47 research outputs found

    Características del trabajo y salud ocupacional: validación y propuesta de una versión abreviada del Work Design Questionnaire

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    Interest in the study of work characteristics to explain how an individual's relationship with the work environment can lead to maladaptive responses has taken on renewed importance in the light of increasing concern for the development of healthy organizations and organizational diversity. This study aims to develop a shortened version of the Work Design Questionnaire (WDQ) with a view to facilitating its use and interpretation. The psychometric properties of this shorter questionnaire were tested in a multi-sectoral sample of workers in Spain, with due consideration given to the gender measurement invariance. For this purpose, we applied the questionnaire to a sample of 500 workers and analyzed the relationship between the answers provided to WDQ and specific occupational health variables (satisfaction, well-being and emotional exhaustion). Results showed adequate reliability and criterion-oriented validity for the shortened version of the WDQ, that is, the WDQ18-S, as well as evidence of factorial invariance across gender. We then discuss the results and their implications for the application of the WDQ in further research and the field of occupational health and psychosocial risks prevention.El interés por el estudio de las características del trabajo para explicar cómo la relación de un individuo con el entorno laboral puede conducir a respuestas desadaptativas ha cobrado una importancia renovada a la luz de la creciente preocupación por el desarrollo de organizaciones saludables y por la diversidad organizacional. Este estudio tiene como objetivo desarrollar una versión abreviada del Work Design Questionnaire (WDQ) con el fin de facilitar su uso e interpretación en este contexto. Las propiedades psicométricas de este cuestionario reducido se probaron en una muestra multisectorial de trabajadores en España. Para ello, aplicamos el cuestionario a una muestra de 500 trabajadores y analizamos la relación entre las carácterísiticas del trabajo y las variables seleccionadas de salud ocupacional (satisfacción, bienestar y agotamiento emocional). Los resultados mostraron una fiabilidad y una validez orientada al criterio adecuadas para la versión abreviada del WDQ, esto es, el WDQ18-S, así como evidencia de invarianza factorial de género. Posteriormente se discuten los resultados y sus implicaciones para el uso del WDQ en el ámbito aplicado e investigador de la salud ocupacional y la prevención de riesgos laborales

    Supporting central nervous system neuroprotection and remyelination by specific TLR4 antagonism

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    ApTOLL is an aptamer specifically designed to antagonize toll-like receptor 4 (TLR4), which is involved in the innate immunity that promotes inflammatory responses in several diseases, including multiple sclerosis (MS). MS is a chronic, immune, demyelinating and neurodegenerative disease of the central nervous system that represents the second most important cause of neurological disability in young adults. The drugs currently available to treat this disease are immunomodulators and, to date, there are no therapeutic remyelinating drugs available to manage MS. In this study, we show that TLR4 is located in post-mortem cortical lesions of MS patients and as a result, we evaluated the effect of its inhibition by ApTOLL in two different animal models of MS, that of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model. ApTOLL administration ameliorated the clinical symptomatology of the affected mice, which was associated with better preservation and restoration of myelin and oligodendrocytes in the demyelinated lesions of these animals. This revealed not only an immunomodulatory but also a remyelinating effect of the treatment with ApTOLL which was corroborated on purified cultures of rodent and adult human oligodendrocyte precursor cells (OPCs). In summary, the molecular nature of ApTOLL and its mechanism of action strongly supports its further study and use in novel strategies to treat MS and eventually, other demyelinating diseases.This work was supported by grant IND2018/BMD-9751 (Programa de Doctorados Industriales, Comunidad de Madrid, Spain), SAF2016-77575-R (Spanish Ministerio de Economía, Industria y Competitividad-MINECO), and the contract for technological support ApTLR2019-PC-MS-001 (AptaTargets, S.L., Spain) to FdC. BF-G is currently hired by Aptatargets S.L., PG-M is hired under PEJ-2020-AI/BMD-18541 de la Comunidad de Madrid, Spain (associated with the youth guarantee fund to FdC), SN had a predoctoral contract from the UCLM and was hired under SAF2012-40023, SAF2016- 77575-R, RD12-0032/0012 and RD16-0015/0019 (Spanish Ministerio de Economía, Industria y Competitividad-MINECO) and IND2018/BMD-9751, YL has been contracted under ReTics and SAF (to FdC). We thank David Segarra and Mª Eugenia Zarabozo (AptaTargets S.L.) for their constant technological support, Laude Garmendia for her indispensable constant help at the animal facility (Instituto Cajal-CSIC), including the extra effort during Covid-19 pandemics, Profs María Ángeles Moro (Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid and Universidad Complutense de Madrid, Spain) and Ignacio Lizasoaín (Universidad Complutense de Madrid, Spain) for lending us the TLR4 knockout mice, and the former GNDe member Dr. Carolina MeleroJerez (currently working at JazzPharma, Spain) for the initial training of BF-G on EAE animal model and different techniques at the laboratory. Human samples were supplied by the UK Multiple Sclerosis Tissue Bank, funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland (registered charity 207495).N

    Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring:a CENTER-TBI study

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    Objective: To compare outcomes between patients with primary external ventricular device (EVD)–driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)–driven treatment. Methods: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with “center” as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. Results: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36–1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34–2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. Conclusion: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor–guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. Protocol: The core study is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).</p

    Quality indicators for patients with traumatic brain injury in European intensive care units

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    Background: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measur

    Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe

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    Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatme

    Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

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    Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

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    INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

    Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study

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    Background: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. Methods: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subj

    Tracheal intubation in traumatic brain injury

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    Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79–1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65–1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration: NCT02210221
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