Pathogens have evolved smart strategies to invade hosts and hijack their immune responses. One such strategy is the targeting of the host RhoGTPases by toxins or virulence factors to hijack the ...cytoskeleton dynamic and immune processes. In response to this microbial attack, the host has evolved an elegant strategy to monitor the function of virulence factors and toxins by sensing the abnormal activity of RhoGTPases. This innate immune strategy of sensing bacterial effector targeting RhoGTPase appears to be a bona fide example of effector-triggered immunity (ETI). Here, we review recently discovered mechanisms by which the host can sense the activity of these toxins through NOD and NOD-like receptors (NLRs).
•The prevalence estimate of burnout was 49% and 5% for severe burnout in French physicians•Emergency physicians, junior residents and physicians with high number of night shifts were found at higher ...risk for burnout.•Some specialties like psychiatrists were insufficiently explored and may be targeted in future studies.
Burnout syndrome is the consequence of chronic work-related stress exposure and is 2–3 times higher than in physicians than in other professions. Many studies exploring burnout in French physicians have been published with inconsistent data regarding its prevalence and associated factors.
To assess the prevalence of burnout and associated factors in French physicians in a systematic review and meta-analysis.
Studies assessing the prevalence of French physician's burnout and its three dimensions emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA) were selected in the following databases from 2000 to April 2017: MEDLINE, BIOSIS WEB OF SCIENCE, PASCAL ET FRANCIS, SCIENCES DIRECT, PSYCHinfo, and BDSP. Burnout was defined by one abnormal score in one or more of the 3 dimensions of the MBI scale (EE, DP or PA). Severe burnout was defined by the association of high scores of EE and DP, and low score of PA. High EE was defined by an EE score ≥27. High DP was defined by a score ≥10. Low PA was defined by a score ≤33.
A total of 37 studies and 15,183 French physicians were included in the present meta-analysis. The random effects pooled prevalence estimate was 49% (95% CI 45%–53%, P < 0.001, I2 = 93.1%) for burnout, 5% (95% CI 4–7, P < 0.001, I2 = 92.7%) for severe burnout, 21% (95% CI 19–24, P < 0.001, I2 = 94.7%) for high EE, 29% (95% CI 25–33, P < 0.001, I2 = 96.7%) for high DP, and 29% (95% CI 24–34, P < 0.001, I2 = 97.7%) for low PA. Emergency physicians were found to have a trend to higher rates of burnout (P = 0.051), and significantly more severe burnout compared to other physicians (b = 0.05, seb = 0.02, P = 0.019). Junior residents were found to have higher rates of DP; junior residents, sample size, and monthly number of night shifts were associated with lower PA; and anesthesiologists were found to have lower rates of high EE and high DP.
Burnout is highly prevalent in French physicians. Some recommendations may be suggested to reduce this rate, including reducing the number or duration of night shifts to increase personal accomplishment and targeting emergency physicians and junior residents in priority. Other specialties should be explored in future studies.
This study aims to develop high-performing Machine Learning and Deep Learning models in predicting hospital length of stay (LOS) while enhancing interpretability. We compare performance and ...interpretability of models trained only on structured tabular data with models trained only on unstructured clinical text data, and on mixed data. The structured data was used to train fourteen classical Machine Learning models including advanced ensemble trees, neural networks and k-nearest neighbors. The unstructured data was used to fine-tune a pre-trained Bio Clinical BERT Transformer Deep Learning model. The structured and unstructured data were then merged into a tabular dataset after vectorization of the clinical text and a dimensional reduction through Latent Dirichlet Allocation. The study used the free and publicly available Medical Information Mart for Intensive Care (MIMIC) III database, on the open AutoML Library AutoGluon. Performance is evaluated with respect to two types of random classifiers, used as baselines. The best model from structured data demonstrates high performance (ROC AUC = 0.944, PRC AUC = 0.655) with limited interpretability, where the most important predictors of prolonged LOS are the level of blood urea nitrogen and of platelets. The Transformer model displays a good but lower performance (ROC AUC = 0.842, PRC AUC = 0.375) with a richer array of interpretability by providing more specific in-hospital factors including procedures, conditions, and medical history. The best model trained on mixed data satisfies both a high level of performance (ROC AUC = 0.963, PRC AUC = 0.746) and a much larger scope in interpretability including pathologies of the intestine, the colon, and the blood; infectious diseases, respiratory problems, procedures involving sedation and intubation, and vascular surgery. Our results outperform most of the state-of-the-art models in LOS prediction both in terms of performance and of interpretability. Data fusion between structured and unstructured text data may significantly improve performance and interpretability.
Abstract
Patients with schizophrenia (SCZ) represent a vulnerable population who have been understudied in COVID-19 research. We aimed to establish whether health outcomes and care differed between ...patients with SCZ and patients without a diagnosis of severe mental illness. We conducted a population-based cohort study of all patients with identified COVID-19 and respiratory symptoms who were hospitalized in France between February and June 2020. Cases were patients who had a diagnosis of SCZ. Controls were patients who did not have a diagnosis of severe mental illness. The outcomes were in-hospital mortality and intensive care unit (ICU) admission. A total of 50 750 patients were included, of whom 823 were SCZ patients (1.6%). The SCZ patients had an increased in-hospital mortality (25.6% vs 21.7%; adjusted OR 1.30 95% CI, 1.08–1.56, P = .0093) and a decreased ICU admission rate (23.7% vs 28.4%; adjusted OR, 0.75 95% CI, 0.62–0.91, P = .0062) compared with controls. Significant interactions between SCZ and age for mortality and ICU admission were observed (P = .0006 and P < .0001). SCZ patients between 65 and 80 years had a significantly higher risk of death than controls of the same age (+7.89%). SCZ patients younger than 55 years had more ICU admissions (+13.93%) and SCZ patients between 65 and 80 years and older than 80 years had less ICU admissions than controls of the same age (−15.44% and −5.93%, respectively). Our findings report the existence of disparities in health and health care between SCZ patients and patients without a diagnosis of severe mental illness. These disparities differed according to the age and clinical profile of SCZ patients, suggesting the importance of personalized COVID-19 clinical management and health care strategies before, during, and after hospitalization for reducing health disparities in this vulnerable population.
The Brief Coping Orientation to Problems Experienced (Brief COPE) inventory is the most usual measure to identify the nature of coping strategies implemented by individuals and explore 14 coping ...strategies. The availability of a structure with fewer factors rather than the initial 14-factor structure may be of interest for both healthcare professionals and researchers. We report the validation process of a 4-factor structure of the French version of the Brief COPE in a French sample of individuals facing a singular life event, such as cancer, including patients and their caregivers.
The cross-sectional study included cancer patients and their caregivers. Self-administered data were collected including: socio-demographic (age, gender, marital status, employment status, and education level), coping strategies using the French version of the Brief COPE, quality of life (QoL) using the French version of the short form health survey questionnaire (SF36). Construct validity, internal consistency, reliability, and external validity were tested.
The sample included 398 individuals. The principal component factor analysis identified a 4-factor structure. The dimensions were labeled according to their constitutive items: social support (8 items), problem solving (4), avoidance (10), and positive thinking (6). The 4-factor structure was supported by different theoretical models of coping and showed satisfactory psychometric properties.
The 4-factor structure of the French version of the Brief COPE, validated in a sample of individuals facing a singular stressful event, including cancer patients and their caregivers, makes the instrument easier to use both in clinical practice and clinical research.
In the last decade, a major dogma in the field of immunology has been called into question by the identification of a cell autonomous innate immune memory. This innate immune memory (also named ...trained immunity) was found to be mostly carried by innate immune cells and to be characterized by an exacerbated inflammatory response with a heightened expression of proinflammatory cytokines, including TNF-α, IL-6 and IL-1β. Unlike the vast majority of cytokines, IL-1β is produced as a proform (pro-IL-1β) and requires a proteolytic cleavage to exert its biological action. This cleavage takes place mainly within complex molecular platforms named inflammasomes. These platforms are assembled upon both the infectious or sterile activation of NOD-like receptors (NLRs), thereby allowing for the recruitment and activation of caspases and the subsequent maturation of pro-IL-1β into IL-1β. The NLRP3 inflammasome has recently been implicated both in western diet-induced trained immunity, and in the detection of microbial virulence factors (effector-triggered immunity (ETI)). Here, we will attempt to link these two immune processes and provide arguments to hypothesize the existence of trained immunity triggered by microbial virulence factors (effector-triggered trained immunity (ETTI)).
Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of ...inflammation in schizophrenia and their application in daily practice.
This review was based on the most recent meta-analyses and randomized controlled trials.
The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia.
The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.
Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, ...constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case–control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69,
p
< 0.01,
I
2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19,
p
< 0.01,
I
2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.
Abstract
Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never ...been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized scale or with structured interviews were included. The Medline, Web of Science, PsycINFO, and Google Scholar databases were searched. Using random effects models, we calculated the pooled estimate of the prevalence of SZ-MDD. We used meta-regression and subgroup analyses to evaluate the potential moderators of the prevalence estimates, and we used the leave-one-out method for sensitivity analyses. Of the 5633 potentially eligible studies identified, 18 studies (n = 6140 SZ stabilized outpatients) were retrieved in the systematic review and included in the meta-analysis. The pooled estimate of the prevalence of SZ-MDD was 32.6% (95% CI: 27.9–37.6); there was high heterogeneity (I2 = 92.6%), and Egger’s test did not reveal publication bias (P = .122). The following factors were found to be sources of heterogeneity: publication in or after 2015, the inclusion of patients from larger studies, the assessment tools, the inclusion of patients with substance use disorder or somatic chronic diseases, age, education level, the lifetime number of hospitalizations, and antidepressant use. Two-thirds of the extracted variables could not be explored due to an insufficient amount of published data. The prevalence of MDD is high among SZ individuals. Healthcare providers and public health officials should have an increased awareness of the burden of SZ-MDD.
Background. Fasting interventions have shown effectiveness in alleviating stress, anxiety and depressive symptoms. However, no quantitative analysis has been carried out thus far. The objective was ...to determine the effectiveness of fasting interventions on stress, anxiety and depression and if these interventions were associated with increased or decreased fatigue/energy. Methods. Overall, 11 studies and 1436 participants were included in the quantitative analyses. Results. After limiting analyses to randomized controlled trials with low risk of bias, we found that fasting groups had lower anxiety (b = −0.508, p = 0.038), depression levels (b= −0.281, p = 0.012) and body mass index compared to controls without increased fatigue. There was no publication bias and no heterogeneity for these results. These interventions were safe, even in patients with type 2 diabetes. Conclusions. These results should be taken with a caveat. These results are preliminary and encouraging and fasting appears to be a safe intervention. Data are not sufficient to recommend one fasting intervention more than the others. No study was carried out in psychiatric populations and further trials should be carried out in these populations that may be good candidates for fasting interventions.
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