Psychothérapie en réalité virtuelle pour traiter les hallucinations auditives réfractaires de la schizophrénie : un essai clinique pilote

La schizophrénie est un trouble psychiatrique sévère et chronique qui pose des défis considérables. Alors que de nombreuses interventions pharmacologiques et psychosociales sont disponibles, un patient sur trois demeure résistant aux traitements et souffre de symptômes psychotiques persistants, notamment des hallucinations auditives verbales (AVH) pouvant être extrêmement invalidantes. Récemment, la thérapie Avatar a montré un large effet thérapeutique sur la sévérité des hallucinations auditives verbales (d = 0,8) en permettant aux patients d’engager un dialogue avec une représentation informatisée de leur(s) voix (Craig et al., 2017). Ces résultats très prometteurs ont été étendus par notre équipe lors d’une thérapie assistée par réalité virtuelle immersive (VRT). La présente étude consiste en un essai clinique de phase II, randomisé, contrôlé et suivant un devis partiellement croisé de 7 semaines. Dix- neuf patients atteints de schizophrénie et souffrant AVH réfractaires ont été recrutés pour suivre aléatoirement, soit la thérapie assistée par réalité virtuelle, soit leur traitement habituel (TAU). Le traitement habituel des patients consistait en la prise d’antipsychotique et des rencontres habituelles avec leur équipe traitante. Après 7 semaines, le groupe TAU recevait également la VRT. Une évaluation clinique avait lieu avant et après la VRT ou le TAU, puis 3 mois ensuite. L’évolution des symptômes a été analysée grâce à un modèle linéaire à effets mixtes. Nos résultats ont montré que la VRT produit une amélioration significative de la sévérité des AVH et particulièrement la détresse associée (d=1,2), des symptômes dépressifs et de la qualité de vie se maintenant jusqu’à 3 mois. La VRT est une intervention novatrice très prometteuse dans le traitement des AVH réfractaires de la schizophrénie.Schizophrenia is a chronic and severe psychiatric disorder that poses significant challenges. While many pharmacological and psychosocial interventions are available, many treatment- resistant schizophrenia patients continue to suffer from persistent psychotic symptoms, notably auditory verbal hallucinations (AVH), which are highly disabling. This unmet clinical need requires new innovative treatment options. Recently, a psychological therapy using computerized technology has shown large therapeutic effects on AVH severity (d=0.8) by enabling patients to engage in a dialogue with a computerized representation of their voices (Craig et al., 2017). These very promising results have been extended by our team using immersive virtual reality (VR). Our study was a 7-week phase-II, randomized, controlled, partial cross-over trial. Nineteen schizophrenia patients with refractory AVH were recruited and randomly allocated to either VR-assisted therapy (VRT) or treatment-as-usual (TAU). The group allocated to TAU consisted of antipsychotic treatment and usual meetings with clinicians. The TAU group then received a delayed 7 weeks of VRT. A follow-up was ensured 3 months after the last VRT therapy session. Changes in psychiatric symptoms, before and after TAU or VRT, were assessed using a linear mixed-effects model. Our findings showed that VRT produced significant improvements in AVH severity, particularly associated distress (d=1.2), depressive symptoms and quality of life that lasted at the 3-month follow-up period. VRT is a highly novel and promising intervention for refractory AVH in schizophrenia

General principles of preclinical study design.

Preclinical studies using animals to study the potential of a therapeutic drug or strategy are important steps before translation to clinical trials. However, evidence has shown that poor quality in the design and conduct of these studies has not only impeded clinical translation but also led to significant waste of valuable research resources. It is clear that experimental biases are related to the poor quality seen with preclinical studies. In this chapter, we will focus on hypothesis testing type of preclinical studies and explain general concepts and principles in relation to the design of in vivo experiments, provide definitions of experimental biases and how to avoid them, and discuss major sources contributing to experimental biases and how to mitigate these sources. We will also explore the differences between confirmatory and exploratory studies, and discuss available guidelines on preclinical studies and how to use them. This chapter, together with relevant information in other chapters in the handbook, provides a powerful tool to enhance scientific rigour for preclinical studies without restricting creativity

The Psychometric Properties of a Short UPPS-P Impulsive Behavior Scale Among Psychiatric Patients Evaluated in an Emergency Setting

Objective: Impulsivity is a multidimensional construct that has an important role for the understanding of diverse psychopathologies and problematic behaviors. The UPPS-P impulsive behavior scale, measuring five distinct facets of impulsivity, has been subject to several studies. No study has investigated the clinical utility of this questionnaire amongst an unstable psychiatric population. The aim of the current study is to examine the psychometric properties of the short version of this scale in a psychiatric emergency unit.Method: The S-UPPS-P was administered to 1,097 psychiatric patients in an emergency setting, where a subgroup of 148 participants completed a follow-up. The internal consistency, the construct validity, the test-retest reliability, and correlations with a substance misuse measure were examined.Results: Confirmatory factor analyses supported a five-factor solution. Results indicated good psychometric properties across psychiatric diagnoses and gender. The S-UPPS-P was partially invariant across sexes. The authors have found differences on the loading of one item and on the thresholds of two items from lack of premeditation and positive urgency subscales.Conclusion: This validation study showed that the UPPS-P conserved good psychometric properties in an unstable psychiatric sample, indicating that the instrument can be utilized in such settings

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret.

Background: Rodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research, would identify the emetic potential of the GLP-1R agonist, exendin-4, and any associated effects on gastric motor function, appetite and cardiovascular homeostasis. Methods: The biological activity of the GLP-1R ligands was investigated in vivo using a glucose tolerance test in pentobarbitone-anesthetised ferrets and in vitro using organ bath studies. Radiotelemetry was used to investigate the effect of exendin-4 on gastric myoelectric activity (GMA) and cardiovascular function in conscious ferrets; behaviour was also simultaneously assessed. Western blot was used to characterize GLP-1R distribution in the gastrointestinal and brain tissues. Results: In anesthetised ferrets, exendin-4 (30 nmol/kg, s.c.) reduced experimentally elevated blood glucose levels by 36.3%, whereas the GLP-1R antagonist, exendin (9–39) (300 nmol/kg, s.c.) antagonised the effect and increased AUC0–120 by 31.0% when injected alone (P < 0.05). In animals with radiotelemetry devices, exendin-4 (100 nmol/kg, s.c.) induced emesis in 1/9 ferrets, but inhibited food intake and decreased heart rate variability (HRV) in all animals (P < 0.05). In the animals not exhibiting emesis, there was no effect on GMA, mean arterial blood pressure, heart rate, or core body temperature. In the ferret exhibiting emesis, there was a shift in the GMA towards bradygastria with a decrease in power, and a concomitant decrease in HRV. Western blot revealed GLP-1R throughout the gastrointestinal tract but exendin-4 (up to 300 nM) and exendin (9–39), failed to contract or relax isolated ferret gut tissues. GLP-1R were found in all major brain regions and the levels were comparable those in the vagus nerve. Conclusions: Peripherally administered exendin-4 reduced blood glucose and inhibited feeding with a low emetic potential similar to that in humans (11% vs 12.8%). A disrupted GMA only occurred in the animal exhibiting emesis raising the possibility that disruption of the GMA may influence the probability of emesis occurring in response to treatment with GLP-1R agonists

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

Enhanced He-alpha emission from "smoked" Ti targets irradiated with 400nm, 45 fs laser pulses

We present a study of He-like 1s(2)-1s2p line emission from solid and low-density Ti targets under similar or equal to 45 fs laser pulse irradiation with a frequency doubled Ti: Sapphire laser. By varying the beam spot, the intensity on target was varied from 10(15) W/cm(2) to 10(19) W/cm(2). At best focus, low density "smoked" Ti targets yield similar to 20 times more He-alpha than the foil targets when irradiated at an angle of 45 degrees with s-polarized pulses. The duration of He-alpha emission from smoked targets, measured with a fast streak camera, was similar to that from Ti foils