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The aging of population has dramatically broadened the total number of Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA) performed worldwide. To optimize the number of blood transfusions performed, a multimodal and multidisciplinary approach was introduced, called Patient Blood Management (PBM). The aim of the present retrospective study is to evaluate the feasibility and clinical outcomes of a PBM protocol applied in a national referral center for joint replacement surgery. Clinical reports of 9,635 patients undergoing primary THA or TKA, from 2014 to 2019, were screened. The trends of hemoglobin value at admission and at day 4 after surgery were analyzed. Furthermore, the trend of blood bags' requests and blood transfusions was longitudinally evaluated to assess the efficacy of our PBM protocol and its potential impact in reducing the length of stay in the hospital.In 2014, mean hemoglobin (Hb) levels at postoperative day 4 were 10.3 g/dl and 10.2 g/dl for TKA (unilateral and bilateral, respectively), and in 2019 were 11.3 g/dl and 11.6 g/dl (unilateral and bilateral, respectively, p=0.001). Total requested red blood cell (RBC) transfusions by each surgery over time have decreased for THA (277 in 2014 vs. 120 in 2019, p=0.001). A correlation matrix analysis between Hb level, body mass index (BMI), age, days spent in orthopedic (OR) ward and number of requested transfusions showed that RBC bags transfusions were related to the length of the hospital stay.A timely application of a PBM protocol in the perioperative period of TKA and THA was significantly associated to the reduction of blood transfusions and total length of hospital stay, with clear benefits for both the patients and the hospital.

Objective Although telehealth has become a central component of medical care in response to the coronavirus disease 2019 (COVID-19) pandemic, comprehensive pediatric neuropsychological assessment over virtual platforms lacks empirical efficacy. This paper presents: a) the results of a quality improvement project examining the feasibility of in-person evaluation in the context of safety measures that alter test standardization, b) the impact such changes had upon neuropsychological test scores, and c) how using a hybrid model of clinical service delivery affected access to care. Method We compared demographic and outcome variables between patients seen during the pandemic (N = 87) to a group of patients seen in our service immediately prior to COVID-19 (N = 87). A subset of those patients were case-matched for age and diagnosis (N = 39 per group). Children seen for neuropsychological re-evaluation during the pandemic (N = 10) were examined using pairwise comparison. Results Groups did not differ on age, sex, or FSIQ. Despite changes to standardized administration, no group differences were found for any selected neuropsychological test variables in the larger sample or subsamples. In fact, all variables were moderately to highly correlated in the re-evaluation subgroup. The hybrid model expedited feedback sessions and increased face-to-face (telehealth) feedbacks. Conclusions A hybrid model incorporating modified in-person testing and intake and feedback encounters via telehealth may be a feasible and effective way to provide pediatric neuropsychological services. These preliminary findings suggest such novel aspects of neuropsychological evaluation could represent an improvement over pre-COVID models, especially in rural settings.

The number of joint replacements is expected to dramatically increase, and the optimization of the available resources is fundamental to maintain high clinical standards while providing an efficient treatment to an increasing number of patients. The present study describes the outcomes of the application of a rapid recovery (RR) protocol in a referral center for hip and knee replacement surgery.The medical records of every patient undergoing primary hip or knee replacement in 2019 were identified and all the relevant data were retrospectively extracted and compared to those of year 2016 (the last year before the onset of the rapid recovery protocol). The following outcomes were considered: 1) length of stay (LOS); 2) total number of TKR and THR; 3) pre- and post-operative subjective questionnaires; 4) NRS for pain at day 1 following surgery; 5) mean hemoglobin value at discharge; 6) number of blood transfusion performed; 7) complications following surgery.The mean LOS was significantly lower for patients managed through the rapid recovery protocol: 5.1 ± 1.4 days vs. 10.4 ± 2.3 days (p0.0001). The earlier discharge of patients promoted an overall increase in the total number of joint replacement procedures performed (2,806 in year 2019 vs. 2,236 in year 2016; p0.0001). Higher hemoglobin values at discharge were found in the RR group (10.6 ± 1.4 g/dl vs. 9.6 ± 1.2 g/dl, p = 0.049). No difference was observed in terms of clinical scores and overall complication rate.The application of a multimodal RR protocol for THR and TKR patients was able to reduce the length of stay and optimize the use of blood products, without increasing the risk of complications or jeopardizing the functional recovery.

International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

OBJECTIVE: Children living with HIV can experience cognitive difficulties. Most neuropsychological tests have been constructed in Western languages, meaning they may not be appropriate for use in non-Western settings. To address this, we used an entirely nonverbal measure of cognitive ability in a sub-Saharan African sample. METHODS: For this cross-sectional analysis, 316 children (162 HIV+ and 154 HIV−, ages 3-8) completed the Leiter-3 as part of a larger study in Dar es Salaam, Tanzania. Statistical tests included analysis of covariance and multiple linear regression to account for environmental variables. RESULTS: HIV+ children performed worse than HIV− controls on two composite scores: Nonverbal IQ (p < .001) and Processing Speed (p < 0.001). Similar trends were observed on core subtests. Multiple linear regression models revealed that age, socioeconomic status, and school attendance predicted all Leiter-3 test composites. Critically, the addition of HIV status to the models improved prediction of Nonverbal IQ (ΔR(2) = 0.03, p = .001) and Processing Speed (ΔR(2) = 0.06, p < .001). CONCLUSIONS: Children living with HIV performed worse than HIV− controls on most Leiter-3 measures. While age, SES, and school attendance predicted Leiter-3 performance, HIV status improved prediction capabilities when added to the model. The Leiter-3 may offer a viable measure of cognitive ability in non-Western settings that can be used in its original form without translation.

Information on the amount of water held by woodchips in the field is needed to assess environmental risks when they are kept in stockpiles or for inferring their efficiency as denitrifying bioreactors. Reflectometry is a widely used method for estimating volumetric water content ( θ ) in permeable media, but material-specific calibration functions should be developed. This study aimed at developing relationships between the bulk dielectric permittivity ( e b ) and θ in woodchips considering their particle size distribution (PSD), temperature ( T ) and the dielectric permittivity of the dry material plus air ( e sa ). The e b of fine, medium and coarse PSDs were measured with CS616-L water content reflectometers up to θ of 0.83 cm3/cm3 and at T (°C) of 10°, 24°, 37°, 55° and 70°. Calibration equations were developed using a multivariate power law function fitted to the data with a hierarchical Bayesian inference procedure. The best fit ( R 2 = 0.96; RMSE =0.04 cm3/cm3) was obtained for the fine PSD ( e sa ∼ 1.09); while medium ( e sa ∼ 1.09) and coarse ( e sa ∼ 1.03) PSDs were more influenced by T and the presence of large air voids ( R 2 ∼ 0.92; RMSE ∼0.06 cm3/cm3). A modified calibration equation independent of PSD ( e sa = 1) reduced only slightly the goodness-of-fit ( R 2 = 0.90; RMSE =0.07 cm3/cm3). The equations developed in this study are well suited for field applications as they cover a wider range of θ than previously published functions and they are applicable within the range of T found in field applications.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.

International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.

Preoperative anaemia and non-anaemic iron deficiency are independent risk factors for perioperative blood transfusion, morbidity, and mortality. Although the efficacy to treat anaemia with iron infusion before elective surgery has been widely studied, the literature offers few data about the efficacy of treating iron deficient, non-anaemic patients before elective surgery. This retrospective study assessed the effect of preoperative ferric carboxymaltose (FC) administration on the concentration of Haemoglobin (Hb) in iron deficient, non-anaemic individuals following total knee or hip arthroplasty. A treatment group of 83 non-anaemic iron deficient individuals scheduled for arthroplasty were administered a 1000mg FC infusion over 15 minutes 4 weeks prior to surgery. In the control group (n=62) FC was not administered preoperatively. No individual from either group was given any iron supplement following the pre-operative visit. Blood tests were performed and analysed 4-weeks before surgery, on admission, and then 2-days, 4-days and 4-weeks postoperatively. Number of blood transfusions performed and adverse events were recorded. Hb concentration did not change substantially after iron supplementation prior to surgery. No difference in the number of blood transfusions was observed. In the treatment, group postoperative Hb concentration recovered significantly more quickly compared to control (p=0.0047). No adverse event was reported. The administration of FC in non-anaemic iron deficient individuals quickens the restoration of Hb concentration following THA or TKA procedures.

International audience; The aim of our study was to compare the performance of three different instruments measuring clinical and cognitive dimensions of insight. Data on 182 outpatients with schizophrenia and one-year follow-up assessments was drawn from the FACE-SZ cohort. Awareness of clinical state (« clinical insight ») was measured using both a clinician-rated measure (the Scale to assess Unawareness of Mental Disorder (SUMD)), and a self-report measure (the Birchwood Insight Scale (BIS). Cognitive insight was measured using a self-report measure (the Beck Cognitive Insight Scale (BCIS)). For each scale, change in insight was examined at the follow-up. Correlations between SUMD and BIS subscales measuring same dimensions were significant. BIS-BCIS correlations were weak for all combinations except between BIS illness dimension and BCIS composite score. At the follow-up, BIS and SUMD awareness of treatment need improved whereas illness and symptom awareness increased only on the SUMD. Conversely, cognitive insight composite scores decreased. Despite relatively good overall agreement between the two clinical insight instruments, considerable variability for similar insight dimensions measured by different instruments was found. Agreement between cognitive and clinical insight is moderate. Our study strengthens the argument that insight is harder to operationalize than other symptoms and may explain why it is so seldom explicitly targeted in schizophrenia treatment.

Although mortality by suicide in schizophrenia seems to have decreased in some countries over the last 30 years, it remains much higher than in the general population. Studies have shown this risk to impact around 5% of patients, corresponding to a risk almost 2.5 times higher than in the general population. Family psychoeducation in schizophrenia has been demonstrated to lead to symptom reductions and to an improvement of the quality of life, two factors that should contribute to decreasing the suicidal risk. Therefore, if families attend an efficient psychoeducation program, we can expect a decrease in the patient suicidal risk. Attending a family psychoeducation program at the beginning of the disease would also be associated with a stronger preventive effect on suicidal mortality. The objective of this study is to describe the suicide attempt rate of patients who suffer from schizophrenia before and one year after one of their relatives participated to the family psychoeducation program Profamille.We performed a retrospective study on 1209 people who attended the Profamille (V3.2 version) Family Psychoeducation Program. This program has 2 modules: an initial training module of 14 weekly or fortnightly sessions, and a consolidation module of 4 sessions over 2 years. Sessions last 4 hours and follow a precise and structured course. Data were collected from 40 different centers in France, Belgium and Switzerland and were based on participants assessed at the beginning and one year after the first module. Self-assessment from the relatives participating in the program provided the measure of patients' suicide attempts. An assessment at T0 explored the attempts over the 12 months before the beginning of the program while the assessment at T1 analyzed those during the 12 months following the end of the Program. The ChiThe number of participants reporting that their relative had attempted suicide in the previous 12 months decreased from 41 to 21. The annual attempts rate was evaluated at 6.4 % before the Profamille program and decreased to 2.4 % a year after the end of the program (P=0.0003). The reduction of the attempt rate was observed even for patients with schizophrenia for more than 10 years.This study shows the positive impact of Profamille on reducing the rate of suicide attempts in patients with schizophrenia. It has been shown that the risk is highest at the beginning of the disorder. Therefore, based on our results, it would seem appropriate to propose the Profamille program at an early stage.

International audience; Objectives The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. Methods More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. Results The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset < 19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. Conclusions In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.; Objectifs Le présent article propose de faire un retour sur les 10 ans d’expérience du réseau national des 10 centres experts schizophrénie Français, à travers une revue des principales publications scientifiques qui en sont issues. Méthodes À ce jour, les données de plus de 700 patients ont pu être analysées. Globalement, cette population est composée de trois quarts d’hommes, est âgée en moyenne de 32 ans, la durée moyenne de maladie est d’environ 11 ans, l’âge moyen de début de maladie est de 21 ans, la durée de psychose non traitée est d’environ un an et demi. 55 % des sujets sont consommateurs de tabac au moment de l’évaluation. Enfin, un focus sera fait sur les projets de recherche multicentriques collaboratifs déployés au sein de ce réseau. Résultats Les principales données obtenues peuvent être résumées comme suit : le syndrome métabolique reste deux fois plus fréquent dans la schizophrénie qu’en population générale et n’est pas correctement pris en charge ; des troubles cognitifs spécifiques ont été identifiés chez les patients consommateurs de benzodiazépines et chez les patients présentant une inflammation périphérique. Des spécificités liées au sexe ont également été observées ; la dépression comorbide reste très fréquente, elle est associée à une diminution de la qualité de vie et à une augmentation de la dépendance nicotinique chez les fumeurs. Prendre en charge la dépression et les symptômes négatifs pourraient fortement améliorer la qualité de vie des patients ; le délai à l’instauration du traitement est plus long pour les schizophrénies se déclenchant avant 19 ans et chez les consommateurs de cannabis. L’adhésion au traitement est diminuée chez les patients rapportant un ressenti subjectif négatif du traitement, indépendamment de la prise de poids ou d’un syndrome extrapyramidal. Enfin, l’akathisie est très fréquente et fortement associée à la polythérapie antipsychotique. Conclusions Ces résultats conduisent à formuler plusieurs recommandations. Le dépistage du trouble et le traitement devraient être renforcés chez les adolescents et les consommateurs de cannabis. Tous les patients devraient bénéficier d’une évaluation neuropsychologique au début de leur trouble, après stabilisation sous traitement, puis de façon plus espacée au cours de leur suivi. La prise en charge des paramètres métaboliques, de l’alimentation et de l’activité physique devrait être renforcée. La balance bénéfice/risque de la prescription de benzodiazépines doit être réévaluée régulièrement au regard de son impact notamment sur la cognition. La monothérapie antipsychotique est recommandée autant que possible pour limiter les effets indésirables. La dépression reste sous-diagnostiquée et doit faire l’objet d’une évaluation systématique et d’un traitement spécifique. La remédiation cognitive doit également être plus largement proposée chez les patients présentant des troubles cognitifs.

Introduction This study aimed was to investigate the relationship between different types of childhood trauma and the level of insight (i.e., awareness of having a psychiatric disorder) in subjects suffering from schizophrenia, as well as the putative role of clinical mediators. Methods 294 community-dwelling subjects with stable schizophrenia were included into FACE-SZ, a multicentre cross-sectional study. All patients were assessed by specialized multidisciplinary teams. The level of insight was assessed by the Scale to assess Unawareness of Mental Disorder (SUMD), and childhood trauma by the Childhood Trauma Questionnaire (CTQ). Path analyses from the five CTQ subscales (physical abuse and neglect, emotional abuse and neglect, and sexual abuse) and the SUMD, with current symptomatology (i.e., positive, negative, global psychopathology and depression) as mediator, was performed. Results Physical neglect (β = 0.14) and abuse (β = 0.13) were significantly associated with poor insight. Negative symptoms were a clinical mediator of the relationship between physical neglect and poor insight. Moreover, positive (β = 0.21) and negative (β = 0.30) symptoms were associated with poor insight, whereas depression (β = −0.14) was associated with higher levels of insight. Discussion For the first time, this study shows a significant relationship between childhood trauma, specifically physical neglect and abuse, and poor insight. The level of insight was linked to different clinical dimensions. Among subjects with schizophrenia, these results provide support for a role of childhood trauma in poorer management outcomes, and the need to provide treatment, including psycho-education that better targets the consequences of childhood trauma.

Leachate generation from open stockpiles of recycled woodchip materials is potentially harmful to aquatic ecosystems. There is growing interest in using numerical models to simulate leachate generation from outdoor piles, but this requires information about the hydraulic properties of the materials. The objectives of this study were to simulate leachate from woodchip piles with the numerical model HYDRUS-3D and to optimize subsets of parameters for single (SPM) and dual (DPM) pore flow models with the Bayesian Markov Chain Monte Carlo algorithm DREAMZS. Three experimental piles, each approximately 30 m3, were setup with mixtures of either once (coarse) or twice (fine) ground woodchips. Leachate continuously collected over a period of six months was similar across piles. As a result, subsets of optimized flow parameters for the coarse and fine woodchips were not different. Leachate predictions by the two pore flow models were similar and agreed reasonably with the field measurements, as indicated by Nash-Sutcliffe efficiency values greater than 0.6. This result suggests the simpler SPM is adequate for field predictions of leachate. However, leachate was consistently under-predicted by both pore models by 13–27% during rainfall events with more than 1 cm in 6 h. The optimized flow models can be used as a tool for studying pile management strategies.

The serotonin syndrome is a potentially deadly complication resulting from drug adverse effect, drug-drug interaction or overdose involving one or more serotonergic molecules, e.g., antidepressants, psychostimulants and sometimes an "ignored" serotonergic compound. The serotonin syndrome typically consists of a clinical triad including cognitive/behavioral, neurovegetative and neuromuscular features. However, this syndrome is characterized by major clinical heterogeneity, making the diagnosis difficult in practice. Moreover, many practitioners are quite unaware of this syndrome. Available scores and classifications can help physicians in their diagnosis approach. Knowing the responsible molecules, their potential interactions and mechanisms of action can help preventing this complication allowing therapeutic education among patients. This updated article reviews the clinical presentation, prevention, management, and pathophysiology of the serotonin syndrome, and addresses the most recent advances in pharmacogenetics regarding this syndrome.

Objectives Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). Method 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37 ± 9.86 years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as > 2 years. Results The mean DUP was 1.5 years. 80 participants (16.7%) had a DUP > 2 years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3 ± 6.67 years vs. 22.0 ± 6.51 years, adjusted odd ratio aOR = 0.91, 95%CI [0.86; 0.97], p = 0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR = 2.41, 95%CI [1.14–5.09], p = 0.02). Conclusion A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19 years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.

The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort.More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers.The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy.In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.

International audience; The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.

Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p 0.0001), current tobacco smoking (p 0.0001), clomipramine (p = 0.04), quetiapine (p 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.

Supplemental material, Supplemental_Material for Screening for cognitive deficits with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia scale by Paul Roux, Mathieu Urbach, Sandrine Fonteneau, Fabrice Berna, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, Julien Dubreucq, Catherine Faget-Agius, Guillaume Fond, Sylvain Leignier, Claire-Cécile Perier, Raphaëlle Richieri, Priscille Schneider, Franck Schürhoff, Anne Marie Tronche, Hanan Yazbek, Anna Zinetti-Bertschy, the FondaMental Advanced Centers of Expertise in Schizophrenia (FACE-SCZ) Collaborators, Christine Passerieux, Eric Brunet-Gouet, M Andrianarisoa, B Aouizerate, N Bazin, F Berna, O Blanc, L Brunel, E Bulzacka, D Capdevielle, I Chereau-Boudet, G Chesnoy-Servanin, JM Danion, T D’Amato, A Deloge, C Delorme, H Denizot, JM Dorey, C Dubertret, J Dubreucq, C Faget, C Fluttaz, G Fond, S Fonteneau, F Gabayet, E Giraud-Baro, D Lacelle, C Lançon, H Laouamri, M Leboyer, T Le Gloahec, Y Le Strat, PM Llorca, J Mallet, E Metairie, D Misdrahi, I Offerlin-Meyer, C Passerieux, P Peri, S Pires, C Portalier, L Ramet, R Rey, C Roman, A Schandrin, F Schürhoff, A Tessier, AM Tronche, M Urbach, F Vaillant, A Vehier, P Vidailhet, E Vilà, H Yazbek and A Zinetti-Bertschy in Clinical Rehabilitation

BACKGROUND: Google Trends (GT) searches trends of specific queries in Google, which potentially reflect the real-life epidemiology of allergic rhinitis. We compared GT terms related to ragweed pollen allergy in American and European Union countries with a known ragweed pollen season. Our aim was to assess seasonality and the terms needed to perform the GT searches and to compare these during the spring and summer pollen seasons. METHODS: We examined GT queries from January 1, 2011, to January 4, 2017. We included 15 countries with a known ragweed pollen season and used the standard 5-year GT graphs. We used the GT translation for all countries and the untranslated native terms for each country. RESULTS: The results of "pollen, " "ragweed, " and "allergy" searches differed between countries, but "ragweed" was clearly identified in 12 of the 15 countries. There was considerable heterogeneity of findings when the GT translation was used. For Croatia, Hungary, Romania, Serbia, and Slovenia, the GT translation was inappropriate. The country patterns of "pollen, " "hay fever, " and "allergy" differed in 8 of the 11 countries with identified "ragweed" queries during the spring and the summer, indicating that the perception of tree and grass pollen allergy differs from that of ragweed pollen. CONCLUSIONS: To investigate ragweed pollen allergy using GT, the term "ragweed" as a plant is required and the translation of "ragweed" in the native language needed.

Objective Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. Methods A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T . gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood level ≥ 3 mg/L. Results Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aOR = 1.1 [1.1–1.1], p = 0.04) and excitement subscores (aOR = 1.3 [1.1–1.6], p = 0.01), with two specific symptoms (i.e., reference delusion (aOR = 3.6 [1.2–10.6] p = 0.01) and alogia (aOR = 16.7 [2.0–134.7], p = 0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aOR = 3.8 [1.4–10.3], p = 0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all p > 0.05). TATA were associated with lower depressive symptoms (aOR = 0.8[0.7–0.9], p = 0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aOR = 3.5 [1.5–7.9], p = 0.003) but not with higher cognitive scores (p > 0.05). Conclusion The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.

Background Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. Methods Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. Results 53.7% were smokers. Mean age at tobacco onset was 17.2 years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR = 1.06 95%IC[1.02–1.12], for positive symptoms, OR = 1.1, 95%IC[1.02–1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR = 0.87, 95%IC [0.79, 0.95], OR = 0.95, 95%IC[0.91–0.98], OR = 0.41, 95%IC[0.22–0.76], OR = 0.56, 95%IC = [0.32, 0.99] and OR = 0.49, 95%IC [0.26–0.91]). Conclusion The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

International audience; OBJECTIVES:Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia.METHOD:A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales.RESULTS:Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p

Objectives Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. Method 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5 ± 12.1 and 31.6 ± 8.7 years, respectively) were tested with a comprehensive battery of neuropsychological tests. Results Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. Conclusion Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. Limits Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

Nowadays, silver nanoparticles (AgNPs) are utilized in numerous applications, raising justified concerns about their release into the environment. This study demonstrates the potential to use freshwater crayfish as a benthic-zone indicator of nanosilver and ionic silver pollution. Crayfish were acclimated to 20 L aquaria filled with Hudson River water (HRW) and exposed for 14 days to widely used Creighton AgNPs and Ag(+) at doses of up to 360 μg L(-1) to surpass regulated water concentrations. The uptake and distribution of Ag in over 650 exoskeletons, gills, hepatopancreas and muscles samples were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) in conjunction with two complementary U.S. EPA-endorsed methods: the external calibration and the standard additions. Reflecting the environmental plasticity of the two investigated species, Orconectes virilis accumulated in a dose-dependent manner more Ag than Procambarus clarkii (on average 31% more Ag). Both species showed DNA damage and severe histological changes in the presence of Ag. However, Ag(+) generally led to higher Ag accumulations (28%) and was more toxic. By the harvest day, about 14 ± 9% of the 360 μg L(-1) of AgNP exposure in the HRW oxidized to Ag(+) and may have contributed to the observed toxicities and bioaccumulations. The hepatopancreas (1.5-17.4 μg of Ag g(-1) of tissue) was identified as the best tissue-indicator of AgNP pollution, while the gills (4.5-22.0 μg g(-1)) and hepatopancreas (2.5-16.7 μg g(-1)) complementarily monitored the presence of Ag(+).

International audience; The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Objective Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. Method 240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L. Results MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. Conclusions The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

SUMMARYPrey assessing risk may miss cues and fail to defend themselves, or respond unnecessarily to false alarms. Error rates can be ameliorated with more information, but sampling predator cues entails risk. Red-eyed treefrogs have arboreal eggs and aquatic tadpoles. The embryos use vibrations in snake attacks to cue behaviorally mediated premature hatching, and escape, but vibrations from benign sources rarely induce hatching. Missed cues and false alarms are costly; embryos that fail to hatch are eaten and hatching prematurely increases predation by aquatic predators. Embryos use vibration duration and spacing to inform their hatching decision. This information accrues with cycles of vibration, while risk accrues over time as snakes feed. We used vibration playback experiments to test if embryos adjust sampling of information based on its cost, and measured latency to initiate hatching in videotaped snake attacks. Embryos did not initiate hatching immediately in attacks or playbacks, and the delay varied with the rate at which information accrued. Embryos started hatching sooner in response to stimuli with shorter cycles but sampled fewer cycles (less information) of longer-cycle stimuli before hatching. This flexible sampling is consistent with embryos balancing a trade-off between the value and cost of information.

The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus).The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80-100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70-75) is most common, mild intellectual disability (IQ: 55-75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses.General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40-50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30-40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms.Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life.

Background: Preeclampsia (PE) is a disorder that occurs in at least 5% of pregnancies and affects both the mother and the unborn baby. A dramatic increase of maternal serum inhibin A concentration in the second and third trimester of pregnancy is a common feature of PE and inhibin A measurement may add significant prognostic information for predicting PE in pregnant women. Design: We evaluated the presence and prevalence of gene polymorphisms for inhibin a subunit (INHα) in patients affected by PE (no.=50; study group), and in the general population (control group composed of 103 women and 42 men). Methods: DNA extraction, single strand conformation polymorphism analysis, DNA sequencing, restriction fragment length polymorphism analysis, and Fisher’s exact test were used. Results: A 769G→A transition was found in INHα1, but not in INHα2 or INHα3 fragment. This variant was found in 10/145 normal controls (7,6%), and in 1/50 preeclamptic patients (2%), without significant difference between the two groups (p=0.29). Conclusions: The prevalence of INHα gene variants is not increased in PE. Due to its frequency, the 769G→A transition may be considered a polymorphism present in the general Italian population.

A 45-year-old man presented with subacute onset of ataxia, diplopia, urinary retention and paraparesis. MR scan of brain showed abnormal T2 hyperintense signal within the cervical cord, medulla and lower pons and vascular appearances suggesting an arterio-venous fistula. The fistula was surgically explored and successfully disconnected with good clinical outcome. Brainstem or cervical dural arterio-venous fistulae more typically present as a myelopathy; only a handful of cases have presented with brainstem dysfunction. This is a rare but reversible cause of subacute brainstem dysfunction.

Patients with schizophrenia rarely develop rheumatoid arthritis, an autoimmune disease that exhibits genetic association with the HLA DRB1*04 gene. We previously investigated the hypothesis that schizophrenia is negatively associated with DRB1*04, and found that only half the expected number of schizophrenic patients had this gene when compared with controls. We now report the results of DRB1*04 genotyping in pedigrees multiply affected with schizophrenia. Polymerase chain reaction amplification and sequence-specific oligonucleotide probes were used to determine the DRB1 genotypes of the 187 members of 23 pedigrees multiply affected with RDC schizophrenia. DQA1, DQB1 and DPB1 genotypes were similarly determined. We analysed data using the extended transmission/disequilibrium test and found a trend for the preferential non-transmission of DRB1*04 alleles from heterozygous parents to their schizophrenic offspring (16 of 23 alleles not transmitted, chi 2 = 3.5, p = 0.06). We found no evidence for a gene of major effect using GENEHUNTER for parametric and non-parametric linkage analysis. The results from this small sample need to be interpreted with caution, but they are in keeping with previous reports and suggest that HLA DRB1*04 alleles may be associated with a reduced risk of schizophrenia.

ResumenLos estudios de tomografía computerizada (TC) han demostrado que el tamaño de los ventrículos laterales medido por la proporción ventrículo-cerebro (PVC), así como la anchura del tercer ventrículo, son estadísticamente mayores en los pacientes esquizofrénicos. Además, estas anomalías cerebrales difieren según los síntomas valorados con una escala de síntomas positivos y negativos. El propósito de este estudio era investigar, utilizando exploraciones de TC, a hermanos sanos de pacientes esquizofrénicos y relacionar los resultados con sus hermanos enfermos. Diecinueve hermanos sanos de 12 esquizofrénicos que habían sido estudiados con anterioridad sufrieron exploraciones de TC, que se compararon con las de su hermano esquizofrénico y con 17 sujetos de control no relacionados. Los resultados mostraron que, en 10 de las 12 familias, los esquizofrénicos tienen ventrículos (laterales y tercero) más grandes que sus hermanos sanos. La dilatatión ventricular de los hermanos sanos estaba correlacionada con la gravedad de los síntomas negativos de su hermano enfermo. Se debaten las implicaciones de una contributión familiar al tamaño ventricular y los síntomas negativos.

ResumenEn un estudio controlado doblemente ciego, la estimulación magnética transcraneal repetitiva (EMTr) provoca un efecto antidepresivo similar a la EMTr simulada en combinación con paroxetina. Ambos grupos tuvieron el mismo intervalo hasta la mejoría de las puntuaciones de la escala. La EMTr no parece ser eficaz como tratamiento auxiliar a la medicación farmacológica en la depresión mayor no resistente al tratamiento.

Because of an association between sexual aneuploidies and schizophrenia, and because schizophrenic siblings have been found to be more often of the same than of the opposite sex, the susceptibility locus for schizophrenia is thought to lie within the pseudoautosomal region of the sex chromosomes. We analysed 33 sibships comprising 18 pairs, 13 trios, and 2 quartets of affected siblings, and found support for non-random segregation of alleles at the DXYS14 locus in affected siblings. These findings are consistent with the pseudoautosomal hypothesis for schizophrenia and favour a genetic linkage between DXYS 14 and the disease.

In 1985, Barker et al. showed that it was possible to stimulate both nerves and brain using external magnetic stimulation without significant pain. During the past 10 years, therapeutic effects of repeated Transcranial Magnetic Stimulation (rTMS) have been widely studied in psychiatry and its efficacy has been demonstrated in the treatment of major depressive disorders, particularly as an alternative to electroconvulsivotherapy (ECT). Facing the large range of studies, we found necessary to propose an up-to-date review in French of the methodological and therapeutic variations among them.Based on an exhaustive consultation of Medline data and the Avery-George-Holtzheimer Database of rTMS Depression-Studies, supplemented by a manual research, only works evaluating the therapeutic efficacy of rTMS on depressive symptoms were retained, excluding all studies exclusively investigating the stimulation parameters or the tolerance as well as case reports.Out the 66 available reports we retained 30 studies. After a description of the main results of these 30 studies, several elements of the 66 will be discussed. Open studies demonstrated that short courses rTMS (5 to 10 sessions) produced a decrease in the mean Hamilton Depression Ratting Scale (HDRS) scores, although significant remission of depression in individuals was rare. Most authors had used high frequency rTMS applied to the left Dorso Lateral Prefrontal Cortex (left DLPFC). However, low frequency rTMS applied to the right DLPFC was also followed by significant reduction of HDRS scores. Parallel arm, double blind versus placebo studies are designed to clarify the therapeutic efficacy of rTMS therapy but conclude in contradicting results. Literature data globally confirms a greater efficacy of rTMS compared to placebo (37% responders in the active group vs 20% in the sham). This efficacy could in fact be even greater because the sham procedure is disputable in most studies. Indeed, positioning rTMS coil at 45 or 90 from the scalp may not represent an accurate sham procedure and the use of real sham coil is to be recommended. Only one study has suggested that associating rTMS and ECT could decrease the number of general anesthesia required. Therapeutic efficacy has been shown by either inhibiting the right DLPFC or by stimulating the left DLPFC, although some patients exhibit paradoxical responses. High frequency rTMS (5 Hz) increases cortical excitability and metabolism, while low-frequency rTMS stimulation ( 1 Hz) has the opposite effect. Other parameters are: relevant: intensity (from 80 to 110% of motor threshold), total number of stimulations (from 120 to 2 000) and total number of rTMS sessions (from 5 to 20). As suggested in most recent studies, higher-intensity pulses, higher number of stimulation or longer treatment courses may be more effective. Greater responsiveness to rTMS may be predicted by several patients' factors, including the absence of psychosis, younger age and previous response to rTMS therapy.Conclusions on these factors and others, such as the importance of anatomically accurate coil placement and the distance from the coil to the brain, await further investigation. Despite heterogeneity of these reports according to methodology and treatment parameters, the antidepressive properties of rTMS now appear obvious, opening interesting prospects, in particular in the treatment of pharmacoresistant major depressive patients and, we hope, administered as adjuvant therapy in non-resistant depression.Thus, many questions remain unanswered concerning the optimal stimulation parameters, privileged indications and maintenance sessions. This justifies the development of structured evaluation trials on larger samples.

Impulsive traits are key characteristics in a lot of psychiatric disorders and are part of the "normal" behaviour spectrum. Although impulsivity is a controversial concept, some questionnaires have focused on its "dysfunctional" aspect. The Barratt Impulsive Scale (BIS-10) is the scale the most used to explore impulsiveness, but it does not explore antisocial or nonconform behaviour. The Chapman Impulsive and Nonconformity Scale (INCS) is a questionnaire of 51 items that measures the impulsivity and nonconformism. The INCS reflects "failure to internalize societal norms, lack of empathy for the pain of others, and an unrestrained yielding to impulse and self-gratification" and was originally designed to assess psychosis proneness. It has been validated in the USA, but has not yet been validated in France. Interestingly, although it was not predictive of psychosis, high scorers on INCS exceeded controls on depression, and on rates of substance abuse. Furthermore, participants scoring high on hypomanic personality scale and INCS were found to have an especially heightened risk for bipolar disorders.To translate and determine reliability and validity of the French version of the Chapman Impulsive and Nonconformity Scale in young adults by comparison with the BIS.Chapman Impulsive and Nonconformity Scale has been back-translated into French, and filled out by 237 students (males: 104; females: 133; mean age: 20.4 [range 19-25]). BIS-10 was used for convergent validity. Each participant completed the two scales. Reliability and validity of the French form of INCS were assessed with the internal consistency (coefficient alpha of Cronbach and the split half reliability) and the convergent validity.In the French version of the INCS, the 51 items have high internal reliability (Cronbach's alpha=0.81 and split half reliability=0.80). Concerning the BIS, internal reliability is good (Cronbach's alpha=0.72 and split half reliability=0.66). Moreover, Pearson's r of the INCS/BIS is statistically significant (0.65) and underlines the concomitant validity of the INCS with the BIS.The psychometric properties of the French version of the INCS are very similar to those of the English version. Hence, the INCS could provide a way to explore the two related dimensions: impulsivity and nonconformism.

Despite recent developments, the impact of pharmacotherapy on social autonomy and interpersonal problem solving skills in patients with schizophrenia remains limited, with consequences in terms of socio-professional functioning. Indeed, independently of the positive, negative and/or disorganization symptoms, functional deficits in patients with schizophrenia rely mainly on various cognitive impairments.To determine the impact of a new Cognitive Remediation Strategy on interpersonal problem solving skills, social autonomy and symptoms in patients with schizophrenia.Thirty patients with schizophrenia were enrolled in a program consisting of 14 training sessions of 4 cognitive functions (attention/concentration, topological memory, logical reasoning, executive functions) using the REHACOM software. Measurements of attention (Continuous Performance Test, CPT), memory (Rivermead Behavioural Memory Test, RBMT) and executive functions (Wisconsin Card Sorting Test, WCST) as well as interpersonal problem solving skills (Assessment of Interpersonal Problem-Solving Skills, AIPSS) and social autonomy (Social Autonomy Scale, EAS) and finally schizophrenia symptoms (Positive And Negative Syndrom Scale, PANSS) were undertaken at the beginning and the end of the 14 remediation meetings.Cognitive functions, interpersonal problems solving skills, social autonomy and symptoms were significantly improved by the Cognitive Remediation Strategy.Our results confirm the therapeutic impact of a Cognitive Remediation Strategy among 30 schizophrenic patients stabilised on clinical, therapeutic and functional levels. The question of the long-term maintenance of such improvements still requires further investigation.

A healthy 9 year old girl presented with severe posterior knee pain and a small segmental non-occlusive popliteal venous thrombosis. The case is relevant for its unique presentation and symptoms. Lack of recanalisation persisted at one year follow up.