Hôpital Corentin-Celton

Secondary prevention through comprehensive cardiac rehabilitation has been recognized as the most cost-effective intervention to ensure favourable outcomes across a wide spectrum of cardiovascular disease, reducing cardiovascular mortality, morbidity and disability, and to increase quality of life. The delivery of a comprehensive and 'modern' cardiac rehabilitation programme is mandatory both in the residential and the out-patient setting to ensure expected outcomes. The present position paper aims to update the practical recommendations on the core components and goals of cardiac rehabilitation intervention in different cardiovascular conditions, in order to assist the whole cardiac rehabilitation staff in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and patients in the recognition of the positive nature of cardiac rehabilitation. Starting from the previous position paper published in 2010, this updated document maintains a disease-oriented approach, presenting both well-established and more controversial aspects. Particularly for implementation of the exercise programme, advances in different training modalities were added and new challenging populations were considered. A general table applicable to all cardiovascular conditions and specific tables for each clinical condition have been created for routine practice.

Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment.

Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel-based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self-reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings.

Abstract Background: Apathy is a very common behavioural and psychological symptom across brain disorders. In the last decade, there have been considerable advances in research on apathy and motivation. It is thus important to revise the apathy diagnostic criteria published in 2009. The main objectives were to: a) revise the definition of apathy; b) update the list of apathy dimensions; c) operationalise the diagnostic criteria; and d) suggest appropriate assessment tools including new technologies. Methods: The expert panel (N = 23) included researchers and health care professionals working on brain disorders and apathy, a representative of a regulatory body, and a representative of the pharmaceutical industry. The revised diagnostic criteria for apathy were developed in a two-step process. First, following the standard Delphi methodology, the experts were asked to answer questions via web-survey in two rounds. Second, all the collected information was discussed on the occasion of the 26th European Congress of Psychiatry held in Nice (France). Results: Apathy was defined as a quantitative reduction of goal-directed activity in comparison to the patient’s previous level of functioning (criterion A). Symptoms must persist for at least four weeks, and affect at least two of the three apathy dimensions (behaviour/cognition; emotion; social interaction; criterion B). Apathy should cause identifiable functional impairments (criterion C), and should not be fully explained by other factors, such as effects of a substance or major changes in the patient’s environment (Criterion D). Table 1 Apathy diagnostic criteria 2018. CRITERION A: A quantitative reduction of goal-directed activity either in behavioral, cognitive, emotional or social dimensions in comparison to the patient’s previous level of functioning in these areas. These changes may be reported by the patient himself/herself or by observation of others. CRITERION B: The presence of at least 2 of the 3 following dimensions for a period of at least four weeks and present most of the time B1. BEHAVIOUR & COGNITION Loss of, or diminished, goal-directed behaviour or cognitive activity as evidenced by at least one of the following: General level of activity: the patient has a reduced level of activity either at home or work, makes less effort to initiate or accomplish tasks spontaneously, or needs to be prompted to perform them. Persistence of activity: He/she is less persistent in maintaining an activity or conversation, finding solutions to problems or thinking of alternative ways to accomplish them if they become difficult. Making choices: He/she has less interest or takes longer to make choices when different alternatives exist (e.g., selecting TV programs, preparing meals, choosing from a menu, etc.) Interest in external issue: He/she has less interest in or reacts less to news, either good or bad, or has less interest in doing new things Personal wellbeing: He/she is less interested in his/her own health and wellbeing or personal image (general appearance, grooming, clothes, etc.). B2. EMOTION Loss of, or diminished, emotion as evidenced by at least one of the following: Spontaneous emotions: the patient shows less spontaneous (self-generated) emotions regarding their own affairs, or appears less interested in events that should matter to him/her or to people that he/she knows well. Emotional reactions to environment: He/she expresses less emotional reaction in response to positive or negative events in his/her environment that affect him/her or people he/she knows well (e.g., when things go well or bad, responding to jokes, or events on a TV program or a movie, or when disturbed or prompted to do things he/she would prefer not to do). Impact on others: He/she is less concerned about the impact of his/her actions or feelings on the people around him/her. Empathy: He/she shows less empathy to the emotions or feelings of others (e.g., becoming happy or sad when someone is happy or sad, or being moved when others need help). Verbal or physical expressions: He/she shows less verbal or physical reactions that reveal his/her emotional states. B3. SOCIAL INTERACTION Loss of, or diminished engagement in social interaction as evidenced by at least one of the following: Spontaneous social initiative: the patient takes less initiative in spontaneously proposing social or leisure activities to family or others. Environmentally stimulated social interaction: He/she participates less, or is less comfortable or more indifferent to social or leisure activities suggested by people around him/her. Relationship with family members: He/she shows less interest in family members (e.g., to know what is happening to them, to meet them or make arrangements to contact them). Verbal interaction: He/she is less likely to initiate a conversation, or he/she withdraws soon from it Homebound : He /She prefer to stays at home more frequently or longer than usual and shows less interest in getting out to meet people. CRITERION C These symptoms (A - B) cause clinically significant impairment in personal, social, occupational, or other important areas of functioning. CRITERION D The symptoms (A - B) are not exclusively explained or due to physical disabilities (e.g. blindness and loss of hearing), to motor disabilities, to a diminished level of consciousness, to the direct physiological effects of a substance (e.g. drug of abuse, medication), or to major changes in the patient’s environment. Conclusions: The new diagnostic criteria for apathy provide a clinical and scientific framework to increase the validity of apathy as a clinical construct. This should also help to pave the path for apathy in brain disorders to be an interventional target.

A proper determination of the exercise intensity is important for the rehabilitation of patients with cardiovascular disease (CVD) since it affects the effectiveness and medical safety of exercise training. In 2013, the European Association of Preventive Cardiology (EAPC), together with the American Association of Cardiovascular and Pulmonary Rehabilitation and the Canadian Association of Cardiac Rehabilitation, published a position statement on aerobic exercise intensity assessment and prescription in cardiovascular rehabilitation (CR). Since this publication, many subsequent papers were published concerning the determination of the exercise intensity in CR, in which some controversies were revealed and some of the commonly applied concepts were further refined. Moreover, how to determine the exercise intensity during resistance training was not covered in this position paper. In light of these new findings, an update on how to determine the exercise intensity for patients with CVD is mandatory, both for aerobic and resistance exercises. In this EAPC position paper, it will be explained in detail which objective and subjective methods for CR exercise intensity determination exist for aerobic and resistance training, together with their (dis)advantages and practical applications.

Importance: After an infection by SARS-CoV-2, many patients present with persistent physical symptoms that may impair their quality of life. Beliefs regarding the causes of these symptoms may influence their perception and promote maladaptive health behaviors. Objective: To examine the associations of self-reported COVID-19 infection and SARS-CoV-2 serology test results with persistent physical symptoms (eg, fatigue, breathlessness, or impaired attention) in the general population during the COVID-19 pandemic. Design, Setting, and Participants: Participants in this cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, an enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Between December 2020 and January 2021, the participants reported whether they believed they had experienced COVID-19 infection and had physical symptoms during the previous 4 weeks that had persisted for at least 8 weeks. Participants who reported having an initial COVID-19 infection only after completing the serology test were excluded. Main Outcomes and Measures: Logistic regressions for each persistent symptom as the outcome were computed in models including both self-reported COVID-19 infection and serology test results and adjusting for age, sex, income, and educational level. Results: Of 35 852 volunteers invited to participate in the study, 26 823 (74.8%) with complete data were included in the present study (mean [SD] age, 49.4 [12.9] years; 13 731 women [51.2%]). Self-reported infection was positively associated with persistent physical symptoms, with odds ratios ranging from 1.39 (95% CI, 1.03-1.86) to 16.37 (95% CI, 10.21-26.24) except for hearing impairment (odds ratio, 1.45; 95% CI, 0.82-2.55) and sleep problems (odds ratio, 1.14; 95% CI, 0.89-1.46). A serology test result positive for SARS-COV-2 was positively associated only with persistent anosmia (odds ratio, 2.72; 95% CI, 1.66-4.46), even when restricting the analyses to participants who attributed their symptoms to COVID-19 infection. Further adjusting for self-rated health or depressive symptoms yielded similar results. There was no significant interaction between belief and serology test results. Conclusions and Relevance: The findings of this cross-sectional analysis of a large, population-based French cohort suggest that persistent physical symptoms after COVID-19 infection may be associated more with the belief in having been infected with SARS-CoV-2 than with having laboratory-confirmed COVID-19 infection. Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus. A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to "long COVID."

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Frailty is a geriatric syndrome characterised by a vulnerability status associated with declining function of multiple physiological systems and loss of physiological reserves. Two main models of frailty have been advanced: the phenotypic model (primary frailty) or deficits accumulation model (secondary frailty), and different instruments have been proposed and validated to measure frailty. However measured, frailty correlates to medical outcomes in the elderly, and has been shown to have prognostic value for patients in different clinical settings, such as in patients with coronary artery disease, after cardiac surgery or transvalvular aortic valve replacement, in patients with chronic heart failure or after left ventricular assist device implantation. The prevalence, clinical and prognostic relevance of frailty in a cardiac rehabilitation setting has not yet been well characterised, despite the increasing frequency of elderly patients in cardiac rehabilitation, where frailty is likely to influence the onset, type and intensity of the exercise training programme and the design of tailored rehabilitative interventions for these patients. Therefore, we need to start looking for frailty in elderly patients entering cardiac rehabilitation programmes and become more familiar with some of the tools to recognise and evaluate the severity of this condition. Furthermore, we need to better understand whether exercise-based cardiac rehabilitation may change the course and the prognosis of frailty in cardiovascular patients.

BACKGROUND: There have been few randomized controlled trials evaluating nonoperative treatment of proximal humeral fractures. To investigate shortening the period of dependence, we assessed the feasibility and efficacy of early mobilization of the shoulder (within three days after the fracture) in comparison with those of conventional three-week immobilization followed by physiotherapy. METHODS: We randomly assigned seventy-four patients with an impacted proximal humeral fracture to receive early passive mobilization or conventional treatment. The primary outcome was the overall shoulder functional status (as measured with the Constant score) at three months. The secondary outcomes were the Constant score at six weeks and at six months, the change in pain (on a visual analog scale), and the active and passive range of motion. RESULTS: At three months and at six weeks, the early mobilization group had a significantly better Constant score than did the conventional-treatment group (between-group difference, 9.9 [95% confidence interval, 1.9 to 17.8] [p = 0.02] and 10.1 [95% confidence interval, 2.0 to 18.1] [p = 0.02], respectively) and better active mobility in forward elevation (between-group difference, 12.0 [95% confidence interval, 1.7 to 22.4] [p = 0.02] and 28.1 [95% confidence interval, 7.1 to 49.1] [p = 0.01], respectively). At three months, the early mobilization group had significantly reduced pain compared with the conventional-treatment group (between-group difference, 15.7 [95% confidence interval, 0.52 to 30.8] [p = 0.04]). No complications in displacement or nonhealing were noted. CONCLUSIONS: Early mobilization for impacted nonoperatively treated proximal humeral fractures is safe and is more effective for quickly restoring the physical capability and performance of the injured arm than is conventional immobilization followed by physiotherapy.

BACKGROUND: Research on the impact of the continuity of care (COC) on health outcomes in patients with mental illness is limited. This observational study examined whether the longitudinal COC is associated with a decreased likelihood of death among patients with mental disorders in the French general population. METHOD: Data were derived from the French National Health Insurance (NHI) reimbursement database. Patients with any mental disorder who visited a psychiatrist at least twice within 6 months were included. The primary endpoint was death by all causes. We measured longitudinal COC with a psychiatrist twice a year between 2007 and 2010, using the COC index developed by Bice and Boxerman. The COC index was analysed as a time-dependent variable in a survival analysis after adjustments for age, gender and stratifying on comorbidities and social status. RESULTS: Among 14,515 patients visiting a psychiatrist at least twice in 6 months and tracked over 3 years, likelihood of death was significantly lower in patients with higher continuity of care (hazard ratio for an increase in 0.1 of continuity, adjusted for age, sex, and stratified on comorbidities and social status: 0.83 [0.83-0.83]), particularly in those with bipolar disorder, major depressive disorder and schizophrenia. CONCLUSION: Improving longitudinal continuity of care in mental health care may contribute to substantially decrease mortality.

Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many clinically approved medications functionally inhibit ASM and are called FIASMAs (functional inhibitors of acid sphingomyelinase). The FIASMA fluvoxamine showed beneficial effects on COVID-19 in a randomized prospective study and a prospective open-label real-world study. Retrospective and observational studies showed favorable effects of FIASMA antidepressants including fluoxetine, and the FIASMA hydroxyzine on the course of COVID-19. The ASM/ceramide system provides a framework for a better understanding of the infection of cells by SARS-CoV-2 and the clinical, antiviral, and anti-inflammatory effects of functional inhibitors of ASM. This framework also supports the development of new drugs or the repurposing of "old" drugs against COVID-19.

BACKGROUND: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). METHOD: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled. RESULTS: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27-33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30-2.63), ADL score <4 (OR 1.84; 95% CI 1.25-2.70), asthenia (OR 1.59; 95% CI 1.08-2.32), quick Sequential Organ Failure Assessment score ≥2 (OR 2.63; 95% CI 1.64-4.22), and specific COVID-19 anomalies on chest computerized tomography (OR 2.60; 95% CI 1.07-6.46). CONCLUSIONS: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.

C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019.

BACKGROUND: Some prognostic markers of venous leg ulcer (VLU) healing have been evaluated, mostly in retrospective studies. OBJECTIVES: To identify which clinical characteristics, among those known as possible prognostic factors of VLU healing, and which VLU-associated sociodemographic and psychological factors, are associated with complete healing at week 24 (W24). METHODS: A prospective, multicentre, cohort study was conducted in 22 French dermatology departments between September 2003 and December 2007. The end point was comparison between healed and nonhealed VLUs at W24, for patient clinical and biological characteristics; psychological, cognitive and social assessments; affected leg inclusion characteristics; venous insufficiency treatment and percentage of initial wound area reduction during follow-up. RESULTS: In total, 104 VLUs in 104 patients were included; 94 were analysed. The mean VLU area and duration were 36.8 ± 55.5 cm2 and 24.8 ± 45.7 months, respectively. At W24, 41/94 VLUs were healed. Univariate analysis significantly associated complete healing with superficial venous surgery (P = 0.001), adherence to compression therapy at W4 (P = 0.03) and W24 (P = 0.01), ankle-joint ankylosis (P = 0.01) and mean percentage of VLU area reduction at W4 (P = 0.04). Multivariate analysis retained superficial venous surgery during follow-up [odds ratio (OR) 8.4, 95% confidence interval (CI) 1.9-48.2] and percentage reduction of the VLU area at W4 (OR 1.6, 95% CI 1.0-2.14) as being independently associated with healing. CONCLUSIONS: These results indicate that complete healing of long-standing, large VLUs is independently associated with ablation of the incompetent superficial vein and percentage of wound area reduction after the first 4 weeks of treatment.

In the past few years, there has been increasing interest in the measurement of thiols, glutathione in particular, as indicators of oxidative stress. The reduced glutathione/oxidized glutathione ratio (GSH/GSSG) is used to evaluate oxidative stress status in biological systems, and alterations of this ratio have been demonstrated in aging, cancer, HIV replication, and cardiovascular diseases (1)(2)(3)(4)(5). Surprisingly, glutathione is usually studied in plasma, which contains only 0.5% of the blood content, whereas erythrocytes contain 99.5%. We were interested in direct measurement of GSH and GSSG in whole blood samples to evaluate overall glutathione status. Numerous methods are available for measuring GSH and GSSG (6), but few of these are suitable for direct analysis in routine use. HPLC is the most widely used, but it requires a long sample preparation with pre- or postcolumn derivatization (7)(8) or a special apparatus for electrochemical detection (1)(9). Alternative methods based on GSH conjugation with a chromophore or a fluorophore have been used, but they need GSSG calculation from total glutathione measured after reduction of GSSG (10)(11). Capillary zone electrophoresis (CZE) coupled with laser-induced fluorescence has been proposed recently (12). The separation of GSH and GSSG by CZE with direct ultraviolet detection in tissues and mitochondria (13)(14) and by micellar electrokinetic capillary electrophoresis in plasma (15) has also been reported. The aim of the present work was to develop and validate a rapid CZE method suitable for a direct measurement of GSH and GSSG in whole blood. Moreover, we describe the distribution of blood GSH and GSSG concentrations in a healthy adult population and in elderly subjects. All chemicals used were of analytical-reagent grade. bis-Tris, boric acid, GSH, and GSSG were obtained from Sigma Chemical, and metaphosphoric acid was …

Venous leg ulcers (VLUs) are the most prevalent chronic wounds in western countries with a heavy socioeconomic impact. Compression therapy is the etiologic treatment of VLU but until now no wound dressing has been shown to be more effective than another. The aim of this study was to assess the efficacy of a new dressing in the management of VLU. Adult patients presenting a noninfected VLU and receiving effective compression therapy were enrolled in this randomized, controlled, double-blind trial. The VLUs were assessed every 2 weeks for 8 weeks. The primary study outcome was the relative Wound Area Reduction (WAR, in %), and the secondary objectives were absolute WAR, healing rate, and percentage of wounds with >40% surface area reduction. One hundred eighty-seven patients were randomly allocated to treatment groups. Median WAR was 58.3% in the Lipido-Colloid Technology-Nano-OligoSaccharide Factor (TLC-NOSF) dressing group (test group) and 31.6% in the TLC dressing group (control group) (difference: -26.7%; 95% confidence interval: -38.3 to -15.1%; p = 0.002). All other efficacy outcomes were also significant in favor of the TLC-NOSF dressing group. Clinical outcomes for patients treated with the new dressing are superior to those patients treated with the TLC dressing (without NOSF compound), suggesting a strong promotion of the VLU healing process.

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

BACKGROUND: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. METHODS: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. RESULTS: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. CONCLUSIONS: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

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Despite the severity of the loss of a parent and the frequency of parental divorce, few studies compared their impact on mental health in the general adult population. The aim of this study was to estimate the prevalence, sociodemographic correlates, and psychiatric comorbidity of parental loss and parental divorce during childhood and adolescence. Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of US adults (n = 43,093). Of the 43,093 participants, parental divorce during childhood or adolescence was reported by 5776 participants, whereas 3377 experienced parental death during childhood or adolescence. Participants reporting a history of parental divorce present a significantly higher prevalence of psychiatric disorders, particularly alcohol and drug use disorders compared with control subjects. While participants experiencing the death of a parent reported a poorer overall health, the prevalence of psychiatric disorder after 17 years of age was not significantly higher than that of the control subjects.