Prise en compte de la surdisposition par des modèles à mélange de Poisson

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Early Detection of Poor Outcome after Mild Traumatic Brain Injury: Predictive Factors Using a Multidimensional Approach a Pilot Study

Mild traumatic brain injury (MTBI) is a common condition within the general population, usually with good clinical outcome. However, in 10–25% of cases, a post-concussive syndrome (PCS) occurs. Identifying early prognostic factors for the development of PCS can ensure widespread clinical and economic benefits. The aim of this study was to demonstrate the potential value of a comprehensive neuropsychological evaluation to identify early prognostic factors following MTBI. We performed a multi-center open, prospective, longitudinal study that included 72 MTBI patients and 42 healthy volunteers matched for age, gender, and socioeconomic status. MTBI patients were evaluated 8–21 days after injury, and 6 months thereafter, with a full neurological and psychological examination and brain MRI. At 6 months follow-up, MTBI patients were categorized into two subgroups according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as having either favorable or unfavorable evolution (UE), corresponding to the presence of major or mild neurocognitive disorder due to traumatic brain injury. Univariate and multivariate logistical regression analysis demonstrated the importance of patient complaints, quality of life, and cognition in the outcome of MTBI patients, but only 6/23 UE patients were detected early via the multivariate logistic regression model. Using several variables from each of these three categories of variables, we built a model that assigns a score to each patient presuming the possibility of UE. Statistical analyses showed this last model to be reliable and sensitive, allowing early identification of patients at risk of developing PCS with 95.7% sensitivity and 77.6% specificity

Transfer and propagation reactions in free-radical copolymerization

The contribution of entropic factors to the penultimate unit effect in free-radical copolymerizations is discussed and exemplified. In addition, significant penultimate unit effects on radical selectivity in transfer reactions are demonstrated and are shown to have a significant polar component. Further, ring-opening copolymerization studies are presented and describe surprising results that seem to originate from strong solvent effects in copolymerization. These results could not have been predicted with current knowledge, prior to the experiment. The present contribution demonstrates in detail that radical reactions are highly complex and there are significant dangers and drawbacks in employing simplified kinetic models when in search of fundamental understanding

Mitochondrial OPA1 deficiency is associated to reversible defects in spatial memory related to adult neurogenesis in mice

Mitochondria are integrative hubs central to cellular adaptive pathways. Such pathways are critical in highly differentiated post-mitotic neurons, the plasticity of which sustains brain function. Consequently, defects in mitochondria and in their dynamics appear instrumental in neurodegenerative diseases and may also participate in cognitive impairments. To directly test this hypothesis, we analyzed cognitive performances in a mouse mitochondria-based disease model, due to haploinsufficiency in the mitochondrial optic-atrophy-type-1 (OPA1) protein involved in mitochondrial dynamics. In males, we evaluated adult hippocampal neurogenesis parameters using immunohistochemistry. We performed a battery of tests to assess basal behavioral characteristics and cognitive performances, and tested putative treatments. While in Dominant Optic Atrophy (DOA) mouse models, the known main symptoms are late onset visual deficits, we discovered early impairments in hippocampus-dependent spatial memory attributable to defects in adult neurogenesis. Moreover, less connected adult-born hippocampal neurons showed a decrease in mitochondrial content. Remarkably, voluntary exercise or pharmacological treatment targeting mitochondrial dynamics restored spatial memory in DOA mice. Altogether, our study identifies a crucial role for OPA1-dependent mitochondrial functions in adult neurogenesis, and thus in hippocampal-dependent cognitive functions. More generally, our findings show that adult neurogenesis is highly sensitive to mild mitochondrial defects, generating impairments in spatial memory that can be detected at an early stage and counterbalanced by physical exercise and pharmacological targeting of mitochondrial dynamics. Thus, amplification of mitochondrial function at an early stage appears beneficial for late-onset neurodegenerative diseases. Significance Statement The adult hippocampus continues to produce new neurons in mammals. These new neurons are highly sensitive to mitochondrial perturbation. Dominant optic atrophy (DOA) is a rare disease mainly caused by mutations in the gene coding the mitochondrial protein OPA1. Using a mouse model of OPA1 deficiency, we found that hippocampal new neurons have dendritic spine density defects and altered mitochondrial content. We further detected impairments in spatial memory capacities relying on adult-neurogenesis. We report that these memory impairments can be corrected by physical exercise and pharmacological treatment targeting mitochondria in mice. Our results indicate that early detection of spatial memory deficits related to adult neurogenesis may allow a precocious action in pathologies involving mitochondria, such as DOA or neurodegenerative diseases

Epidemiology, Mortality and Healthcare Resource Utilization Associated With Systemic Sclerosis-Associated Interstitial Lung Disease in France

International audienceObjectives: To investigate the clinical characteristics, epidemiology, survival estimates and healthcare resource utilization and associated costs in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in France.</p> and nbsp;</p> Methods: The French national administrative healthcare database, the Systeme National des Donnees de Sante (SNDS), includes data on 98.8% of the French population, including data relating to ambulatory care, hospitalizations and death. In our study, claims data from the SNDS were used to identify adult patients with SSc-ILD between 2010 and 2017. We collected data on clinical features, incidence, prevalence, survival estimates, healthcare resource use and costs.</p> and nbsp;</p> Results: In total, 3,333 patients with SSc-ILD were identified, 76% of whom were female. Patients had a mean age [standard deviation (SD)] of 60.6 (14.4) years and a mean (SD) individual study duration of 3.9 (2.7) years. In 2016, the estimated overall incidence and prevalence were 0.69/100,000 individuals and 5.70/100,000 individuals, respectively. The overall survival estimates of patients using Kaplan-Meier estimation were 93, 82, and 55% at 1, 3, and 8 years, respectively. During the study, 98.7% of patients had and GE;1 hospitalization and 22.3% of patients were hospitalized in an intensive care unit. The total annual mean healthcare cost per patient with SSc-ILD was euro 25,753, of which euro 21,539 was related to hospitalizations.</p> and nbsp;</p> Conclusions: This large, real-world longitudinal study provides important insights into the epidemiology of SSc-ILD in France and shows that the disease is associated with high mortality, healthcare resource utilization and costs. SSc-ILD represents a high burden on both patients and healthcare services.</p> and nbsp;</p&gt

Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)

International audienceBACKGROUND: There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database.METHODS: The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD.RESULTS: We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan-Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622-54,287) and the median annual cost per patient was €18,362 (6856-52,026), of which €11,784 (3003-42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests.CONCLUSIONS: This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842

Mitochondrial OPA1 deficiency causes reversible defects in adult neurogenesis-associated spatial memory in mice

Abstract Mitochondria are integrative hubs central to cellular adaptive pathways. Such pathways are critical in highly differentiated post-mitotic neurons, the plasticity of which sustains brain function. Consequently, defects in mitochondrial dynamics and quality control appear instrumental in neurodegenerative diseases and may also participate in cognitive impairments. To directly test this hypothesis, we analyzed cognitive performances in a mouse mitochondria-based disease model, due to haploinsufficiency in the mitochondrial optic-atrophy-type-1 (OPA1) protein. While in Dominant Optic Atrophy (DOA) models, the known main symptoms are late onset visual deficits, we discovered early impairments in hippocampus-dependent spatial memory attributable to defects in adult neurogenesis. Moreover, less connected hippocampal adult-born neurons showed a decrease in mitochondrial content. Remarkably, modulating mitochondrial function through voluntary exercise or pharmacological treatment restored spatial memory. Altogether, our study identifies a crucial role for OPA1-dependent mitochondrial functions in adult neurogenesis, and thus in hippocampal-dependent cognitive functions. More generally, our findings show that adult neurogenesis is highly sensitive to mild mitochondrial defects, generating impairments in spatial memory that can be detected at an early stage and counterbalanced by physical exercise and pharmacological targeting of mitochondrial dynamics. Thus, early amplification of mitochondrial function appears beneficial for late-onset neurodegenerative diseases

Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions.

BACKGROUND AND AIM: The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. METHODS: Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. RESULTS: The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33-0.49) to 0.64 (CI 95% 0.61-0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). CONCLUSION: The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133

Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study)

International audienceIn patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking. We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010–2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses. In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01). In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality