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Resume Introduction Le devoilement de soi par les professionnels de la sante est une pratique courante, bien que controversee quant au moment opportun, a l’etendue et au contenu des informations partagees et aux consequences cliniques. Objectif Cette etude qualitative vise a enqueter sur de devoilement de soi chez les professionnels de la sante et du monde socioeducatif. Methode Treize entretiens approfondis avec les animateurs d’une intervention pour ameliorer le plaisir et la motivation dans la schizophrenie. Les entretiens ont fait l’objet d’une analyse thematique. Resultats Les professionnels decrivent leurs devoilements comme un partage authentique d’experiences vecues. Du point de vue du contenu, les professionnels selectionnent des evenements simples de leur vie personnelle ou professionnelle, qu’ils trouvent faciles a partager avec les patients, en groupe. Les criteres de selection de ces experiences concernent principalement la valeur therapeutique et sont formules en termes de pertinence du contenu et de l’utilite envisagee pour le patient ainsi que d’authenticite. La revelation de soi genere une redefinition des places dans l’interaction conduisant a une relation plus egalitaire. Conclusions Le devoilement de soi s’avere etre un outil pour developper et maintenir la relation therapeutique. De plus amples etudes sur le phenomene seraient utiles pour concevoir la formation des professionnels.

Resume Objectifs Le but de cette etude pilote etait de tester la faisabilite et l’acceptabilite de la version francaise d’un programme anime par des pairs sur le devoilement a autrui d’informations sur sa maladie pour des personnes atteintes de troubles psychiatriques. Materiel et methode Honnete, ouvert, pret (HOP) est un programme court qui invite les participants a echanger sur la problematique du devoilement de la maladie psychique. Trente et une personnes souffrant de troubles psychiatriques ont ete recrutees dans trois institutions psychosociales pour tester ce programme. Resultats Les resultats montrent que le programme est faisable et acceptable pour les participants. La participation aux sessions pourrait conduire a une reduction de l’auto-stigmatisation. Conclusions Le programme HOP offre une opportunite aux personnes atteintes de troubles psychiques d’echanger et de reflechir sur le dilemme du devoilement de la maladie psychique.

Introduction: The Asia-Pacific region has the highest number of active smokers in the world. Efforts to reduce tobacco use should implement evidence-based measures. The Association of Pacific Rim U...

The epigenetic modifier histone deacetylase-2 (HDAC2) is frequently dysregulated in colon cancer cells. Microsatellite instability (MSI), an unfaithful replication of DNA at nucleotide repeats, occurs in about 15% of human colon tumors. MSI promotes a genetic frameshift and consequently a loss of HDAC2 in up to 43% of these tumors. We show that long-term and short-term cultures of colorectal cancers with MSI contain subpopulations of cells lacking HDAC2. These can be isolated as single cell-derived, proliferating populations. Xenografted patient-derived colon cancer tissues with MSI also show variable patterns of HDAC2 expression in mice. HDAC2-positive and HDAC2-negative RKO cells respond similarly to pharmacological inhibitors of the class I HDACs HDAC1/HDAC2/HDAC3. In contrast to this similarity, HDAC2-negative and HDAC2-positive RKO cells undergo differential cell cycle arrest and apoptosis induction in response to the frequently used chemotherapeutic 5-fluorouracil, which becomes incorporated into and damages RNA and DNA. 5-fluorouracil causes an enrichment of HDAC2-negative RKO cells in vitro and in a subset of primary colorectal tumors in mice. 5-fluorouracil induces the phosphorylation of KAP1, a target of the checkpoint kinase ataxia-telangiectasia mutated (ATM), stronger in HDAC2-negative cells than in their HDAC2-positive counterparts. Pharmacological inhibition of ATM sensitizes RKO cells to cytotoxic effects of 5-fluorouracil. These findings demonstrate that HDAC2 and ATM modulate the responses of colorectal cancer cells towards 5-FU. Graphical abstract

BackgroundThe dissemination of new interventions in clinical practice remains challenging. E-learning may provide wide access in various settings and allow tailored learning trajectories and an adapted training pace. This study evaluates an online platform to train professionals to lead the Positive Emotion Program for Schizophrenia (PEPS) for patients with anhedonia. This study aims to test the reception provided by clinicians to the platform and its perceived usefulness and investigate whether e-PEPS training improves knowledge about the facilitation of PEPS.Materials and MethodsParticipants were recruited through advertisements. All participants provided their informed consent on a registration form and completed two pre-test questionnaires, a knowledge test on negative symptoms in schizophrenia, learning strategies and the partnership relationship, and a test on the ability to savor pleasant moments. After the training, they completed the same questionnaire and an evaluation form of the training and its application in personal and professional life.ResultsTwo-hundred and ten participants were registered to participate into the study, 185 received the access to the platform, and 101 participants completed the training and the post-test assessments. Satisfaction with training was high. The results showed that the participants significantly improved their knowledge about PEPS and increased the skills taught in their personal repertoire after the training. The training allows most clinicians to plan to lead a PEPS group in the year following training.DiscussionAs a result of this study, training has been improved and is now freely available to all interested clinicians.

Harmful consequences of self-stigma in schizophrenia are well established in the literature, but its relationship with symptomatology remains unclear. Self-stigma describes the process by which some patients eventually accept, adhere to and apply to themselves the stereotypes associated with schizophrenia. This study aims to describe self-stigma experienced by people with schizophrenia in French-speaking Switzerland and to examine the relationship between self-stigma and depression. This was a longitudinal study including 80 participants. Correlation and regression analyses were used to examine the relationship between self-stigma and depression over three points of time. Correlations between Stigma Scale subdimensions and sociodemographic variables indicated that age and duration of illness were associated with the discrimination subscale. Self-stigma was strongly correlated with depression over time, whereby higher scores of self-stigma were associated with higher depression. More precisely, the more the patient felt discriminated against and the less he or she perceived the positive aspects of his or her illness, the greater the symptoms of depression. This study highlights the severity of self-stigma endorsed by people with schizophrenia in French-speaking Switzerland. The results provide new knowledge about self-stigma and its potential impact on depressive symptoms. Implementation of self-stigma assessment in clinical practice will allow distinctions to be made between the impact of self-stigma and the consequences of schizophrenia to recommend appropriate intervention.

Senescence is an important consequence of cytostatic drug-based tumor therapy. Here we analyzed to which degree the anticancer drug oxaliplatin induces cell death, cell cycle arrest, and senescence in colorectal cancer (CRC) cells and elucidated the role of p53. Oxaliplatin treatment resulted in the G2-phase arrest in all CRC lines tested (HCT116p53+/+, HCT116p53−/−, LoVo, SW48 and SW480). Immunoblot analysis showed that within the p53-competent lines p53 and p21CIP1 are activated at early times upon oxaliplatin treatment. However, at later times, only LoVo cells showed sustained activation of the p53/p21CIP1 pathway, accompanied by a strong induction of senescence as measured by senescence-associated β-Gal staining and induction of senescence-associated secretory phenotype (SASP) factors. Opposite to LoVo, the p53/p21CIP1 response and senescence induction was much weaker in the p53-proficient SW48 and SW480 cells, which was due to deficiency for p14ARF. Thus, among lines studied only LoVo express p14ARF protein and siRNA-mediated knockdown of p14ARF significantly reduced sustained p53/p21CIP1 activation and senescence. Vice versa, ectopic p14ARF expression enhanced oxaliplatin-induced senescence in SW48 and SW480 cells. Our data show that oxaliplatin-induced senescence in CRC cells is dependent on p53 proficiency, however, a significant induction can only be observed upon p14ARF-mediated p53 stabilization.

Background According to practice guidelines, patients with clinical stage T1–2 node-negative small-cell lung cancer are candidates for surgical resection. However, the role of pneumonectomy in small-cell lung cancer patients is not well understood. The objective of this study was to assess the extent to which pneumonectomy is used and to evaluate the survival implications for small-cell lung cancer patients who underwent pneumonectomy. Methods A total of 106 small-cell lung cancer patients who underwent pneumonectomy between 2006 and 2016 and met the study criteria were identified in the National Cancer Database. Demographics and treatment regimens are described, and overall survival was assessed using Kaplan-Meier and log-rank tests. Results The most common treatment was surgery with adjuvant chemotherapy, followed by surgery only and surgery with neoadjuvant therapy. The 5-year overall survival for the entire cohort after pneumonectomy was 23%. In subgroup analysis, the 5-year overall survival was 30% for guideline-concordant clinical stage I patients and 28% for clinical stage II/III patients who underwent pneumonectomy. There was no statistical difference in survival according to pathologic N disease. Patients with a right-sided pneumonectomy had higher mortality than patients with a left-sided pneumonectomy. Conclusions This study suggests a role for pneumonectomy in clinical stage I and potentially some clinical stage II and III small-cell lung cancer patients. Right-sided pneumonectomy is associated with higher mortality and should be approached with caution. Despite declining trends over the past decades, pneumonectomy is still an effective treatment that is able to achieve acceptable survival outcomes.

Background: Negative symptoms are frequent in patients with schizophrenia and are associated with marked impairments in social functioning. The efficacy of drug-based treatments and psychological interventions on primary negative symptoms remains limited. The Positive Emotions Programme for Schizophrenia (PEPS) is designed to improve pleasure and motivation in schizophrenia patients by targeting emotion regulation and cognitive skills relevant to apathy and anhedonia. The main hypothesis of this study is that patients who attend 8 one-hour sessions of PEPS and treatment as usual (TAU) will have lower total apathy-avolition and anhedonia-asociality composite scores on the Scale for the Assessment of Negative Symptoms (SANS) than patients who attend only TAU. Methods: Eighty participants diagnosed with schizophrenia or schizoaffective disorder were randomized to receive either TAU or PEPS + TAU. The participants were assessed by independent evaluators before randomization (T0), in a post-test after 8 weeks of treatment (T1) and at a 6-month follow-up (T2). Results: The post-test results and 6-month follow-up assessments according to an intention-to-treat analysis showed that the apathy and anhedonia composite scores on the SANS indicated statistically greater clinical improvements in PEPS participants than in non-PEPS participants. In the post-test, anhedonia but not apathy was significantly improved, thus favouring the PEPS condition. These results were sustained at the 6-month follow-up. Conclusions: PEPS is an effective intervention to reduce anhedonia in schizophrenia. PEPS is a short, easy-to-use, group-based, freely available intervention that is easy to implement in a variety of environments (ClinicalTrials.gov ID: NCT02593058).

Resume Cette etude pilote cherche a tester la faisabilite de l’entrainement a la coherence cardiaque avec des personnes atteintes d’un retard intellectuel dans le cadre d’un atelier protege. Un entrainement a la coherence cardiaque est propose aux participants volontaires pour une duree de deux semaines a la prise de travail, matin et apres-midi. Une appreciation des effets de ces exercices respiratoires est effectuee avant et apres entrainement par la mesure d’indices de variabilite cardiaque et une evaluation de la perception du stress professionnel. La comparaison des valeurs recoltees pre- et post-entrainement revele une amelioration significative dans l’activation de la branche parasympathique. L’evaluation des valeurs du RMSSD sont inversement correlees a l’evaluation des participants de leurs stress percus. Ensemble, nos resultats indiquent que la population atteinte de retard intellectuel est receptive a l’apprentissage de la coherence cardiaque et que la baisse de leur stress est liee a une hausse de l’activite inhibitrice parasympathique, plutot qu’a une diminution de l’activite excitatrice sympathique. Les considerations offertes par cette etude exploratoire doivent etre etayees, mais permettent d’ores et deja d’ouvrir de nouvelles perspectives dans la prise en charge de populations pour lesquelles la gestion du stress est mal adaptee.

The Savoring Beliefs Inventory (SBI) is a measure designed to assess attitudes toward savoring positive experience within three temporal orientations: the past (reminiscence), the present moment (present enjoyment), and the future (anticipation). The aim of this study was to validate the structure of the SBI-French version. The scale was tested with 335 French-speaking participants. Two models were estimated: a one-factor model representing a general construct of savoring and a three-factor model differentiating between anticipation, present enjoyment, and reminiscence. Several indicators of model fit were used: the root mean square error of approximation (RMSEA), the comparison fit index (CFI), the Tucker-Lewis fit index (TLI), and the standardized root mean residual (SRMR). A chi-square difference test was used to compare the two models. The model fit of the three-factor model assessed by the SRMR showed to be excellent, while it could be considered as satisfactory according to the CFI and TLI coefficients. RMSEA, however, was slightly less adequate. The model fit for the one-factor model seemed less adequate than the three-factor solution. Further, the chi-square difference test revealed that the three-factor model had significantly better fit than the one-factor model. Finally, the reliability of the four scores (anticipating pleasure, present moment pleasure, reminiscing pleasure, and total score) was very good. These results show that the French version of the SBI is a valid and valuable scale to measure attitudes regarding the ability to savor positive experience, whether it be in anticipation, reminiscence, or the present moment.

Résumé La conscience du trouble ou insight est un concept multidimensionnel incluant la reconnaissance de la maladie la compréhension des effets des médicaments et la reconnaissance des symptômes. L’entraînement métacognitif (EMC) devrait améliorer spécifiquement la reconnaissance des idées délirantes comme faisant partie du trouble par rapport à l’acceptation de la maladie ou la reconnaissance du besoin de traitement. L’amélioration de cette variable ne devrait pas forcément conduire à la dépression. Cinquante deux participants de 18 à 65 ans remplissant les critères de la CIM 10 pour une schizophrénie ou un trouble schizo affectif ont été répartis aléatoirement dans deux groupes un recevant le traitement habituel (TH) et l’autre bénéficiant de l’EMC. Les patients ont été évalués avec la Scale to Assess Unawareness of Mental Disorder (SUMD) avant la randomisation (T0) à la fin de l’EMC (T1) et six mois après le post test (T2). La reconnaissance des idées délirantes comme faisant partie du trouble à T2 est statistiquement et cliniquement significative dans le groupe ayant bénéficié de l’entraînement métacognitif. Ce qui n’est pas le cas pour les autres dimensions de la conscience du trouble ou pour le groupe témoin. L’amélioration de cette variable n’est pas associée à une augmentation de la dépression. L’insight est souvent confondu avec la symptomatologie psychotique. L’estime de soi et la dépression pourraient être associées aux symptômes psychotiques et non pas à la modification de l’insight. SummaryIntroduction Insight is a multidimensional concept including awareness of having a mental illness understanding of the therapeutic effects of medication and recognition of symptoms as part of the disorder (David 1990). The meta cognitive training program (MCT) developed by Moritz et al. (2010) is a new way of approaching the psychological treatment of psychotic symptoms. The principal goal of MCT is to make patients aware of and reduce cognitive biases associated with psychosis. The program focuses on attributional biases jumping to conclusions incorrigibility theory of mind overconfidence in memory errors and negative cognitive schematas. Since the MCT program improves awareness of cognitive biases it should also specifically improve recognition of delusions as part of the disorder compared to acknowledgment of the disease or recognition of the need for treatment. The improvement of this variable should not necessarily lead to depression. Methods Fifty two participants from 18 to 65 meeting the criteria of ICD 10 for schizophrenia or schizoaffective disorder were randomized into two groups: one receiving the usual treatment (TAU) and the other one receiving the TAU + MCT. Patients were assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD) before randomization (T0) at the end of the MCT (T1) and 6 months after the post test (T2). Participants receiving MCT were invited to participate in 8 one hour sessions and received homework assignments. The program is composed of a manual and slides. MCT is currently available in 30 languages and can been downloaded from the following web address: http://www.uke.de/mct. Results The participants undergoing TAU only did not improve on any measure of insight assessed by the SUMD. However participants who followed MCT showed statistically significant results and a moderate to strong effect sizes for understanding the therapeutic effects of drugs (Cohen's d = 0.46) awareness of delusions (Cohen's d = 0.60) and attribution of delusions to the illness (Cohen's d = 0.47) of the SUMD to 6 months follow up (T2). At post test (T1) only awareness of delusions was statistically and clinically significantly improved (Cohen's d = 0.42). Given the number of statistical comparisons a Bonferroni correction was required. This statistical significance was set at P < 0.01. With this rule only awareness of delusions improved (t = 2.9 df (23) P = 0.008 Cohen's d = 0.60) at 6 months follow up. The item of the PANSS depression did not change for the TAU group and moderately improved for the TAU + MCT group but it was not statistically significant. Discussion From a theoretical point of view it is interesting to see that MCT had a specific effect on the most relevant variable confirming certain independence between the variables included in the multidimensional concept of insight. Indeed metacognitive training seeks to improve awareness of cognitive biases associated with delusions and leads to an improvement of awareness of delusions. The improvement of awareness of delusion did not appear to be associated with an increase in depression. This study has some limitations. First these data are secondary outcomes (Favrod et al. 2014) and the sample size was calculated on the basis of the scale “delusions” of Psychotic Rating Scales. In this context the size of the sample may not be large enough to detect effects. Second depression is measured with the PANSS item G6 and not with a full scale depression. However this is an exploratory study to investigate the effect of an intervention on a specific variable of the concept of insight.

The Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS), a measure specifically designed to assess hedonic capacity for social and interpersonal pleasure, was used to evaluate the presence of social anhedonia in patients as well as the general population. The first goal of this study was to validate the structure of the French version of the ACIPS. The second objective was to verify whether a one, two or three factor solution is most appropriate for the ACIPS scale. The French version of the ACIPS was tested on 263 French-speaking pre-graduate students or professional volunteers. For the confirmatory factor analysis, data were treated as categorical ordinal and all the models were estimated using a robust weighted least squares estimator with adjustments for the mean and variance. Three models were estimated. A one-factor model representing a general undifferentiated “pleasure” latent construct was first tested on the 17 ACIPS items. A two-factor model distinguishing anticipatory-pleasure and consummatory-pleasure was tested next. Finally, a three-factor model including subdomains of intimate social interactions, group social interactions, and social bonding was tested. The one and two-factor models showed a somewhat poor fit to the data. However, the goodness of fit of the three factor model was adequate. These results suggest that individuals who enjoyed interaction in one of these three subdomains were more likely to enjoy doing so in the two other domains. However, on the basis of the comparison between the one and three factor models, these three types of interactions may not be considered as indistinguishable. Rather, they represent distinct and theoretically meaningful dimensions. These results show the French version of the ACIPS is a useful and valid scale to measure the capacity of savoring different kinds of social relationships.

Verbal auditory hallucinations can have a strong impact on the social and professional functioning of individuals diagnosed with schizophrenia. The safety-seeking behaviours used to reduce the threat associated with voices play a significant role in explaining the functional consequences of auditory hallucinations. Nevertheless, these safety-seeking behaviours have been little studied. Twenty-eight patients with schizophrenia and verbal auditory hallucinations were recruited for this study. Hallucinations were evaluated using the Psychotic Symptom Rating Scale and the Belief About Voice Questionnaire and safety behaviours using a modified version of the Safety Behaviour Questionnaire. Our results show that the vast majority of patients relies on safety behaviours to reduce the threat associated with voices. This reliance on safety behaviours is mostly explained by beliefs about origin of voices the omnipotence attributed to hallucinations and the behavioural and emotional reactions to the voices. Safety-seeking behaviours play an important role in maintaining dysfunctional beliefs with respect to voices. They should be better targeted within the cognitive and behavioural therapies for auditory hallucinations.

BACKGROUND: Recent literature has distinguished the negative symptoms associated with a diminished capacity to experience (apathy, anhedonia) from symptoms associated with a limited capacity for expression (emotional blunting, alogia). The apathy-anhedonia syndrome tends to be associated with a poorer prognosis than the symptoms related to diminished expression. The efficacy of drug-based treatments and psychological interventions for these symptoms in schizophrenia remains limited. There is a clear clinical need for new treatments. METHODS: This pilot study tested the feasibility of a program to reduce anhedonia and apathy in schizophrenia and assessed its impact on 37 participants meeting the ICD-10 criteria for schizophrenia or schizoaffective disorders. Participants were pre- and post-tested using the Scale for the Assessment of Negative Symptoms (SANS) and the Calgary Depression Scale for Schizophrenia (CDSS). They took part in eight sessions of the Positive Emotions Program for Schizophrenia (PEPS)--an intervention that teaches participants skills to help overcome defeatist thinking and to increase the anticipation and maintenance of positive emotions. RESULTS: Thirty-one participants completed the program; those who dropped out did not differ from completers. Participation in the program was accompanied by statistically significant reductions in the total scores for Avolition-Apathy and Anhedonia-Asociality on the SANS, with moderate effect sizes. Furthermore, there was a statistically significant reduction of depression on the CDSS, with a large effect size. Emotional blunting and alogia remain stable during the intervention. DISCUSSION: Findings indicate that PEPS is both a feasible intervention and is associated with an apparently specific reduction of anhedonia and apathy. However, these findings are limited by the absence of control group and the fact that the rater was not blind to the treatment objectives. CONCLUSIONS: PEPS is a promising intervention to improve anhedonia and apathy which need to be tested further in a controlled study. TRIAL REGISTRATION NUMBER: ISRCTN registry ISRCTN74048461, registered 18 may 2015.

In this review of recent therapeutic developments in psychiatry, we will report on three domains where new strategies have been proposed. First we will discuss the concept of neuroprotection in patients at "ultra high risk" to develop psychosis and the encouraging results of a randomised controlled trial comparing the effect of placebo and fish oil. We will then present the impact of metacognition programs which aim at adding some flexibility to thought processes used by patients with psychosis in order to reduce psychotic symptoms. We finally will report on a program of supported employment which was developed in order to help patients find an active place in society.

In clinical practice, anhedonia and apathy are challenging symptoms of schizophrenia. Anhedonia in schizophrenia appears to be associated with impairment in anticipatory pleasure. However, the problem is complicated since comorbid depression occurs in 50 % of patients and the symptoms of the different disorders may overlap. This chapter presents an intervention to train anticipatory pleasure in patients with schizophrenia. This intervention has been evaluated in an exploratory pilot study. Results show that the patients improved on the anticipatory scale of the Temporal Experience of Pleasure Scale. Patients also increased their daily activities. The program is still being improved and should be tested in a controlled study.