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Depression is common in older individuals and is associated with high disability and mortality. A major problem is treatment resistance: >50% of older patients do not respond to current antidepressants. Therefore, new effective interventions for prevention and treatment of depression in older individuals need to be developed, which requires a better understanding of the mechanisms underlying depression. The pathophysiology of depression is multifactorial and complex. Microvascular dysfunction may be an early and targetable mechanism in the development of depression, notably depression that initiates in late life (late-onset depression). Late-onset depression commonly co-occurs with other diseases or syndromes that may share a microvascular origin, including apathy, cognitive impairment, dementia, and stroke. Together, these disabilities may all be part of one large phenotype resulting from global cerebral microvascular dysfunction. In this review, we discuss the pathophysiology of microvascular dysfunction-related late-onset depression, summarize recent epidemiological evidence on the association between cerebral microvascular dysfunction and depression, and indicate potential drivers of cerebral microvascular dysfunction. We also propose the hypothesis that depression may be a manifestation of a larger phenotype of cerebral microvascular dysfunction, highlight potential therapeutic targets and interventions, and give directions for future research.

Introduction Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects. Objective The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19. Methods We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed. Results Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75–5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91–3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31–7.34; p = 0.010). Conclusion Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-021-01001-0.

Background The perceived importance of clinical empathy may decline among students during medical training. Several interventions have been shown to be effective in promoting or preserving medical students’ empathic abilities, such as empathy skills training or Balint groups. Although narrative medicine training shares some features with these interventions, no randomized study to date examined the efficacy of narrative medicine training. This study aimed to assess the effects of Balint groups and narrative medicine training on clinical empathy measured by the self-rated Jefferson’s School Empathy Scale - Medical Student (JSPE-MS©) among fourth-year medical students. Methods Students who gave their consent to participate were randomly allocated in equal proportion to Balint groups, narrative medicine training or to the control group. Participants in the intervention groups received either seven sessions of 1.5-h Balint groups or a 2-h lecture and five sessions of 1.5-h narrative medicine training from October 2015 to December 2015. The main outcome was the change in JSPE-MS© score from baseline to one week after the last session. Results Data from 362 out of 392 participants were analyzed: 117 in the control group, 125 in the Balint group and 120 in the narrative medicine group. The change in JSPE-MS© score from baseline to follow-up was significantly higher in the Balint group than in the control group [mean (SD): 0.27 (8.00) vs. -2,36 (11.41), t = 2.086, P = 0.038]. The change in JSPE-MS© score in the narrative medicine group [mean (SD): − 0.57 (8.76)] did not significantly differ from the changes in the control group (t = 1.355, P = 0.18) or the Balint group (t = 0.784, P = 0.43). Adjusting for participants’ characteristics at baseline, Balint groups remained associated with better outcomes compared to the control group (β = 2.673, P = 0.030). Conclusions Balint groups may promote clinical empathy to some extent among medical students, at least in the short run.

Context Most medical doctors are likely to work with patients experiencing mental health conditions. However, educational opportunities for medical doctors to achieve professional development in the field of psychiatry are often limited. Simulation training in psychiatry may be a useful tool to foster this development. Objectives The purpose of this study was to assess the effectiveness of simulation training in psychiatry for medical students, postgraduate trainees and medical doctors. Methods For this systematic review and meta-analysis, we searched eight electronic databases and trial registries up to 31 August 2018. We manually searched key journals and the reference lists of selected studies. We included randomised and non-randomised controlled studies and single group pre- and post-test studies. Our main outcomes were based on Kirkpatrick levels. We included data only from randomised controlled trials (RCTs) using random-effects models. Results From 46 571 studies identified, we selected 163 studies and combined 27 RCTs. Interventions included simulation by role-play (n = 69), simulated patients (n = 72), virtual reality (n = 22), manikin (n = 5) and voice simulation (n = 2). Meta-analysis found significant differences at immediate post-tests for simulation compared with active and inactive control groups for attitudes (standardised mean difference [SMD] = 0.52, 95% confidence interval [CI] 0.31-0.73 [I2 = 0.0%] and SMD = 0.28, 95% CI 0.04-0.53 [I2 = 52.0%], respectively), skills (SMD = 1.37, 95% CI 0.56-2.18 [I2 = 93.0%] and SMD = 1.49, 95% CI 0.39-2.58 [I2 = 93.0%], respectively), knowledge (SMD = 1.22, 95% CI 0.57-1.88 [I2 = 0.0%] and SMD = 0.72, 95% CI 0.14-1.30 [I2 = 80.0%], respectively), and behaviours (SMD = 1.07, 95% CI 0.49-1.65 [I2 = 68.0%] and SMD = 0.45, 95% CI 0.11-0.79 [I2 = 41.0%], respectively). Significant differences in terms of patient benefit and doctors' behaviours and skills were found at the 3-month follow-up. Conclusions Despite heterogeneity in methods and simulation interventions, our findings demonstrate the effectiveness of simulation training in psychiatry training.

Les théories profanes émises par les patients et certains ouvrages destinés au grand public alimentent l’idée que le stress psychologique peut influencer le risque de survenue de cancer. Les études consultées sur cette question semblent donner des résultats contradictoires. D’un côté, ces théories peuvent sembler étayées par les résultats d’études expérimentales portant sur les corrélats physiologiques du stress sur des voies neuro-immunoendocrinologiques (perturbations immunitaires, altération de l’axe hypothalamohypophyso- surrénalien), métaboliques et cellulaires (stress oxydatif, dégénérescence cellulaire) pouvant être impliquées dans la tumorigenèse. De l’autre, les études épidémiologiques prospectives fondées sur une méthodologie robuste ne trouvent généralement pas d’association entre exposition au stress et développement ultérieur d’un cancer. Par ailleurs, les méta-analyses suggèrent l’existence de biais de publication pouvant surestimer le poids des études « positives ». Quand bien même une association est retrouvée, le caractère observationnel des études épidémiologiques et donc la possibilité de facteurs de confusion empêchent d’établir un lien de causalité entre l’exposition au stress et un risque majoré de cancer. En ce qui concerne les mécanismes d’une éventuelle relation causale directe, il faut souligner la difficulté d’extrapoler à l’être humain des résultats obtenus chez d’autres animaux, et s’assurer de bien prendre en compte la présence de facteurs comportementaux confondants ou médiateurs comme une mauvaise hygiène de vie alimentaire, la consommation de tabac et d’alcool, les expositions professionnelles, etc. Selon les recommandations du National Cancer Institute (NCI, 2012), les connaissances actuellement disponibles ne permettent pas d’établir un lien de causalité entre stress et augmentation du risque de cancer. Si le professionnel de soin psychique ne doit donc pas cautionner ce lien hypothétique au risque de culpabiliser le patient, il gardera à l’esprit, d’une part, que le cancer peut en revanche générer un stress bien réel au quotidien chez les patients atteints par cette maladie et, d’autre part, que ces théories « profanes » peuvent parfois témoigner d’un mécanisme de défense contre ce stress.

International audience; (1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients’ characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29–0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

Background: Persistent physical symptoms are common after a coronavirus disease 2019 (COVID-19) episode, but their pathophysiological mechanisms remain poorly understood. In this study, we aimed to explore the association between anxiety and depression at 1-month after acute infection and the presence of fatigue, dyspnea, and pain complaints at 3-month follow-up.Methods: We conducted a prospective study in patients previously hospitalized for COVID-19 followed up for 3 months. The Hospital Anxiety and Depression Scale (HAD-S) was administered by physicians at 1-month follow-up, and the presence of fatigue, dyspnea, and pain complaints was assessed at both 1 month and 3 months. Multivariable logistic regressions explored the association between anxiety and depression subscores and the persistence of each of the physical symptom at 3 months.Results: A total of 84 patients were included in this study (Median age: 60 years, interquartile range: 50.5–67.5 years, 23 women). We did not find any significant interaction between anxiety and the presence of fatigue, dyspnea, or pain complaints at 1 month in predicting the persistence of these symptoms at 3 months (all p ≥ 0.36). In contrast, depression significantly interacted with the presence of pain at 1 month in predicting the persistence of pain at 3 months (OR: 1.60, 95% CI: 1.02–2.51, p = 0.039), with a similar trend for dyspnea (OR: 1.51, 95% CI: 0.99–2.28, p = 0.052).Discussion and Conclusion: Contrary to anxiety, depression after an acute COVID-19 episode may be associated with and increased risk of some persistent physical symptoms, including pain and dyspnea.

IntroductionDevelopment of fully internet-based programs could provide a new avenue to improve access to healthcare for problem gamblers. In this project, we aim to assess the efficacy of a web-based cognitive intervention targeting inhibitory control among problem gamblers, using a randomised controlled design. As impaired inhibitory control is involved in self-regulation difficulties in behavioural addictions, it represents a particularly relevant cognitive process to target for an online psychological intervention.Methods and analysisThis will be a single-blinded, randomised, comparative therapeutic web-based, controlled trial. Up to 200 non-treatment seeking adult problem gamblers with a Problem Gambling Severity Index-recent (PGSI-recent) score ≥5 will be included. The intervention will be a computerised cognitive training program targeting inhibitory skills. The comparator, an active control, will be a computerised neutral sensorial program. Both programs will be carried out under similar conditions: biweekly online training for 6 weeks and optional telephone support will be offered to patients for debriefing. The main objective of the study is to assess the clinical efficacy of the online cognitive training program at 6 weeks, measured with the PGSI-recent. The secondary objectives are to assess the efficacy on the gambling behaviour assessed by the account-based gambling data, on the self-reported gambling practice, and on the inhibition performance at the neuropsychological level at 6, 14 and 52 weeks. We will also assess the acceptability of this program and the preferred level of guidance. Data analysis will be in intention-to-treat.Ethics and disseminationThis randomized controlled trial will be executed in compliance with the Helsinki Declaration, and was approved by the local ethics boards (Comité de Protection des Personnes) in October 2017. The findings will be published in peer-reviewed journals.Trial registration numberNCT03673800.

Background: Cognitive complaints are frequent after COVID-19 but their clinical determinants are poorly understood. This study aimed to explore the associations of objective cognitive performances and psychological distress with cognitive complaints in COVID-19 survivors.Materials and Methods: Patients previously hospitalized for COVID-19 in a university hospital during the first wave of COVID-19 pandemic in France were followed-up at 1 month after their admission. Cognitive complaints were self-reported and standardized instruments were used to assess neuropsychological status (Digit Symbol Substitution Test, Semantic Verbal Fluency Test, Mini Mental Status Examination) and psychological distress (Hospital Anxiety and Depression Scale, HADS). Multivariable analyses were adjusted for age, sex, admission in intensive care unit (ICU) and need for oxygen and C-reactive protein.Results: One hundred patients (34% women, median age: 60 years [interquartile range: 49–72)] completed the neuropsychological assessment at follow-up. In multivariable analyses, cognitive complaints at 1-month were associated with greater HADS score (OR for one interquartile range: OR: 1.96, 95% CI: 1.08–3.57) and older age (OR: 1.05, 95% CI: 1.01–1.09) and, negatively, with admission in ICU (OR: 0.22, 95% CI: 0.05–0.90). In contrast, none of the objective neuropsychological test scores was significantly associated with cognitive complaints. Exploratory analysis showed that cognitive complaints were associated with both anxiety and depressive symptoms.Discussion: These preliminary results suggest that cognitive complaints at 1 month after a hospitalization for COVID-19 are associated with psychological distress, independently of objective neuropsychological status. Anxiety and depression symptoms should be systematically screened in patients presenting with cognitive complaints after a severe COVID-19 episode.

International audience; A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43–0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.

International audience

Background In older patients with cancer, depression is difficult to assess because of its heterogeneous clinical expression. The 4-item version of the Geriatric Depression Scale (GDS-4) is quick and easy to administer but has not been validated in this population. The present study was designed to test the diagnostic performance of the GDS-4 in a French cohort of older patients with cancer before treatment. Materials and Methods Our cross-sectional analysis of data from the Elderly Cancer Patient cohort covered all patients with cancer aged ≥70 years and referred for geriatric assessment at two centers in France between 2007 and 2018. The GDS-4’s psychometric properties were evaluated against three different measures of depression: the geriatrician's clinical diagnosis (based on a semistructured interview), the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, and a cluster analysis. The scale's sensitivity, specificity, positive and negative likelihood ratios, and area under the receiver operating characteristic curve (AUROC) were calculated. Results In a sample of 2,293 patients (median age, 81 years; women, 46%), the GDS-4’s sensitivity and specificity for detecting physician-diagnosed depression were, respectively, 90% and 89%. The positive and negative likelihood ratios were 8.2 and 0.11, and the AUROC was 92%. When considering the subset of patients with data on all measures of depression, the sensitivity and specificity values were, respectively, ≥90% and ≥72%, the positive and negative likelihood ratios were, respectively, ≥3.4 and ≤ 0.11, and the AUROC was ≥91%. Conclusion The GDS-4 appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. Implications for Practice Considering the overlap between symptoms of cancer and symptoms of depression, depression is particularly difficult to assess in older geriatric oncology and is associated with poor outcomes; there is a need for a routine psychological screening. Self-report instruments like the 4-item version of the Geriatric Depression Scale appears to be a clinically relevant, easy-to-use tool for routine depression screening in older patients with cancer. Asking four questions might enable physicians to screen older patients with cancer for depression and then guide them toward further clinical evaluation and appropriate care if required.

Background: Low-grade chronic inflammation has been suggested to play a substantial role in the etiology of depression; however, studies on the prospective association between the inflammatory potential of the diet and depression are limited.Objective: The aim of this study was to investigate the association between the inflammatory potential of the diet (measured using the Alternate Dietary Inflammatory Index, ADII) and incident depressive symptoms. We also tested the potential modulating effect of sex, age, BMI, and lifestyle indicators.Methods: The study sample consisted of 26,730 participants (aged 18-86 y) from the NutriNet-Sante study. Baseline ADII was computed using repeated 24-h dietary records collected during the first 2 y of the follow-up. Incident cases of depressive symptoms were defined by a Center for Epidemiologic Studies Depression scale >= 17 for men and >= 23 for women at least once during follow-up. HR and 95% CI were estimated using multivariable Cox proportional hazards models.Results: A total of 2221 incident cases of depressive symptoms were identified over a mean follow-up of 5.4 y. After accounting for a wide range of potential confounders, the highest quartile of the ADII was associated with a 15% (95% CI: 2, 31) increase in the risk of depressive symptoms compared with the lowest quartile. In the stratified analyses, associations were statistically significant only among women (HRquartile4 (vs. quartile1): 1.19; 95% CI: 1.02, 1.37), middle-age adults (HRquartile4 vs. quartile1: 1.16; 95% CI: 1.00, 1.35), and participants with a BMI >= 25 (HRquartile4 vs. quartile1: 1.29; 95% CI: 1.04, 1.60).Conclusions: Overall, a proinflammatory diet was associated with a higher risk of depressive symptoms, especially among women, middle-age adults, and participants with overweight or obesity. These findings contribute to the increasing scientific evidence showing a detrimental role of the proinflammatory diet. The NutriNet-Sante study is registered at clinicaltrials.gov as NCT03335644.

International audience; AIMS: To examine the cross-sectional and longitudinal associations between depressive symptoms and electronic cigarette (e-cig) use in a large population-based sample while taking into account smoking status and sociodemographic confounders.METHODS: Participants from the French Constances cohort were included from February 2012 to December 2016. Smoking status, e-cig use (never/ever/current) and nicotine concentration were self-reported. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regressions were used to provide odds ratios (ORs) and 95% confidence intervals (95%CI) of e-cig use according to depressive symptoms, adjusting for age, sex and education.RESULTS: In cross-sectional analyses (n = 35,337), depressive symptoms (i.e. a CES-D score ≥ 19) were associated with both ever (OR [95%CI]: 1.67 [1.53-1.82]) and current (1.73 [1.53-1.96]) e-cig use with a dose-dependent relationship (p-trend

Background Medial prefrontal cortex (MPFC) activity during self-referential processing has been associated with rumination and found aberrant in depression. We investigated whether this aberrant activity reflects a trait marker that persists in remitted patients. Methods Twenty-five patients fully remitted from major depression for at least 6 months, and 29 matched healthy controls were scanned with fMRI while presented with personality trait words in two conditions: Self condition asked whether the trait described themselves; General condition asked whether the trait was generally desirable. Contrasts-of-interest were examined in a factorial model and rumination correlates were examined in 2-sample t-tests with Ruminative Response Style score as covariate. All findings were reported at a conservative p Results Self-referential processing increased anterior cortical midline activity to a similar extent in both groups. Dorsal anterior cingulate cortex (MNI(x,y,z) = -12,20,26) and dorsal MPFC (MNI(x,y,z) = -6,46,40) activity during self-referential processing was positively associated with rumination in healthy control subjects and negatively associated with rumination in remitted patients. Limitations A longitudinal design tracking the relationship between rumination and MPFC activity would have aided the interpretation of our findings as to whether high ruminators are exhibiting an adaptive process to maintain remission or whether it represents a maladaptive process considering that high ruminators have an increased vulnerability for relapse. Conclusions The association between increased anterior cortical midline activity during self-referential processing and rumination differentiated healthy controls from formerly depressed patients. Self-referential neural processing during remission from depression may depend on the cognitive tendencies to ruminate.

An observatory of sexual harassment and psychological abuse was set up at one of France's largest schools of medicine to both quantify and reduce sexual harassment or psychological abuse of medical students.Over a 2-year period, we described the evolution of sexual harassment and psychological abuse and explored for associated factors. Moreover, a qualitative analysis using an inductive approach was performed from students' verbatim.2795 responses were collected. Sexual harassment was reported in 7% and psychological abuse in 15%, at baseline, and decreased after the observatory was set up. Women had higher odds of being a victim of sexual harassment. Older students reported less often psychological abuse and being a witness of sexual harassment. Surgery departments were associated with up to 5.7-fold increased odds of sexual harassment. Surgery and pediatrics departments were associated with a 2-fold increased odds of psychological abuse. Qualitative analysis revealed four categories: humiliation, the feeling of inferiority, sexual harassment, and manifestations of violence.During clerkships, factors associated with higher odds of sexual harassment and psychological abuse were female gender, younger age, and departments of surgery. Setting up such an observatory may contribute to reduce this burden and provide a useful tool to raise awareness.

INTRODUCTION: Psychotropic drugs such as anxiolytics, antidepressants and antipsychotics may have anticholinergic properties that could directly affect patients' cognition. OBJECTIVES: Our objective was to assess the relationship between exposure to anticholinergic-positive (AC+) psychotropic drugs and cognitive impairment compared with psychotropic drugs without anticholinergic activity (AC-). METHODS: This analysis included participants (aged 45-70 years) enrolled between January 2012 and October 2017 in the CONSTANCES cohort treated with psychotropic drugs (antidepressants n = 2602, anxiolytics n = 1195, antipsychotics n = 197) in the 3 years preceding cognitive assessment. Within each drug class, the Anticholinergic Cognitive Burden scale was used to classify drugs as either AC+ or AC-. Cognitive impairment was defined as a score below - 1 standard deviation from the standardized mean of the neuropsychological score. We used multiple logistic regression models and matching on propensity score to estimate the relationship between anticholinergic activity and cognitive impairment. RESULTS: Our analyses did not show any increased risk of cognitive impairment for AC+ antidepressants and anxiolytics, with the exception of a slight increase for AC+ antidepressants in episodic memory (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.05-1.36). Conversely, we found a more marked increase in risk with AC+ antipsychotics on executive function (Trail Making Test-A [TMT-A], OR 4.49 [95% CI 2.59-7.97] and TMT-B, OR 3.62 [95% CI 2.25-5.89]). CONCLUSION: Our results suggest there is no clinically relevant association between the anticholinergic activity of antidepressant and anxiolytic drugs and cognitive impairment in middle-aged adults. An association could exist between AC+ antipsychotics and executive function.

Background Inconsistent association between depression and hypertension has been highlighted. The association of depression with blood pressure (BP) might depend upon socioeconomic status (SES), but evidence remains weak. Objectives This study aimed to examine how the associations between depressive symptoms and BP levels and hypertension and then, according to SES variables (education, income, occupational status). Methods Among 66,478 volunteers of the French CONSTANCES cohort (31,093 men; mean age (standard deviation): 47.8 (12.9) years), depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). Overall associations between depressive symptoms and BP and hypertension were estimated using regressions and by stratifying on SES. Results SES were associated with BP in both genders. CES-D score was negatively associated with systolic BP (SBP) in women (b=-0.62 95%CI [-1.03; -0.21] and in men (b=-1.03 95%CI [-1.45; -0.61]) but not with diastolic BP (DBP) in both genders. In women, the decrease in SBP and DBP was more pronounced as educational level increases (p for interaction: 0.012 and 0.013, respectively). In men, few interactions were observed between CES-D score and SES factors for BP levels. The association between CES-D score and hypertension was significant for men, OR=0.86, 95%CI [0.80; 0.93] but not for women, OR=1.03, 95%CI [0.96; 1.10]. No interactions were observed between CES-D score and SES for hypertension. Conclusion Gender differences were observed for considering depressive symptoms according to SES factors for BP variation and hypertension. In women, educational level was the SES factor which has the main modifying effect on this association.

To review evidence regarding the association between bipolar disorder and schizophrenia, henceforth referred to as severe mental disorders (SMD), and cardiovascular morbidity and mortality, its mechanisms, and the interventions to reduce this burden. Much of the loss in life expectancy in people with SMD remains driven by cardiovascular mortality. Antipsychotics and mood stabilizers are associated with negative cardio-metabolic outcomes, but large inter-individual differences are observed, and not treating SMD might be associated with even greater cardiovascular mortality. Classical modifiable cardiovascular risk factors remained inadequately screened and, once identified, too seldom treated in people with SMD. After a myocardial infarction, aggressive tertiary prevention may be as effective in people with SMD as in the general population but is less prescribed. Reduced healthcare quality and increased prevalence of cardiovascular risk factors may not fully explain the excess cardiovascular mortality associated with SMDs, which themselves should be considered risk factors in risk calculators. Hazardous health behaviors, the cardio-metabolic adverse effects of medications, and a reduced access to quality healthcare remain priority targets for intervention.

Summary Background Since the first successful facial transplantation in 2005, the benefits of this procedure in terms of aesthetics, functionality, and quality of life have been firmly established. However, despite immunosuppressive treatment, long-term survival of the allograft might be compromised by chronic antibody-mediated rejection (CAMR), leading to irreversible necrosis of the tissue. In the absence of therapeutic options, this complication is inevitably life-threatening. Methods We report facial retransplantation in a man, 8 years after his first facial transplantation because of extensive disfigurement from type 1 neurofibromatosis and 6 weeks after complete loss of his allograft due to severe CAMR. We describe the chronology of immune-related problems that culminated in allograft necrosis and the eventual loss of the facial transplant, the desensitisation protocol used for this highly immunosensitised recipient, the surgical technicalities of the procedure, the specific psychological management of this patient, and the results from follow-up at 30 months. Findings Although the patient had a complicated postoperative course with numerous immunological, infectious, cardiorespiratory, and psychological events, he was discharged after a hospital stay of almost 1 year. He has since been able to re-integrate into his community with acceptable restoration of his quality of life. Interpretation This clinical report of the first documented human facial retransplantation is proof-of-concept that the loss of a facial transplant after CAMR can be mitigated successfully by retransplantation combined with an aggressive desensitisation process. Funding Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris.

Highlights • During the COVID-19 outbreak, many radiologists expressed anxiety, depression and insomnia symptoms. • Working in public hospital was a major protective factor for mental issues. • Restricted access to education, past medical history and exposition to COVID-19 were common risks factor of anxiety or depression., Purpose The COVID-19 pandemic has led to an urgent reorganisation of the healthcare system to prevent hospitals from overflowing and the virus from spreading. Our objective was to evaluate the socioeconomic and psychological impact of the COVID-19 outbreak on radiologists. Material and methods French radiologists were invited to answer an online survey during the pandemic through mailing lists. The questionnaire was accessible for nine days. It covered socio-demographic information, exposure to COVID-19 at work and impact on work organisation, and included the Insomnia Severity Index and Hospital Anxiety and Depression Scale. Outcomes were moderate to severe insomnia, definite symptoms of depression or anxiety. Risk and protective factors were identified through multivariate binary logistic regression. Results 1515 radiologists answered the survey. Overall, 674 (44.5 %) worked in a highCOVID-19 density area, 671 (44.3 %) were women, and 809 (53.4 %) worked in private practice. Among responders, 186 (12.3 %) expressed insomnia, 222 (14.6 %) anxiety, and 189 (12.5 %) depression symptoms. Lack of protective equipment, increased teleradiology activity and negative impact on education were risk factors for insomnia (respectively OR [95 %CI]:1.7[1.1−2.7], 1.5[1.1−2.2], and 2.5[1.8−3.6]). Female gender, respiratory history, working in COVID-19 high density area, increase of COVID-19 related activity, and impacted education were risk factors for anxiety (OR[95 %CI]:1.7[1.2−2.3], 2[1.1−3.4], 1.5[1.1−2], 1.2[1−1.4], and 2.1[1.5−3]). Conversely, working in a public hospital was a protective factor against insomnia, anxiety, and depression (OR[95 %CI]:0.4[0.2−0.7], 0.6[0.4−0.9], and 0.5[0.3−0.8]). Conclusions During COVID-19 pandemic, many radiologists expressed depression, anxiety and insomnia symptoms. Working in a public hospital was a protective factor against every psychological symptom. Socio-economic impact was also major especially in private practice.

Aims Depression is associated with increased risk of cardiovascular disease (CVD) and the role of poor medical adherence is mostly unknown. We studied the association between depressive symptoms and non-adherence to medications targeting treatable cardiovascular risk factors in the CONSTANCES population-based French cohort. Methods and results We used CONSTANCES data linked to the French national healthcare database to study the prospective association between depressive symptoms (assessed at inclusion with the Center for Epidemiological Studies Depression scale) and non-adherence to medications (less than 80% of trimesters with at least one drug dispensed) treating type 2 diabetes, hypertension, and dyslipidaemia over 36 months of follow-up. Binary logistic regression models were adjusted for socio-demographics, body mass index, and personal history of CVD at inclusion. Among 4998 individuals with hypertension, 793 with diabetes, and 3692 with dyslipidaemia at baseline, respectively 13.1% vs. 11.5%, 10.5% vs. 5.8%, and 29.0% vs. 27.1% of those depressed vs. those non-depressed were non-adherent over the first 18 months of follow-up (15.9% vs. 13.6%, 11.1% vs. 7.4%, and 34.8% vs. 36.6% between 19 and 36 months). Adjusting for all covariates, depressive symptoms were neither associated with non-adherence to medications for hypertension, diabetes, and dyslipidaemia over the first 18 months of follow-up, nor afterwards. Depressive symptoms were only associated with non-adherence to anti-diabetic medications between the first 3–6 months of follow-up. Conclusion Non-adherence to medications targeting treatable cardiovascular risk factors is unlikely to explain much of the association between depressive symptoms and CVD at a population level. Clinicians are urged to search for and treat depression in individuals with diabetes to foster medications adherence.

Background The prevalence of psychological symptoms and the co-occurrence of substance abuse disorders in adult patients with Langerhans cell histiocytosis (LCH) has not been previously explored. We aimed to use validated scales to evaluate depression and anxiety symptoms experienced by adult LCH patients. Methods In this cross-sectional study, all consecutive adult LCH patients seen at our national reference center between January 2012 and January 2013 were asked to complete the following instruments: the Hospital Anxiety and Depression scale (HADS); Barratt Impulsiveness Scale, Version 10 (BIS-10); and Cannabis Use Disorders Identification Test (CUDIT). Self-reported scores on these scales were used to determine the point prevalence of clinically significant psychological symptoms and substance use disorders in LCH patients. Patient profiles in terms of psychological features were assessed by principal component analysis including the HADS and BIS-10 instruments values, followed by hierarchical clustering. Fisher exact tests and Wilcoxon tests were used to examine the associations between disease-related parameters and high levels of anxiety and impulsivity. Results Seventy-one adult LCH patients, mainly with pulmonary LCH (PLCH), completed the evaluations. Clinically significant anxiety and depression symptoms were reported by 22 (31%) and 4 (6%) subjects, respectively. Impulsivity was detected in 14% (10/71) of the patients. Seventeen percent (12/71) of the patients used cannabis on a regular basis, with 50% of these individuals (6/12) exhibiting scores consistent with cannabis use disorder. Three derived clusters of patients were identified in the principal component analysis; these patient clusters differed in successful weaning from tobacco at the time of evaluation (p = 0.03). In univariate analyses, isolated PLCH and the use of psychotropic treatments were statistically associated with clinically significant anxiety symptoms. Conclusions High levels of anxiety and impulsivity are common in adult patients with LCH. The consequences of these symptoms for the management of LCH patients warrant further evaluation.

Cross-sectional results have suggested a linear association between the number of dietary exclusions and depressive symptoms. This longitudinal study aimed to examine the direction of this association. Methods: In the population-based Constances cohort, depressive symptoms were defined by a score &ge, 19 on the Centre of Epidemiologic Studies-Depression (CES-D) scale. Diet was measured with a 24-item qualitative food frequency questionnaire (FFQ). Both variables were available at inclusion (from 2012 to 2014) and on follow-up (2015 for the CES-D and 2017 for diet). Food exclusion was categorized into five different groups: No exclusion, exclusion of one, two, three, or &ge, 4 food groups according to the self-reported number of food groups rarely or never consumed. Logistic regressions were conducted, either taking depressive symptoms as the outcome on follow-up with dietary exclusions at baseline as predictor or with the opposite, adjusting for age, sex, education, income, alcohol intake, smoking, physical activity, and anemia. The path analysis included outcomes and covariates in one model. Results: The median follow-up was three years. A total of 29,337 participants (53.4% women, 48.15 &plusmn, 12.9 y.o.) had complete CES-D data and 25,356 (53.56% women, 49.05 &plusmn, 12.8 y.o.) FFQ data. Dietary exclusion at inclusion predicted depressive symptoms at follow-up (odds ratio [95% confidence interval]: 2.35 [1.62&ndash, 3.40] for &ge, 4 excluded items compared to no exclusions). Depressive symptoms at inclusion predicted dietary exclusions at follow-up (3.45 [1.93&ndash, 6.16] for &ge, 4 excluded items). In the path analysis, the standardized estimate of the association between dietary exclusions at inclusion and depressive symptoms at follow-up was by far higher than the opposite (0.1863 and 0.00189, respectively, both p &lt, 0.05). Conclusions: The association of dietary exclusion with subsequent depression is stronger than the opposite association.

International audience; INTRODUCTION - We examined whether duration of electronic cigarette (e-cigarette) use could be associated with smoking reduction or cessation attempt. METHODS - 5,409 current smokers at baseline enrolled in the French CONSTANCES cohort in 2015 or 2016 were included. Duration of e-cigarette use was categorized as follows: never; former user for more than one year; former user for less than one year; new user for less than one year; return to use for less than one year; regular use for one to two years; regular use for more than two years. Two outcomes were considered at one-year of follow-up: change in the number of cigarettes per day and cessation attempt. RESULTS - Compared to never users, former users had an increase in the number of cigarettes per day at follow-up (B = 0.95[95%CI:0.57-1.33] and B = 1.03[95%CI:0.47-1.59] for former users of more than one year and less than one year, respectively). Compared to never users, all categories of current users had a decrease in the number of cigarettes per day (B = -3.31[95%CI:-4.07;-2.54] and B = -4.18[95%CI:-5.06;-3.29] for new users of less than one year and users of more than two years, respectively). Compared to never users, former users had a decreased likelihood of cessation attempt (OR = 0.80[95%CI:0.67-0.95] and OR = 0.77[95%CI:0.60-0.99] for former users of more than one year and less than one year, respectively). Compared to never users, all categories of current users had an increased likelihood of cessation attempt (OR = 3.12[95%CI:2.32;4.19] and OR = 3.36[95%CI:2.39;4.72] for new users of less than one year and users of more than two years, respectively). CONCLUSIONS - E-cigarette use was associated with smoking reduction and cessation attempt for individuals who have used it for less than one year and additional benefits are expected to occur with a longer duration of use. Former users of e-cigarettes had poorer outcomes than those who have never used them.

International audience; Objective: People with panic disorder are at increased risk of suicide. Multiple factors influence their risk suggesting a need to combine them into an integrative model to develop more effective suicide prevention strategies for this population. In this report, we sought to build a comprehensive model of the 3-year risk of suicide attempt in individuals with panic disorder using a longitudinal nationally representative study, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; wave 1, 2001-2002; wave 2, 2004-2005). Method: We used structural equation modeling to simultaneously examine effects of six broad groups of clinical factors previously identified as potential predictors of suicide attempt in adults with panic disorder: 1) severity of panic disorder, 2) severity of comorbidity, 3) prior history of suicide attempt, 4) family history of psychiatric disorders, 5) sociodemographic characteristics and 6) treatment-seeking behavior. Results: The 3-year prevalence rate of suicide attempt was 4.6%. A general psychopathology factor, lower physical health-related quality of life, prior suicide attempt and a greater number of stressful life events at baseline significantly and independently predicted suicide attempt between the two waves (p < .05). R-square of the models ranged from 0.47 to 0.50. Conclusion: This model may help inform future research and identify high-risk individuals among adults with panic disorder.

Background Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. Methods We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. Results Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. Conclusion Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

International audience; Objectives: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic.Methods: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms.Results: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications.Conclusions: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.

Anemia is known to be associated with depression both in community and clinical populations. However, it is still unknown if this association depends or not on antidepressant intake. We investigated the respective association of depression and antidepressant intake with low hemoglobin level in a large community-based cohort. In 8640 volunteers aged 50 to 75 recruited between June 2008 and June 2012 in Paris (France), we assessed hemoglobin levels (g/dl), depressive symptoms and antidepressant intake. We examined the association of both depression and antidepressant intake with hemoglobin level, adjusting for numerous socio-demographic and health variables. We also assessed the association with specific antidepressant classes. Depression and anti-depressant intake were independently associated with lower hemoglobin level (beta = -0.074; p = .05 and beta = -0.100; p = .02 respectively in the fully-adjusted model). Regarding antidepressant classes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (beta = -0.11; p = .01). To conclude, both depression and antidepressant intake were associated with lower hemoglobin level. In particular, as SSRI or SNRIs intake was also related to lower hemoglobin level, these classes should be used with caution in depressed individuals at risk for anemia.

International audience; Ranking antidepressants according to their acceptability (i.e. a combination of both efficacy and tolerability) in the general population may help choosing the best first-line medication. This study aimed to rank antidepressants according to the proportion of filled prescription sequences consistent with a continuation of the first treatment versus those consistent with a change. A first step was validating this measure as a proxy of acceptability by examining the association of these two kinds of sequences with levels of depressive symptoms. Among 64,467 individuals included in the French population-based Constances cohort, reimbursements of antidepressants from January 2009 to December 2015 were extracted from the French national health insurance system claims database. Depressive symptoms were measured at inclusion with the Center for Epidemiologic Studies-Depression scale (CES-D). Between January 2010 and December 2015, 6675 participants newly initiated an antidepressant (34.5% men, mean (SD) age: 48.3 (12.1) years). Among the subsample of participants included during the six-month period following treatment initiation, individuals with continuation sequences had lower levels of depressive symptoms than those with change sequences (mean (SE) CES-D score: 18.9 (0.8) versus 26.5 (2.1), p < 0.001). According to the continuation/change ratio observed over this six-month period in all participants, escitalopram ranked first, followed by sertraline, venlafaxine, citalopram, fluoxetine and paroxetine. In an independent replication sample representative of the French national population, the same six medications ranked first, with escitalopram remaining in first place. The proportion of filled prescription sequences consistent with a continuation versus a change of the first prescribed treatment may provide a widely available measure of antidepressant acceptability in community practice.

International audience; Background: Several modifiable lifestyle indicators, including diet, smoking, alcohol consumption, weight and physical activity have been associated with depression; however, their combined effect has been less studied. The aim of this study was to calculate a Healthy Lifestyle Index (HLI) composed of the 5 above-mentioned indicators and investigate its association with incident depressive symptoms. Methods: The study sample consisted of 25,837 participants from the NutriNet-Sante study, initially free of depressive symptoms. The HLI was computed by assigning 1 point to each lifestyle indicator namely healthy diet, healthy weight, moderate or high physical activity, never smoking and low alcohol consumption. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CES-D). Hazard Ratios were estimated using Cox proportional hazards models and population attributable risks (PAR) were calculated. Results: A total of 2112 incident cases of depressive symptoms were identified over a mean follow-up of 5 years. After accounting for a wide range of potential confounders, a 1-point increase in the HLI was associated with a 10% (95% CI 6%; 13%) reduction in the risk of depressive symptoms. The estimated PAR representing the proportion of cases that are attributable to non-adherence to specific healthy lifestyle indicators were 8% for healthy diet, 5% for healthy weight, 5% for non-smoking and 14% for the non-adherence to a combination of healthy diet, healthy weight and non-smoking. Limitations: Some unmeasured factors related to both depression and lifestyle indicators, such as family history of depressive disorder, stressful life events, and sleep disorders might have led to potential residual confounding. Conclusions: Modifying unhealthy lifestyles, especially diet, weight and smoking, is a potential target of major interest in the prevention of depressive symptoms in adults.

OBJECTIVE: The aim was to investigate the potential association between hearing impairment and incident depressive symptoms.METHODS: Using a prospective community-based cohort study in France (the Paris Prospective Study III), participants aged 50-75 years were recruited between 2008 and 2012 and thereafter followed up every 2 years up to 2018. Hearing impairment, measured at study recruitment by audiometry testing, was defined as a pure tone average >25 decibels in the better ear. Incident depressive symptoms, measured using the validated 13-item Questionnaire of Depression 2nd version, was assessed during follow-up. Multivariate generalized estimating equations were used to compute odds ratio (OR) and 95% confidence intervals (CI).RESULTS: Among 7591 participants free of depressive symptoms at baseline (mean age 59.8 years, 63% of men), 14.3% had hearing impairment. Over 6 years of follow-up, 479 subjects (6.3%) had incident depressive symptoms. The OR for incident depressive symptoms was 1.36 for subjects with baseline hearing impairment (95% CI, 1.06-1.73). A pooled analysis of 4 published prospective studies yielded a multivariable relative risk of baseline hearing impairment for incident depressive symptoms of 1.29 (95% CI, 1.09-1.53).CONCLUSIONS: In this community-based prospective cohort study of participants aged 50 to 75 years, baseline hearing impairment was associated with a 36% increased odds of incident depressive symptoms. (C) 2019 Elsevier Inc. All rights reserved.

International audience; BACKGROUND - Recent evidence suggests that the association of psychological variables with the risk of coronary heart disease (CHD) might depend upon socioeconomic status (SES). However, it is unclear whether the association between depressive symptoms and CHD risk might differ according to three SES indicators (education, occupational status and household monthly income). METHODS - Among 34,836 working participants of the French CONSTANCES cohort (16,221 men, mean age [SD]: 44.0 [10.4] years) without history of cardiovascular disease, depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). The Framingham risk equation calibrated to the French population estimated the participant's 10-year risk of CHD. Associations between depressive symptoms and CHD risk were estimated using linear regression models in SES strata. RESULTS - The estimated 10-year risk of CHD was 16.9% in men and 1.8% in women. In men, the increased CHD risk in those with (versus without) depressive symptoms was more pronounced as occupational status decreased, being 0.65% (−0.57; 1.88), 1.58% (0.50; 2.66) and 3.19% (1.30; 5.07) higher in individuals of high, medium and low occupational status, respectively (p for interaction: 0.01). In contrast, effect modification by education or household income was less evident, despite similar trends. In women, no effect modification was found whatever the SES indicator. CONCLUSIONS - Depressive symptoms and 10-year estimated CHD risk were more tightly linked in individuals of lower SES, at least in men. Occupational status was the SES indicator that displays the most obvious effect modification on this association.

Les personnes atteintes de troubles mentaux severes— schizophrenie en particulier—presentent une surmortalite de cause naturelle incluant la mortalite par cancer. En depit d’une exposition plus importante a certains facteurs de risque de cancers, comme le tabagisme, ces personnes beneficient moins souvent de mesures de prevention et de depistage. Les cancers diagnostiques le sont a un stade plus tardif, et la prise en charge therapeutique est de moindre qualite qu’en population generale. Les causes de cette perte de chances sont multiples et accessibles a des mesures correctives.

Background Heavy drinkers are at high risk for suicide attempt and suicide. Multiple factors, when examined in isolation, have been implicated in the risk of suicide attempt in this population. In this report, we present a comprehensive model of the 3-year risk of suicide attempt in heavy drinkers using a longitudinal nationally representative study, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; wave 1, 2001–2002; wave 2, 2004–2005). Methods We used structural equation modeling to simultaneously examine effects of four broad groups of clinical factors previously identified as potential predictors of attempted suicides: 1) alcohol use disorder severity, 2) severity of comorbidity, 3) sociodemographic characteristics and 4) help-seeking for alcohol problems. Heavy drinking was defined as drinking 5 or more drinks in a day more than once a week in the month prior to Wave 1. Results About 1.5% of the 1573 heavy drinker participants (i.e., 5.1% of the NESARC sample) attempted suicide during the 3-year follow-up period. After adjusting for all other factors, several factors independently predicted attempted suicides: the alcohol use disorder liability factor measured by DSM-IV-TR criteria for alcohol abuse and dependence and two dimensions of psychopathology, the general psychopathology factor accounting for the shared effects of all comorbid psychiatric disorders and the externalizing dimension accounting for the shared effects of comorbid substance use disorders. No other factor predicted this risk in addition. Conclusion This model may help identify individuals with heavy drinking at high risk of suicide and develop more effective suicide prevention strategies.

L’empathie, qui est au cœur de la relation medecin-patient, declinerait pendant les etudes medicales. En France, les etudiants de 4eme annee, sont pour la premiere fois en responsabilite avec des patients. Une etude controlee randomisee multisite a evalue les effets sur l’empathie d’un groupe de Formation a la Relation Therapeutique (FRT) type groupe Balint. L’empathie evaluee par la JSPE-MS© (Jefferson’s School Empathy Scale - Medical Student) a ete significativement superieure dans le groupe FRT. L’utilisation de la FRT peut ameliorer l’empathie des etudiants en medecine.

Low-dose infusion of ketamine may have rapid antisuicide properties. Such a treatment may therefore be useful in the general hospital to prevent suicide in an environment that cannot be made safe enough. We report on the use of ketamine as an efficient, well-tolerated treatment for persistent suicidal ideation in a patient hospitalized in a general hospital after a severe suicide attempt. Based on data in the literature, we suggest that the benefit-risk ratio for ketamine use in such a context is highly favorable.

The potential benefit of breast cancer screening is mitigated by the risk of false positives and overdiagnosis, thus advocating for a more personalized approach, based on the individual benefit‐harm balance. Since personality might influence the women's appraisal of this balance, this prospective observational cohort study examined whether it could influence mammography use. A total of 2691 postmenopausal women of the GAZEL Cohort Study completed the Bortner Type A Rating Scale and the Buss and Durkee Hostility Inventory in 1993. Associations between personality scores and subsequent mammography use, self‐reported through up to five triennial follow‐up questionnaires, were estimated with Odds Ratio (OR) and 95% confidence interval (CI) with logistic mixed model regressions, adjusting for age, occupational grade, marital status, family history of breast cancer, age at menarche, age at first delivery, gynecological follow‐up, hormone therapy use, and depressive symptoms. Individual propensity scores were used to weight the analyses to control for potential selection biases. More than 90% of the participants completed at least two follow‐up questionnaires. Type A personality, but not hostility, was associated with mammography use in both univariate (crude OR [95% CI]: 1.62 [1.24–2.11], P

Introduction The PI3K/Akt/mTOR pathway plays a critical role in cancer cell growth, proliferation and angiogenesis, but also in brain homeostasis and the pathophysiology of mood disorders. The impact of the mTOR inhibitor everolimus on the mood of breast cancer patients is unknown. Materials and methods Consecutive, post-menopausal metastatic breast cancer patients receiving hormone therapy +/- everolimus were prospectively followed-up using the Beck Depression Inventory (BDI) and the MADRS (Montgomery and Asberg Depression Rating Scale) questionnaires. Results Post hoc tests comparing everolimus + hormonotherapy to hormonotherapy alone demonstrated a significant effect of everolimus after 6 weeks of treatment on BDI scores (t(1,38) = -2.0716, p 0.05), and after 3 weeks (t(1,38) = -3.9165, p 0.001) and 6 weeks of treatment (t(1,38) = -2.0373, p 0.05) on MADRS scores. Analysis within each treatment group showed that the effect of time since treatment initiation on BDI and MADRS scores was specifically observed in the everolimus + hormonotherapy group (F(2,34) = 11.875, p 0.001 and F(2,34) = 7.820, p 0.01 respectively), but not in the hormonotherapy alone group (F(2,34) = 1.671, p 0.2 and F(2,34) = 0.830, p 0.2 respectively). Conclusions The mTOR inhibitor everolimus induces significant mood alterations in breast cancer patients. The evaluation of psychiatric symptoms is not only mandatory in the context of phase 1, dose-finding studies of PI3K/Akt/mTOR inhibitors, but is also clinically relevant in daily practice.

International audience; Objectives Knowledge about moderation of the association between hearing loss and depression is scant. We investigated dyslipidemia as a potential moderator of the association between hearing/hearing loss and depressive symptoms. Design Cross-sectional study. Setting General population-based cohort in France (SU.VI.MAX 2; 2007-2009). Participants N= 4,307 adults (mean age = 61.5 +/- 6.1 y; 59.6% women). Measurements A score ≥ 16 on the Center for Epidemiologic Studies Depression Scale defined presence of depressive symptoms. Mean hearing level for each ear was defined as the pure-tone average of the following thresholds: 0.5, 1.0, 2.0 and 4.0 kHz; the value for the better hearing ear was retained for analysis. Hearing loss was defined as inability to hear at thresholds ≥ 25 dB in both ears. A subjective measure of perceived hearing loss was also used. Serum triglyceride, total-, LDL- and HDL-cholesterol concentrations were assessed in fasting blood samples and established cutoffs were used in multivariable logistic regression models. The interaction between hearing/hearing loss (independent variables) and each of the four lipid parameters was tested. Results Even though the interaction tests regarding LDL-, HDL- cholesterol, and triglyceride status were statistically significant, the subgroup analyses revealed few significant and somewhat unexpected findings. In fact, among individuals with low LDL-cholesterol, unlike their counterparts with high LDL-cholesterol, there was an inverse association between hearing level in the better hearing ear and depressive symptoms (OR= 0.94; 95% CI: 0.89- 0.99). Regarding the subjective measure of hearing, a few of the dyslipidemia-moderated associations were statistically significant, albeit not all in the predicted direction. Conclusion The findings provide some support for moderation of the association between hearing/hearing loss and depressive symptoms by dyslipidemia, with important lipid-specific and hearing measure-specific differences. The results could serve as impetus for future investigations in order to identify and target population subgroups with increased vulnerability to depression in the context of both sensory disability and aging.

Background : Previous studies that examined the association between daily alcohol consumption and sickness absences (SA) were mostly retrospective and did not take into account the characteristics of SA. : A total of 9907 daily drinkers (8442 men and 1465 women) of the GAZEL prospective cohort were included. Daily alcohol consumption over the three previous years was self-reported at baseline and categorized as low, moderate, high or very high risk according to the World Health Organization. Duration of SA (short: ≤7 days; moderate: 8-28; long: >28) was collected from administrative records as well as causes for long SA. Negative binomial regression models were used to estimate Risk Ratios of SA according to alcohol consumption with low-risk category as reference. : Duration of follow-up (in years) for SA was 8.4 ± 3.7 in men and 11.2 ± 5.4 in women. Increasing alcohol consumption predicted increasing risk of SA with a dose-response relationship ( P < 0.01 for men; P = 0.01 for women). In men, strength of this association increased with SA duration [e.g. RRs from 1.41 (95% CI: 1.12-1.79) to 2.12 (95% CI: 1.49-3.00) in the very high-risk category, for short and long SA, respectively]. In men, even a moderate consumption predicted increased risk of SA whatever their duration (RR = 1.15; 95% CI: 1.07-1.23). In women, a moderate consumption predicted only long SA (RR = 1.22; 95% CI: 1.00-1.50). Daily alcohol consumption was associated with almost all causes of long SA in men, and with respiratory diseases, digestive diseases and injury in women. : We found a dose-response relationship between daily alcohol consumption and the risk of SA. Even moderate consumption could increase this risk, particularly in men.

International audience

Little is known about the respective effects of depression and cognitive impairment on quality of life among older adults with schizophrenia spectrum disorder.We used data from the Cohort of individuals with Schizophrenia Aged 55-years or more (CSA) study, a large multicenter sample of older adults with schizophrenia or schizoaffective disorder (N = 353). Quality of life (QoL), depression and cognitive impairment were assessed using the Quality of Life Scale (QLS), the Center of Epidemiologic Studies Depression scale and the Mini-Mental State Examination, respectively. We used structural equation modeling to examine the shared and specific effects of depression and cognitive impairment on QoL, while adjusting for sociodemographic characteristics, general medical conditions, psychotropic medications and the duration of the disorder.Depression and cognitive impairment were positively associated (r = 0.24, p 0.01) and both independently and negatively impacted on QoL (standardized β = -0.41 and β = -0.32, both p 0.01) and on each QLS quality-of-life domains, except for depression on instrumental role and cognitive impairment on interpersonal relations in the sensitivity analyses excluding respondents with any missing data. Effects of depression and cognitive impairment on QoL were not due to specific depressive symptoms or specific cognitive domains, but rather mediated through two broad dimensions representing the shared effects across all depressive symptoms and all cognitive deficits, respectively.Because of the cross-sectional design of this study, measures of association do not imply causal associations.Mechanisms underlying these two broad dimensions should be considered as important potential targets to improve quality of life of this vulnerable population.

Resume Les troubles somatiques fonctionnels sont frequents tant en medecine generale que dans chacune des specialites medicales. Plusieurs axes de traitement ont fait la preuve de leur efficacite. Cependant, leur mise en œuvre peut etre entravee par des difficultes d’adhesion au diagnostic. Des modeles recents issus des sciences cognitives offrent des outils pour eclairer la physiopathologie des troubles somatiques fonctionnels et rendre le diagnostic mieux compris et accepte tant par les patients que par les professionnels impliques. Explicite en termes simples et avec des exemples concrets, le modele cognitif bayesien en particulier met en lumiere les mecanismes qui sous-tendent les symptomes physiques des troubles somatiques fonctionnels et le mode d’action des traitements. Cette approche presente ainsi le double avantage d’etre conforme aux connaissances scientifiques et de favoriser la qualite de la relation de soin.

International audience; Importance:The electronic cigarette (EC) has become popular among smokers who wish to reduce their tobacco use levels or quit smoking, but its effectiveness as a cessation aid is uncertain.Objective:To examine the association of regular EC use with the number of cigarettes smoked per day, smoking cessation among current smokers, and smoking relapse among former smokers.Design, Setting, and Participants:The CONSTANCES (Consultants des Centres d'Examens de Santé) cohort study, based in France, began recruiting participants January 6, 2012, and is currently ongoing. Participants were enrolled in CONSTANCES through 2015, and included 5400 smokers (mean [SD] follow-up of 23.4 [9.3] months) and 2025 former smokers (mean [SD] follow-up of 22.1 [8.6] months) at baseline who quit smoking in 2010, the year in which ECs were introduced in France, or afterward. Analyses were performed from February 8, 2017, to October 15, 2018.Main Outcomes and Measures:The association between EC use and the number of cigarettes smoked during follow-up was studied using mixed regression models. The likelihood of smoking cessation was studied using Poisson regression models with robust sandwich variance estimators. The association between EC use and smoking relapse among former smokers was studied using Cox proportional hazards regression models. All statistical analyses were adjusted for sociodemographic characteristics, duration of follow-up, and smoking characteristics.Results:Among the 5400 daily smokers (2906 women and 2494 men; mean [SD] age, 44.9 [12.4] years), regular EC use was associated with a significantly higher decrease in the number of cigarettes smoked per day compared with daily smokers who did not use ECs (-4.4 [95% CI, -4.8 to -3.9] vs -2.7 [95% CI, -3.1 to -2.4]), as well as a higher adjusted relative risk of smoking cessation (1.67; 95% CI, 1.51-1.84]). At the same time, among the 2025 former smokers (1004 women and 1021 men; mean [SD] age, 43.6 [12.1] years), EC use was associated with an increase in the rate of smoking relapse among former smokers (adjusted hazard ratio, 1.70; 95% CI, 1.25-2.30).Conclusions and Relevance:This study's findings suggest that, among adult smokers, EC use appears to be associated with a decrease in smoking level and an increase in smoking cessation attempts but also with an increase in the level of smoking relapse in the general population after approximately 2 years of follow-up.

Objectives Self-rated health and depressive symptoms have been shown to improve upon retirement. Participants with obesity might benefit more of retirement because of the extra work-related burden they are carrying. The present study aimed to investigate whether the association between retirement and health changes may depend upon obesity in the large French GAZEL occupational cohort during 21 years of follow-up. Methods 17,655 men and women were included in the analyses. Self-rated health was measured on a scale from 1 to 8 with 8 being very bad. Depressive symptoms were measured at four time points by the CES-D score. Mixed models examined the association of self-rated health or depressive symptoms with time (i.e. from −10 years before to +10 years after retirement), retirement, body mass index (BMI), and their interactions. Results Regardless of retirement, BMI was associated with poorer health. Positive BMI by time interactions showed a less favorable time course of both health indicators in the presence versus the absence of obesity (0.024 versus 0.014 and − 0.19 versus −0.07 points per year for self-rated health and depressive symptoms, respectively). However, negative BMI by retirement interactions showed that the improvement of health observed upon retirement was stronger in with the presence versus the absence of obesity (−0.4 versus −0.3 and − 2.42 versus −1.70 points for self-rated health and depressive symptoms, respectively). Conclusion Improvement upon retirement was observed in the presence of obesity and was even higher than in the presence of normal weight and overweight.

International audience; Background: Psychological factors such as hostility and depression have been associated with cardiovascular disease. However, their role in predicting incident cardiac events independently one of another is not clear.Methods: Among 10,304 GAZEL middle-aged workers free of cardiovascular diseases in 1993, 581 incident cardiac events were validated from 1994–2014. Hostile traits (cognitive hostility, behavioral hostility, irritability and negativism) were assessed with the Buss and Durkee Hostility Inventory at baseline. Depressive symptoms were assessed at baseline and every three years with the Center for Epidemiological Studies Depression scale. We used Cox proportional hazards models to calculate hazard ratios (HR) of hostile traits for incident cardiac events adjusting for baseline self-reported socio-demographics and family history of coronary heart diseases (model 1), then additionally for time-dependent depressive symptoms (either as a binary or continuous variable) (model 2) and for yearly self-reported modifiable cardiovascular risk factors (physical activity, smoking, body mass index, diabetes, dyslipidemia and hypertension) (model 3).Results: In Model 1, the only hostile trait associated with incident cardiac events was irritability (HR for one interquartile range: 1.16, 95% confidence interval: 1.02–1.32). This association was no longer statistically significant when further adjusting for depressive symptoms. Depressive symptoms, in turn, remained significant predictors of cardiac events with HRs ranging from 1.40–1.49 (binary).Limitations: Hostility traits were measured only once.Conclusions: Depressive symptoms might explain the association between irritability and cardiac events and should therefore be prioritized in interventions aiming to prevent cardiovascular disease. Further research is needed to identify the mechanisms underlying this association.

Resume Introduction Dans le cadre d’un reperage standardise et systematique utilisant le questionnaire Fast Alcohol Consumption Evaluation (FACE), nos objectifs etaient : – determiner la prevalence du mesusage de l’alcool (MA) parmi les patients admis au service d’accueil des urgences (SAU) de l’Hopital Europeen Georges-Pompidou ; – rechercher les facteurs associes au MA. Methodes Les patients admis entre 9 h et 17 h ont ete inclus durant 7 jours consecutifs en juin 2017. Les variables recueillies etaient l’âge, le sexe, le motif et le jour d’admission, l’existence d’un etat d’ivresse alcoolique aigue, d’un mesusage en benzodiazepines, l’usage de drogues illicites, et la passation du FACE. Un MA etait defini par un score ≥5 pour les hommes et ≥4 pour les femmes. Des analyses descriptives ont calcule la prevalence du MA et des regressions logistiques les risques de MA. Resultats Au total, 190 hommes et 221 femmes ont ete inclus, dont respectivement 31 % et 19 % d’entre eux qui presentaient un MA. Le risque de MA etait positivement associe au sexe masculin, a une admission en week-end et a l’usage de drogues illicites. Il etait negativement associe a l’âge. Le risque de MA n’etait pas significativement different suivant le motif d’admission (traumatologique versus medical). Le risque de MA n’etait pas associe au mesusage en benzodiazepines. Parmi les 100 patients presentant un MA, seulement six avaient ete admis en etat d’ivresse. Conclusion Au SAU, un reperage systematique est indispensable pour identifier les patients qui devraient beneficier d’une intervention breve ou d’une prise en charge specialisee en addictologie.

Since 2005, at least 38 face transplantations have been performed worldwide. Available recommendations on psychological management are based on isolated cases or small case series, either not focused on mental health or with a short follow-up. We propose herein a clinical commentary on psychological and psychiatric outcomes from the follow-up of a prospective single-center cohort of six patients over a period of 3.5 to 9 years. Seven patients received a face transplant between January 2007 and April 2011: two patients with neurofibromatosis, four with self-inflicted ballistic trauma, one with self-immolation. One patient died at 63 days of cerebral sequelae from cardiac arrest in the setting of bacterial infection. The six other patients were routinely evaluated with unstructured psychological interviews up to May 2016 and with the Short Form 36-item health survey and the Mini-International Neuropsychiatric Interview at one year and at the end of the follow-up. Clinically meaningful observations were the following: a history of mental disorders before disfigurement was associated with poor physical and mental outcomes, including poor adherence and one suicide; untreated depression was associated with poor adherence; acceptance of the new face occurred rapidly and without significant distress in all of the patients; fear of transplant rejection was present to some degree in all of the patients and did not substantially differ from other transplantation settings; media exposure may be disturbing but may also have had positive psychological effects on some of the patients. Mental health issues related to chronic rejection and re-transplantation remain to be explored.

Violent suicide attempts, such as jumping from a height, frequently lead to hospitalization in general hospital with high length of stay (LOS). We investigated features associated with LOS in this context.We retrospectively included all patients admitted after suicide attempts by jumping in non-psychiatric wards of a university hospital between 2008 and 2016. Several socio-demographic and clinical data were collected, including psychiatric diagnoses, coded with the International Classification of Diseases-10th Revision. We used general linear models to identify factors associated with LOS.Among 225 patients (125 men; mean age ± sd: 37.5 ± 15.4 years), several clinical factors were independently associated with a longer LOS: number of injuries (β = 8.2 p .001), external fixator (β = 18.1 p = .01), psychotic disorder (β = 14.6 p = .02) and delirium (β = 16.6 p = .005). Admission in psychiatric ward at discharge tended to be associated with lower LOS (β = -15.3 p = .07).In patients admitted in non-psychiatric wards after suicide attempt by jumping, the presence of a psychotic disorder may increase LOS by several days, and indirectly costs of hospitalization, to a similar extent of non-psychiatric factors. The association of transfer in psychiatric ward with lower LOS suggests that the psychiatric disorder might interfere with medical care.