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Objectives: To our best knowledge, no study in France has comprehensively investigated the prehospital history of patients admitted for severe cases of COVID-19. 'Patients' voice is an excellent means to capture data on primary care pathways. We aimed to identify clusters of COVID-19 hospitalised patients with similar prehospital symptom sequences, and to test whether these clusters were associated with a higher risk of poor clinical outcomes. Design: Cross-sectional online survey using life-event calendars. Setting: All patients hospitalised for COVID-19 between September 2020 and May 2021 in the Infectious Disease Departments in Nice and in Marseilles in France. Participants: 312 patients responded to the survey. Main outcome measures: From the day of symptom onset to the day of hospitalisation, we defined a symptom sequence as the time-ordered vector of the successive symptom grades (grade 1, grade 2, grade 3). State sequence analysis with optimal matching was used to identify clusters of patients with similar symptom sequences. Multivariate logistic regressions were performed to test whether these clusters were associated with admission to intensive care unit (ICU) and COVID-19 sequelae after hospitalisation. Results: Three clusters of symptom sequences were identified among 312 complete prehospital pathways. A specific group of patients (29%) experienced extended symptoms of severe COVID-19, persisting for an average duration of 7.5 days before hospitalisation. This group had a significantly higher probability of being admitted to ICU (adjusted OR 2.01). They were less likely to know a loved one who was a healthcare worker, and more likely to have a lower level of education. Similarly, this group of patients, who were more likely to have previously visited the emergency room without exhibiting severe symptoms at that time, may have been inclined to postpone reassessment when their health worsened. Their relatives played a decisive role in their hospitalisation. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between maternal gestational Vitamin D3 supplementation and early respiratory health in offspring. This was a population-based record-linkage study which used data from the French National Health Database System. Maternal Vitamin D3 supplementation consisted of a single high oral dose of cholecalciferol, (100,000 IU) from the seventh month of pregnancy, according to national guidelines. In total, 125,756 term-born singleton children were included, of which 37% had respiratory illness defined as hospital admission due to respiratory causes or inhalation treatment up to 24 months of age. Infants prenatally exposed to maternal Vitamin D3 supplementation (n = 54,596) were more likely to have a longer gestational age (GA) at birth (GA 36–38 weeks, 22% vs. 20%, p < 0.001 in exposed vs. non-exposed infants, respectively). After adjusting for the main risk factors (maternal age, socioeconomic level, mode of delivery, obstetrical and neonatal pathology, birth weight appropriateness, sex, and birth season), the risk of RD was found to be 3% lower than their counterparts (aOR [IC 95%], 0.97 [0.95–0.99], p = 0.01). In conclusion, this study provides evidence for the association between maternal gestational Vitamin D3 supplementation and improved early respiratory outcomes in young children. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1°) sociodemographic and clinical profile of their patients considered as depressed 2°) patterns of care provision. Methods The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder. Results Compared to patients identified as depressed by GPs, those identified by psychiatrists were younger, more often urban (10.5% v 5.4% – OR = 2.4), educated (42.4% v 25.4% – OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% – OR = 2.9), had been hospitalized for depression (26.1% v 15.6% – OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). Conclusion Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear to reflect more the organization of the French care system than the competence of providers.

Introduction: Children with Autism Spectrum Disorders (ASDs) have problems with social skills. Social skills training groups are among the proposed therapeutic strategies, but their efficacy still needs to be evaluated. Objective: To evaluate the efficacy of an implicit social skills training group in children with ASDs without intellectual disability. Methods: A before-and-after study of children with ASD without intellectual disability was conducted in a child psychiatry day hospital, where they participated in an implicit group with cooperative games. Their social skills were assessed using the Social-Emotional Profile (SEP), the Childhood Autism Rating Scale (CARS), and the empathy quotient (EQ) before and after 22 weeks. Results: Six patients aged 9 to 10 years old were evaluated. A significant increase in overall adaptation and social skills (median 8 and 7.7 points) in the SEP was demonstrated in addition to a significant reduction in the CARS score (median: 4 points), including in the field of social relationships. The EQ increased two-fold. Discussion—Conclusion: This implicit group improved the children’s social skills. It would be interesting to evaluate the maintenance of these skills over time, examine more widespread results, and compare implicit and explicit groups. [ABSTRACT FROM AUTHOR]

Background: A prospective study was conducted to evaluate the impact of an educational reproductive health program on medical student peer educators and the secondary school pupils whom they taught. Methods: The Marseille School of Medicine and ten public secondary schools participated in the study. Medical students were recruited and trained as peer educators to promote sexual health in the secondary schools. The medical students and secondary school pupils were evaluated before and after education program. The main outcome measure was the sexual health knowledge score on a 20-item questionnaire (maximum score 20). Results: A total of 3350 students attended the peer-led course conducted by 107 medical students. The medical students' score increased significantly before and after the course (from 15.2 ± 1.8 to 18.3 ± 0.9; p < 0.001). The knowledge score of the pupils increased (from 7.8 ± 4 to 13.5 ± 4.4; p < 0.001). The girls' score was significantly higher than the boys' score after the course, but not before (14.5 ± 3.3 vs 12.5 ± 4.6; p < 0.001). Prior to the course, the score among the female medical students was significantly higher than that of the males. The overall knowledge increase was not significantly different between medical students and secondary school pupils (mean 3.1 ± 1 and 5.7 ± 4 respectively; p > 0.05). Conclusions: The program was effective in increasing the knowledge of medical students as well as secondary school pupils. Male sexual health knowledge should be reinforced. [ABSTRACT FROM AUTHOR]

Background: Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1°) sociodemographic and clinical profile of their patients considered as depressed 2°) patterns of care provision. Methods: The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder. Results: Compared to patients identified as depressed by GPs, those dentified by psychiatrists were younger, more often urban (10.5% v 5.4% - OR = 2.4), educated (42.4% v 25.4% - OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% - OR = 2.9), had been hospitalized for depression (26.1% v 15.6% - OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). Conclusion: Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear o reflect more the organization of the French care system than the competence of providers. [ABSTRACT FROM AUTHOR]

Devant l’ampleur des investissements de l’industrie pharmaceutique et les risques financiers encourus par celle-ci, il est important pour les firmes pharmaceutiques de protéger au mieux leurs inventions par de multiples techniques et ce, pendant une longue période. Les brevets appliqués aux molécules sont un moyen de protection temporaire, à ces derniers brevets peuvent s’ajouter des brevets additionnels ou brevets secondaires. Enfin le certificat complémentaire de protection constitue aussi un moyen juridique de protection des brevets de médicaments. Une autre méthode, exclusive cette fois-ci de référence juridique, permet d’étendre la durée de protection des brevets de médicaments, c’est l’inversion chirale. Mots clés : propriété intellectuelle, brevet pharmaceutique, durée de protection, brevet additionnel, certificat complémentaire de protection, inversion chirale Abstract Pharmaceutical research constitutes a significant cost for pharmaceutical companies. Because of the importance of the financial investment in research projects, companies must protect their discoveries. There are multiple ways to do this. First, the legal avenue can be divided into three parts: a pharmaceutical company can protect a new drug by a patent, then an additional patent or a secondary patent; moreover, since 1992 in Europe, the pharmaceutical industry has been able to extend a patent by the “Supplementary Protection Certificate” (le Certificat Complémentaire de Protection [CCP]). The nonjuridical way is to use the chiral “switch”, which can extend patents close to expiring, thus enhancing profitability. Keywords: intellectual property, drug patent, patent’s term, additional patent, supplementary protection certificate, chiral switch Texte reçu le 28 octobre 2003 ; accepté le 9 février 2004 [ABSTRACT FROM AUTHOR]

Introduction : Le but de cet article est de présenter une synthèse bibliographique sur la méthodologie et les effets sur l’humeur du test de déplétion en tryptophane. Méthode : Nous avons fait une recherche Medline de 1985-2002 autour des mots clés « tryptophan depletion » et « mood ». Résultats : La déplétion aiguë est obtenue par l’ingestion le matin à jeun d’un mélange d’acides aminés exempt de tryptophane. Les sujets présentant une prédisposition familiale aux troubles dépressifs ainsi que les patients dépressifs traités par une molécule potentialisant la neurotransmission sérotoninergique présentent une altération plus ou moins importante de l’humeur. En revanche, les effets sont limités, voire inexistants, chez les sujets sains et les patients dépressifs naïfs de tout traitement. Conclusion : Le test de déplétion en tryptophane a largement contribué à la compréhension de la physiopathologie dépressive, mais il ne peut actuellement être utilisé comme modèle de dépression chez le sujet sain. Mots clés : déplétion en tryptophane, sérotonine, dépression, humeur, antidépresseur Abstract Introduction: This paper focuses on the methodology and behavioural results of the tryptophan depletion challenge. Methods: A Medline search (1985-2002) using the keywords ‘tryptophan depletion’ and ‘mood’ has been performed. Results: Rapid depletion is obtained by morning intake under fasting condition of a tryptophan-free amino-acid mixture. Subjects with a family history of mood disorders and depressed patients receiving serotoninergic drugs demonstrate a mood-lowering effect. However, these effects are limited or absent in normal volunteers and naive depressed patients. Conclusion: The tryptophan depletion challenge has largely contributed to the understanding of the physiopathology of depression. However, the mood response to acute tryptophan depletion challenge in healthy volunteers is not as sensitive as a ‘depression model’. Keywords: tryptophan depletion, serotonin, depression, mood, antidepressant treatment Texte reçu le 17 juin 2002 ; accepté le 11 février 2003 [ABSTRACT FROM AUTHOR]

Le hoquet se définit comme une contraction spasmodique du diaphragme déterminant une brusque secousse de l’abdomen et du thorax. Dans la littérature disponible, quelques médicaments sont retrouvés à l’origine de ce symptôme. Nous rapportons trois observations après administration de benzodiazépine à des sujets sains jeunes, durant deux essais cliniques. Dans la première étude (un essai de bioéquivalence entre deux formes galéniques, comprimés et solution orale), 12 sujets ont été inclus dans un essai en ouvert, contrôlé, randomisé avec deux périodes séparées par un « washout » de 7 jours. Deux sujets ont présenté un hoquet après l’administration de 2 mg de lormétazépam (solution orale). Les symptômes ont régressé en 10 et 40 minutes respectivement. Chez un sujet, la réintroduction avec le comprimé de lormétazépam a été positive. L’objectif de la deuxième étude était d’évaluer les effets d’une privation de sommeil et de la sédation induite par le lorazépam sur les mouvements oculaires saccadiques chez 12 sujets sains. Un hoquet est apparu chez un sujet, 3 h 15 après l’administration de lorazépam (2 mg) et a régressé en 45 minutes. Toutes ces observations ont été évaluées avec la méthode d’imputabilité française et discutées à la lumière des classes de médicaments le plus souvent mentionnés dans la littérature. Mots clés : hoquet, benzodiazépine, essais cliniques Abstract Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. In the literature, some drugs have been reported to induce hiccup. We discuss three case reports after administration of benzodiazepine to healthy young subjects during two clinical trials. In the first study (a bioequivalence trial of two forms of lormetazepam, tablets and oral solution), 12 subjects were included in an open controlled crossover study with two periods separated by a washout of 7 days. Two subjects presented with hiccup after administration of lormetazepam (2mg oral solution). The symptom resolved in 10 and 40 minutes, respectively. In one subject, rechallenge with a tablet of lormetazepam was positive. The aim of the second study was to assess the effect of sleep deprivation and lorazepam-induced sedation on saccadic eye movements in 12 healthy subjects. Hiccup occurred in one subject 3h 15 after administration of a single oral dose of lorazepam (2mg) and resolved in 45 minutes. All cases were evaluated according to the French imputation method. These observations are discussed with regard to the drug classes mentioned most frequently in the literature. Keywords: hiccup, benzodiazepine, clinical trials Texte reçu le 9 février 2004 ; accepté le 29 avril 2004 [ABSTRACT FROM AUTHOR]

Introduction: Children with Autism Spectrum Disorders (ASDs) have problems with social skills. Social skills training groups are among the proposed therapeutic strategies, but their efficacy still needs to be evaluated., Objective: To evaluate the efficacy of an implicit social skills training group in children with ASDs without intellectual disability., Methods: A before-and-after study of children with ASD without intellectual disability was conducted in a child psychiatry day hospital, where they participated in an implicit group with cooperative games. Their social skills were assessed using the Social-Emotional Profile (SEP), the Childhood Autism Rating Scale (CARS), and the empathy quotient (EQ) before and after 22 weeks., Results: Six patients aged 9 to 10 years old were evaluated. A significant increase in overall adaptation and social skills (median 8 and 7.7 points) in the SEP was demonstrated in addition to a significant reduction in the CARS score (median: 4 points), including in the field of social relationships. The EQ increased two-fold., Discussion—conclusion: This implicit group improved the children's social skills. It would be interesting to evaluate the maintenance of these skills over time, examine more widespread results, and compare implicit and explicit groups.

Background: Male infertility related to professional reprotoxic exposure has been assessed in several studies. Collaboration between occupational physicians and patients can yield information about the preventive measures that can be taken to avoid such exposure. The use of preventive measures is determined by the collaboration between reproductive medicine and occupational medicine and also by the patient's awareness of reprotoxic occupational exposures. Our andrology laboratory developed a systematic environmental interview that an occupational physician administers before semen analysis to assess patients' occupational reprotoxic chemical and physical exposures. This observational prospective study evaluated patients' feelings regarding this interview. The main outcome measure was the participants' score to determine their general reprotoxicant knowledge. The study also evaluated the patients' satisfaction about the interview with occupational physician and their attitude about reproductive toxicants., Results: The mean score for general knowledge of reprotoxicants was 9.6 ± 2.7/16. The most frequently underestimated reprotoxic factor was excessive heat (34.7 % correct responses). In cases of semen parameter abnormalities AND recognized occupational reprotoxic exposure, 63.2 % of the patients said they would use individual protective devices, and 55.1 % said they would temporarily adapt their workstation. Regarding the interview with the laboratory's occupational physician, 80.7 % considered it moderately or very useful. Of the interviewed patients, 46.2 % reported having changed their living habits 2 months after the interview, and 88.5 % were satisfied or very satisfied with the care they received. All of the respondents said it would be useful to extend the interview to include their wives., Conclusions: The data suggest that patients' knowledge about reprotoxic exposures can be improved, particularly knowledge related to physical exposure. The vast majority of patients were satisfied with the introduction of this new collaboration between reproductive and occupational medicine.

Objectives: To assess the impact of continuous incident reporting and subsequent prevention strategies on the incidence of severe iatrogenic events and targeted priorities in admitted neonates., Methods: We performed preintervention (January 1 to September 1, 2005) and postintervention (January 1, 2008, to January 1, 2009) prospective investigations based on continuous incident reporting. Patient-safety initiatives were implemented for a period of 2 years. The main outcome was a reduction in the incidence of severe iatrogenic events. Secondary outcomes were improvements in 5 targeted priorities: catheter-related infections; invasive procedures; unplanned extubations; 10-fold drug infusion-rate errors; and severe cutaneous injuries., Results: The first and second study periods included totals of 388 and 645 patients (median gestational ages: 34 and 35 weeks, respectively; P = .015). In the second period the incidence of severe iatrogenic events was significantly reduced from 7.6 to 4.8 per 1000 patient-days (P = .005). Infections related to central catheters decreased significantly from 13.9 to 8.2 per 1000 catheter-days (P < .0001), as did exposure to central catheters, which decreased from 359 to 239 days per 1000 patient-days (P < .0001). Tenfold drug-dosing errors were reduced significantly (P = .022). However, the number of unplanned extubations increased significantly from 5.6 to 15.5 per 1000 ventilation-days (P = .03)., Conclusions: Prospective, continuous incident reporting followed by the implementation of prevention strategies are complementary procedures that constitute an effective system to improve the quality of care and patient safety.

Ketamine, an antagonist N-Methyl-D-Aspartate receptor, induces a broad range of anomalies in healthy subjects similar to those observed in psychosis. Previous studies have shown that information sensorimotor processing was impaired in patients with schizophrenia. The aim of the study was to assess the effects of subanesthetic doses of ketamine on behavior symptoms and information processing in healthy volunteers. A double-blind, crossover, placebo-controlled study was performed with eight subjects. Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Scale for the Assessment of Positive Symptoms assessed behavior changes. Information processing was assessed using a choice reaction time. Three experimental factors (stimulus intensity, stimulus response compatibility, and foreperiod duration) chosen to affect a different stage of information processing were manipulated. Our study has demonstrated that administration of ketamine produced significant effects on Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Scale for the Assessment of Positive Symptoms scores. Results on choice reaction time demonstrated a significant longer reaction time under ketamine. Effects of stimulus intensity and compatibility stimulus response were similar under ketamine and under placebo. Moreover, there was a specific interaction between ketamine and foreperiod. This interaction indicated that foreperiod's effect was more prolonged under ketamine (29 ms) than under placebo (17 ms). These results showed that the clinical effects of ketamine were associated with schizophrenic-like impairments on choice reaction time in healthy subjects.