[Predictive factors of seclusion duration in patients hospitalized in psychiatry settings. A prospective multisite study in the DTRF Paris-Sud]. / Facteurs prédictifs de la durée d'isolement chez les patients hospitalisés en psychiatrie. Une étude prospective multicentrique au sein du DTRF Paris-Sud.

INTRODUCTION: In psychiatric inpatient settings seclusion is a last resort to ensure the safety of the patient, other patients, and staff from disturbed behaviors. Despite its major interest for patients, seclusion could negatively impact treatment adherence and patient/staff relationships. Indeed, some secluded patients report a feeling of guilt during the measure and do not consider seclusion to be a healthcare intervention. To be more beneficial and to reduce the feeling by patients of being forced, seclusions should be as short and rare as possible. In other words, measures to reduce seclusion are available and have been clearly identified. Such measures could be applied, in the first instance, in patients with longer duration. In this way, the aim of this study was to investigate predictive factors of a seclusion of long duration. METHODS: Our study was based on the dataset of the EPIC study, an observational prospective French multicenter study of seclusion and restraint. The EPIC study occurred in seven French psychiatric hospitals in the southern region of Paris. Inclusions were realized for 73days and allowed a data collection of 302 seclusion measures. Of these measures 236 were effectively a seclusion in a standardized room. Because the median duration was 7days, we defined two groups of patients: duration<7days and duration ≥ 7 days. Our variable to be explicated was duration ≥ 7 days. Explicative variables available in EPIC study were age, sex, forced hospitalization, autoagressivity, heteroagressivity, use of sedative treatment (oral or intramuscular), history of seclusion and patient diagnoses. We used bivariate and multivariate analyses to explore the association between a seclusion duration ≥ 7 days and explicative variables. Diagnoses were classified as psychotic disorders, mood disorders and others diagnoses. To be included in multivariate logistic regressions, diagnoses were treated as dummy variables (mood disorder vs psychotic disorders; psychotic disorders vs others; mood disorders vs others). Statistical analyses were performed using SPSS software 20.0 and R 3.4.0. RESULTS: Of the 236 measures of seclusion the mean age was 38.2 (±12.8), 196 (83%) patients were forcibly hospitalized prior to their seclusion, 147 (62%) had a diagnosis of psychotic disorder, 43 (18%) a diagnosis of mood disorder and 33 (14%) an "other diagnosis". Mean duration was 10.2 (1.5) days and median was 7.1 days. One hundred and thirty-five (47%) patients were in the group of duration ≥ 7 days. In bivariate analyses, variables associated with a duration ≥ 7 days were: being in forced hospitalization prior to the seclusion (P=0.04), administration of a sedative treatment (P=0.01) and against the group of others diagnoses the diagnosis of mood disorders (P<0.0005) and psychotic disorders (P=0.001). Multivariate analyses showed that, against the group of other diagnoses, the group of psychotic disorders [OR=3.3, CI 95% (1.3-8.4), P=0.01], the group of mood disorder [OR=2.7, CI 95% (1.4-4.9), P=0.002] and administration of sedative treatment [OR=8.1, CI 95% (2.0-32.5), P=0.003] were significantly associated with a duration ≥ 7 days. These results were independent from other confusion variables. Considering the hospitalization status, psychotic disorders was the only diagnosis which showed an association between duration ≥ 7 days and forced hospitalization [OR=2.9 CI 95% (1.1-7.8), P=0.03]. CONCLUSION: Our study highlighted two profiles of higher risk to remain ≥ 7days in seclusion. The first one is patients with a diagnosis of mood disorder who needed sedative treatment. The second one is patients with a diagnosis of psychotic disorder who needed sedative treatment and forced hospitalized before seclusion. Thus, these two profiles could be a good target to practice, in the first instance, measures to reduce seclusion duration in psychiatry settings.

Comparative effects of zopiclone and loprazolam on psychomotor and physical performance in active individuals.

OBJECTIVE: Sedative hypnotics are used by athletes to alleviate precompetition anxiety and insomnia. The effects of these agents on exercise tolerance have not been extensively researched. DESIGN: To determine the effects of sedative hypnotics on psychomotor and physical performance, a double-blind, placebo- (P) controlled, cross-over designed trial investigated the effects of zopiclone (Z) and loprazolam (L) on performance in 12 athletes. INTERVENTION: Subjects ingested either P, Z (7.5 mg), or L (2 mg) on three different occasions separated by a 1-week washout period. Eye-hand coordination tests, a 30-m sprint test, an agility test, and a graded treadmill run to exhaustion for determination of VO2max were performed 10 hours after drug administration. RESULTS: Subjects reported a significantly greater hangover effect following ingestion of L (8/11 subjects) compared with ingestion of Z (3/11 subjects; p < 0.01). A greater number of subjects felt alert after ingestion of P (9/11 subjects) and Z (9/11 subjects) compared with L (4/11 subjects; p < 0.01). The results of the eye-hand coordination tests, the 30-m sprint, the T-test, the VO2max, and the time to exhaustion during the treadmill run were not significantly altered following the ingestion of P, Z, and L. There was a significant difference between the delta values for Z and L for the number of missed responses in the eye-hand coordination tests (p < 0.02). Therefore, following the ingestion of L, subjects experienced a significant hangover effect and altered reaction time, whereas the ingestion of Z did not significantly impair either psychomotor or physical performance in the administered tests. CLINICAL RELEVANCE: Investigate the extent of the effects of sedative hypnotics on exercise performances, enabling team physicians to prescribe such drugs to the athlete more effectively.

No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET.

To investigate putative abnormalities of cortical 5-HT2A receptor density in schizophrenia, we used positron emission tomography and [18F]setoperone, a high-affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive schizophrenic patients and in 15 normal controls. No significant difference between the groups was observed in the whole or regional cortical binding potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor cortical density abnormalities in schizophrenics.

Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients.

OBJECTIVE: This study examined the binding to cortical serotonin 5-HT2A receptors of conventional doses of the typical neuroleptic chlorpromazine in comparison with clozapine, the prototype atypical antipsychotic, and amisulpride, a specific dopamine D2-D3 blocker. METHOD: Seventeen schizophrenic patients treated with chlorpromazine (75-700 mg/day), four treated with clozapine (200-600 mg/day), and five treated with amisulpride (200-1200 mg/day) were studied. Cortical 5-HT2A binding was estimated by reference to the values for 14 antipsychotic-free schizophrenic subjects with the use of positron emission tomography and [18F]setoperone, a high-affinity radioligand for cortical 5-HT2A receptors. RESULTS: A dose-dependent decrease in the number of available cortical binding sites for [18F] setoperone was demonstrated in the chlorpromazine group; for the highest dose, there was a virtual lack of sites available for binding. A very low percentage of available binding sites was also observed in the clozapine-treated patients at all doses. This suggests a high level of 5-HT2A blockade with both clozapine and high doses of chlorpromazine. No significant binding of amisulpride to 5-HT2A receptors was detected. CONCLUSIONS: A high level of 5-HT2A receptor blockade does not appear specific to clozapine in comparison with high doses of chlorpromazine, suggesting that the distinct clinical profiles of both drugs are unrelated to 5-HT2A blockade itself.

Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors.

To investigate adaptative changes of 5-HT2A receptors induced by SSRIs, six patients chronically treated for a depressive episode (four with fluoxetine, two with fluvoxamine) were studied with PET and [18F]setoperone. They were compared to eight untreated depressive patients. The mean frontal to cerebellum radioactivity concentration ratio, an index of the [18F]setoperone specific binding to 5-HT2A receptors, was higher in treated than in untreated patients, when age was taken into account. This suggests that chronic treatment by SSRIs could induce an up-regulation of the 5-HT2A receptors, and that 5-HT2A receptor down-regulation is not a common mechanism for the therapeutic effects of all serotoninergic antidepressive drugs.

The effect of fluoxetine on anxiety and depression symptoms in cancer patients.

Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients. A double-blind placebo-controlled study was therefore designed to assess the effectiveness of 20 mg fluoxetine. Of 115 cancer patients who fulfilled entry criteria for levels of distress, 45 patients were randomized to a fluoxetine treatment group (FA) and 46 patients to a placebo group (PA) after a 1-week placebo period designed to exclude placebo responders. The Montgomery and Asberg Depression Scale (MADRS), the Hamilton Anxiety Scale (HAS), the Hospital Anxiety and Depression Scale (HADS), the Revised Symptom Checklist (SCL90-R) and the Spitzer Quality of Life Index (SQOLI) were used to assess the efficacy of fluoxetine. The response rate, defined by a HADS score lower than 8 after 5 weeks of treatment, was not significantly higher in the FA group (11%) compared to the PA group (7%). Compared to the PA group, patients in the FA group showed a significantly greater decrease in SCL90-R mean total score after 5 weeks, but not a greater decrease in HADS mean score. No difference between the two groups was found in observer-reported assessments (MADRS, HAS and SQOLI). Significantly more drop-outs were observed in the FA group (n = 15) than in the PA group (n = 7), although the frequencies of side-effects were not significantly different.

Time course of prefrontal lobe dysfunction in severely depressed in-patients: a longitudinal neuropsychological study.

The Stroop Colour-Word Test (SCWT) and the Verbal Fluency Test (VFT), two tests that have been suggested to be particularly sensitive to prefrontal dysfunction, were administered to 23 severely depressed in-patients. Both tests were impaired in patients at inclusion, but only verbal fluency normalized with successful treatment of depression. VFT impairment is consistent with the hypothesis of a left prefrontal cortex dysfunction in depression. Moreover, the persistence of an impaired performance on SCWT in patients at discharge suggests that a selective attention deficit may persist in patients beyond a clear clinical improvement.

The identification of Mycoplasma mycoides mycoides LC as the aetiological agent of balanoposthitis and vulvovaginitis in sheep in South Africa.

Clinical ulcerative balanoposthitis and vulvovaginitis was experimentally reproduced in 14 sheep infected with a Mycoplasma mycoides mycoides LC field strain, isolated from the Straussheim Dorper stud. The study encompassed a series of field observations, a therapeutic trial and experimental investigations. A wide range of bacteria and various mycoplasma spp., but no viruses, were isolated from a large number of infected animals.

An outbreak of contagious bovine pleuropneumonia in the Owambo Mangetti area of South West Africa/Namibia: microbiological, immunofluorescent, pathological and serological findings.

An outbreak of contagious bovine pleuropneumonia (CBPP) in the Owambo Mangetti area of South West Africa/Namibia in 1982 led to the slaughter of 3,153 cattle. The lungs of 266 of these animals were scrutinized for gross lesions of CBPP and samples of lung tissue, sequestral contents or pleural fluid were submitted to the Veterinary Research Institute (VRI), Onderstepoort for microbiological, immunofluorescent and pathological examination. Immunofluorescence proved to be the most successful method of diagnosis producing 96% of positives, while mycoplasma isolations were only positive in 64% of the 55 specimens processed in parallel. This clearly demonstrated the value of the former technique in the accurate as well as rapid diagnosis of CBPP. The impression smear technique employed, using Eriochrome black counterstaining proved most satisfactory and easy to interpret. The isolation of M. mycoides was influenced by the transit times and temperature of the samples on arrival at the VRI. No pathogenic bacteria were found in routine aerobic bacterial cultures from 27 of the samples submitted. Complement fixing antibodies were present in the sera of 16 cattle and titres varied between 10 and 320. Animals in which antibodies were absent included those with early lung lesions and some with sequestra.

Mycoplasma mycoides recovered from the frontal sinus of an ox.

The isolation of M. mycoides from the frontal sinus of an ox is recorded. The possibility that this observation may reflect a true carrier state and be responsible for field outbreaks of obscure origin is considered.

Mycoplasmas recovered from bovine genitalia, aborted foetuses and placentas in the Republic of South Africa.

A total of 917 Mycoplasma isolations were made from 4 092 specimens originating from 2 874 cattle in private herds and at AI stations. The percentages of isolations from the different sources were: cervico-vaginal mucus 14,6%, semen 43%, preputial wash 25%, foetuses 3,3% and placentas 15%. Mycoplasma bovigenitalium, the most common isolate, was recovered from 39% of males, 47% of females, 25% of foetuses and 11% of placentas. A wide spectrum of mycoplasmas was present, and varying combinations were common. The possible pathogenic significance of the isolates is discussed.

Unilateral orchitis in a bull caused by Brucella abortus biotype1.

A case of Brucella orchitis in a Brahman bull is described. Positive serological titres were detected 1 month before clinical symptoms became obvious, whereas the seminal plasma only contained detectable levels of antibody after the onset of orchitis. It is concluded that serological assays on the seminal plasma alone are inadequate to detect sub-clinically infected animals, and consequently particularly bulls that are intended for use in AI centres should be subjected to a full battery of serological tests as well, before they are certified to be free of brucellosis. The pathology seen in this case was an acute, necrotic orchitis characterized by the presence of numerous granulomas containing the Brucella organisms centrally.