Delayed school progression and mental health problems in adolescence:A population-based study in 10,803 adolescents

Background Accumulating evidence suggests that several adult mental disorders, particularly psychoses, are preceded by impairments in cognitive function, reflected in scholastic underachievement. This study investigates the association between scholastic underachievement and general mental health problems in adolescence, using delay in school progression as a marker of poor scholastic performance.MethodCross-sectional secondary school survey comprising 10,803 adolescents. Participants completed the Strengths and Difficulties Questionnaire (SDQ) to assess mental health problems. The association of delayed school progression with the SDQ was investigated using logistic regression with SDQ as outcome and delayed school progression as primary exposure of interest while adjusting for socio-demographic characteristics, adverse life events, school-related factors, risk taking behaviour, healthy lifestyle and physical health.ResultsUnadjusted analysis showed an association between delayed school progression and total mental health problems (OR 1.83, 95% CI 1.27 - 2.63) in adolescents. After adjusting for other risk factors (socio-demographic factors and life events) in a logistic regression model the association between delayed school progression en mental health problems was attenuated (OR 1.33, 95% CI 0.86 - 2.05).ConclusionDelayed school progression is associated with general mental health problems in adolescence, but this relationship is heavily confounded by other factors. A causal relationship between impaired cognitive function such as poor scholastic performance and general mental health at adolescence is less likely and delayed school progression may merely be considered an indicator of risk for mental health problems.</p

A prescription support-tool for chronic management of oral antithrombotic combinations in adults based on a systematic review of international guidelines

International audienceBACKGROUND: Oral antithrombotic (AT) drugs, which include antiplatelet and anticoagulant therapies, are widely implicated in serious preventable bleeding events. Avoiding inappropriate oral AT combinations is a major concern. Numerous practical guidelines have been released; a document to enhance prescriptions of oral AT combinations for adults would be of great help.OBJECTIVE: To synthesize guidelines on the prescription of oral AT combinations in adults and to create a prescription support-tool for clinicians about chronic management (≥ one month) of oral AT combinations.METHODS: A systematic review of guidelines published between January 2012 and April 2017, in English or in French, from Trip database, Guideline International Network and PubMed, dealing with the prescription of oral ATs in adults was conducted. In-hospital management of ATs, bridging therapy and switches of ATs were not considered. Some specific topics requiring specialized follow-up (cancer, auto-immune disease, haemophilia, HIV, paediatrics and pregnancy) were excluded. Last update was made in November 2018.RESULTS: A total of 885 guidelines were identified and 70 met the eligibility criteria. A prescription support-tool summarizing medical conditions requiring chronic management of oral AT combinations in adults with drug types, dosage and duration, on a double-sided page, was provided and tested by an external committee of physicians. The lack of specific guidelines for old people (age 75 years and older) is questioned considering the specific vulnerability of this age group to serious bleedings.CONCLUSIONS:Recommendations on prescriptions about chronic management of oral AT combinations in adults were mainly consensual but dispersed in numerous guidelines according to the medical indication. We provide a prescription support-tool for clinicians. Further studies are needed to assess the impact of this tool on appropriate prescribing and the prevention of serious adverse drug events

Identifying individual and organizational predictors of accidental exposure to blood (AEB) among hospital healthcare workers: A longitudinal study

International audienceBackground: Accidental exposure to blood (AEB) poses a risk of bloodborne infections for healthcare workers (HCWs) during hospital activities. In this study, we identified individual behavioral and organizational predictors of AEB among HCWs. Methods: The study was a prospective, 1-year follow-up cohort study conducted in university hospitals in Paris, France. Data were collected from the Stress at Work and Infectious Risk in Patients and Caregivers (STRIPPS) study. Eligible participants included nurses, nursing assistants, midwives, and physicians from 32 randomly selected wards in 4 hospitals. AEB occurrences were reported at baseline, 4 months, 8 months, and 12 months, and descriptive statistical and multilevel risk-factor analyses were performed. Results: The study included 730 HCWs from 32 wards, predominantly nurses (52.6%), nursing assistants (41.1%), physicians (4.8%), and midwives (1.5%). The incidence rate of AEB remained stable across the 4 visits. The multilevel longitudinal analysis identified several significant predictors of AEB occurrence. Individual-level predictors included younger age, occupation as nurses or midwives, irregular work schedule, rotating shifts, and lack of support from supervisors. The use of external nurses was the most significant ward-level predictor associated with AEB occurrence. Conclusions: AEBs among HCWs are strongly associated with organizational predictors, highlighting the importance of complementing infection control policies with improved staff management and targeted training. This approach can help reduce AEB occurrences and enhance workplace safety for HCWs

A multilevel approach to individual and organizational predictors of stress and fatigue among healthcare workers of a university hospital: A longitudinal study

This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.Objective Healthcare workers are at high risk of experiencing stress and fatigue due to the demands of their work within hospitals. Improving their physical and mental health and in turn, the quality and safety of care, requires considering factors at both individual and organizational levels. Using a multi-center prospective cohort, this study aims to identify the individual and organizational predictors of stress and fatigue of healthcare workers in several wards from university hospitals. Methods Our cohort consist of 695 healthcare workers from 32 hospital wards drawn at random within four volunteer hospital centers in Paris-area. Three-level longitudinal analyses, accounting for repeated measures (level 1) across participants (level 2) nested within wards (level 3) and adjusted for relevant fixed and time varying confounders were performed. Results At baseline, the sample was composed by 384 registered nurses, 300 auxiliary nurses and 11 midwives. According to the 3-level longitudinal models, some predictors were found in common for both stress and fatigue (low support from the hierarchy, low safety culture, overcommitment at work, presenteeism while sick…). However, specific predictors for high level of stress (negative life events, low support from the colleagues and high frequency of break cancellation) and fatigue (commuting duration, frequent use of interim staff in the ward…) were also found. Conclusion Our results may help identify at-risk healthcare workers and wards, where interventions to reduce stress and fatigue should be focused. These interventions could include manager training to favor better staff support and overall safety culture of healthcare workers. 1. What is already known about this subject? Healthcare workers have high levels of perceived stress and fatigue, particularly in medical fields highly exposed to infectious risks. High occupational stress and fatigue can negatively affect healthcare workers behaviors in terms of absenteeism, and ultimately intention to leave as well as quality of care. Individual and organizational differences contribute to different perceptions and consequences of occupational stress and fatigue in healthcare workers. 2. What are the new findings? The ward-level environment significantly influences the stress and fatigue of healthcare workers, in addition to individual factors and time variations. Hierarchy providing low support and with low safety culture, work overinvestment, presenteeism while sick, and working in smaller wards were identified as predictors of both high stress and fatigue of healthcare workers. Negative life events (whether personal or professional), low support from the colleagues and high frequency of break cancellation are specific predictors of high level of stress. While commuting duration, frequent use of interim staff and working in a medical ward were associated with high level of fatigue. 3. How might this impact on policy or clinical practice in the foreseeable future? In this study, we can identify some areas for improvement to better prevent stress and fatigue for healthcare workers. High stress and fatigue can be reduced through mutual and specific organizational intervention strategies

Multilevel approach to individual and organisational predictors of stress and fatigue among healthcare workers of a university hospital: a longitudinal study

International audienceObjective Healthcare workers (HCWs) are at high risk of experiencing stress and fatigue due to the demands of their work within hospitals. Improving their physical and mental health and, in turn, the quality and safety of care requires considering factors at both individual and organisational/ward levels. Using a multicentre prospective cohort, this study aims to identify the individual and organisational predictors of stress and fatigue of HCWs in several wards from university hospitals. Methods Our cohort consists of 695 HCWs from 32 hospital wards drawn at random within four volunteer hospital centres in Paris-area. Three-level longitudinal analyses, accounting for repeated measures (level 1) across participants (level 2) nested within wards (level 3) and adjusted for relevant fixed and time-varying confounders, were performed. Results At baseline, the sample was composed by 384 registered nurses, 300 auxiliary nurses and 11 midwives. According to the three-level longitudinal models, some predictors were found in common for both stress and fatigue (low social support from supervisors, work overcommitment, sickness presenteeism and number of beds per ward). However, specific predictors for high level of stress (negative life events, low social support from colleagues and breaks frequently cancelled due to work overload) and fatigue (longer commuting duration, frequent use of interim staff in the ward) were also found. Conclusion Our results may help identify at-risk HCWs and wards, where interventions to reduce stress and fatigue should be focused. These interventions could include manager training to favour better staff support and overall safety culture of HCWs

AACR calls on congress to take immediate action against COVID-19 and protect patients with cancer during the pandemic

On March 30, 2020, the AACR Board of Directors provided a letter to the U.S. Congressional leadership on behalf of its members in response to the COVID-19 public health emergency.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer

Background Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.Methods In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included 18F-BMS-986192 (PD-L1) PET and 18F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology.Results Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1.Conclusion Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations

Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications

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Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND

Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

147siIntroduction Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. Discussion Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.partially_openopenVergallo A.; Bun R.-S.; Toschi N.; Baldacci F.; Zetterberg H.; Blennow K.; Cavedo E.; Lamari F.; Habert M.-O.; Dubois B.; Floris R.; Garaci F.; Lista S.; Hampel H.; Audrain C.; Auffret A.; Bakardjian H.; Baldacci F.; Batrancourt B.; Benakki I.; Benali H.; Bertin H.; Bertrand A.; Boukadida L.; Cacciamani F.; Causse V.; Cavedo E.; Cherif Touil S.; Chiesa P.A.; Colliot O.; Dalla Barba G.; Depaulis M.; Dos Santos A.; Dubois B.; Dubois M.; Epelbaum S.; Fontaine B.; Francisque H.; Gagliardi G.; Genin A.; Genthon R.; Glasman P.; Gombert F.; Habert M.O.; Hampel H.; Hewa H.; Houot M.; Jungalee N.; Kas A.; Kilani M.; La Corte V.; Le Roy F.; Lehericy S.; Letondor C.; Levy M.; Lista S.; Lowrey M.; Ly J.; Makiese O.; Masetti I.; Mendes A.; Metzinger C.; Michon A.; Mochel F.; Nait Arab R.; Nyasse F.; Perrin C.; Poirier F.; Poisson C.; Potier M.C.; Ratovohery S.; Revillon M.; Rojkova K.; Santos-Andrade K.; Schindler R.; Servera M.C.; Seux L.; Simon V.; Skovronsky D.; Thiebaut M.; Uspenskaya O.; Vlaincu M.; Aguilar L.F.; Babiloni C.; Baldacci F.; Benda N.; Black K.L.; Bokde A.L.W.; Bonuccelli U.; Broich K.; Bun R.S.; Cacciola F.; Castrillo J.; Cavedo E.; Ceravolo R.; Chiesa P.A.; Colliot O.; Coman C.M.; Corvol J.C.; Cuello A.C.; Cummings J.L.; Depypere H.; Dubois B.; Duggento A.; Durrleman S.; Escott-Price V.; Federoff H.; Ferretti M.T.; Fiandaca M.; Frank R.A.; Garaci F.; Genthon R.; George N.; Giorgi F.S.; Graziani M.; Haberkamp M.; Habert M.O.; Hampel H.; Herholz K.; Karran E.; Kim S.H.; Koronyo Y.; Koronyo-Hamaoui M.; Lamari F.; Langevin T.; Lehericy S.; Lista S.; Lorenceau J.; Mapstone M.; Neri C.; Nistico R.; Nyasse-Messene F.; O'Bryant S.E.; Perry G.; Ritchie C.; Rojkova K.; Rossi S.; Santarnecchi E.; Schneider L.S.; Sporns O.; Toschi N.; Verdooner S.R.; Vergallo A.; Villain N.; Welikovitch L.; Woodcock J.; Younesi E.Vergallo, A.; Bun, R. -S.; Toschi, N.; Baldacci, F.; Zetterberg, H.; Blennow, K.; Cavedo, E.; Lamari, F.; Habert, M. -O.; Dubois, B.; Floris, R.; Garaci, F.; Lista, S.; Hampel, H.; Audrain, C.; Auffret, A.; Bakardjian, H.; Baldacci, F.; Batrancourt, B.; Benakki, I.; Benali, H.; Bertin, H.; Bertrand, A.; Boukadida, L.; Cacciamani, F.; Causse, V.; Cavedo, E.; Cherif Touil, S.; Chiesa, P. A.; Colliot, O.; Dalla Barba, G.; Depaulis, M.; Dos Santos, A.; Dubois, B.; Dubois, M.; Epelbaum, S.; Fontaine, B.; Francisque, H.; Gagliardi, G.; Genin, A.; Genthon, R.; Glasman, P.; Gombert, F.; Habert, M. O.; Hampel, H.; Hewa, H.; Houot, M.; Jungalee, N.; Kas, A.; Kilani, M.; La Corte, V.; Le Roy, F.; Lehericy, S.; Letondor, C.; Levy, M.; Lista, S.; Lowrey, M.; Ly, J.; Makiese, O.; Masetti, I.; Mendes, A.; Metzinger, C.; Michon, A.; Mochel, F.; Nait Arab, R.; Nyasse, F.; Perrin, C.; Poirier, F.; Poisson, C.; Potier, M. C.; Ratovohery, S.; Revillon, M.; Rojkova, K.; Santos-Andrade, K.; Schindler, R.; Servera, M. C.; Seux, L.; Simon, V.; Skovronsky, D.; Thiebaut, M.; Uspenskaya, O.; Vlaincu, M.; Aguilar, L. F.; Babiloni, C.; Baldacci, F.; Benda, N.; Black, K. L.; Bokde, A. L. W.; Bonuccelli, U.; Broich, K.; Bun, R. S.; Cacciola, F.; Castrillo, J.; Cavedo, E.; Ceravolo, R.; Chiesa, P. A.; Colliot, O.; Coman, C. M.; Corvol, J. C.; Cuello, A. C.; Cummings, J. L.; Depypere, H.; Dubois, B.; Duggento, A.; Durrleman, S.; Escott-Price, V.; Federoff, H.; Ferretti, M. T.; Fiandaca, M.; Frank, R. A.; Garaci, F.; Genthon, R.; George, N.; Giorgi, F. S.; Graziani, M.; Haberkamp, M.; Habert, M. O.; Hampel, H.; Herholz, K.; Karran, E.; Kim, S. H.; Koronyo, Y.; Koronyo-Hamaoui, M.; Lamari, F.; Langevin, T.; Lehericy, S.; Lista, S.; Lorenceau, J.; Mapstone, M.; Neri, C.; Nistico, R.; Nyasse-Messene, F.; O'Bryant, S. E.; Perry, G.; Ritchie, C.; Rojkova, K.; Rossi, S.; Santarnecchi, E.; Schneider, L. S.; Sporns, O.; Toschi, N.; Verdooner, S. R.; Vergallo, A.; Villain, N.; Welikovitch, L.; Woodcock, J.; Younesi, E