of the serotonin transporter linked polymorphic region constitute a marker of alcohol dependence?

The serotonin (5-hydroxytryptamine: 5-HT) system has been thought to play an important role in several steps of alcohol craving. A number of studies, including our own, have reported that alcohol dependence is associated with dysfunction of 5-HT transmission. Pharmacological and clinical studies have shown that the 5-HT transporter (5-HTT) and the 5-HT1A receptor appear to be candidate loci for the aetiology of alcohol dependence. We have analysed the presence of different 5-HTT and 5-HT1A variants in 104 alcohol-dependent patients and 38 controls for a possible association with alcohol dependence. In alcohol-dependent patients, we found a high frequency of the S allele of 5-HTTLPR (45.5% vs. 29%, chi2 = 6.33, p = 0.0081). No other significant differences were observed between the two populations for other polymorphisms. These results provide, for the first time, preliminary evidence that alcohol abuse disorders are associated with a genetic variant for 5-HT transmission. It might be possible to use this detection of the "S" allele as a clinical tool for pathology diagnosis and to advise recovering alcoholics and it could represent an aid to the prevention of relapse. Therapeutic actions could be envisaged to use this genotyping to help select the best therapeutic strategy.

[Psychotic disorders and syphilitic meningoencephalitis with arterial involvement]. / Troubles psychotiques et méningo-encéphalite syphilitique avec participation artéritique.

A propos of the beginning of a serious psychotic disorder at the abatement of a cerebral vascular accident, clinical, paraclinical and psychometric developments during one year after treatment permits an analysis of the relation between the syphilitic meningo-encephalitis and the mental disorder.