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Defibrillation Testing During Implantation of Subcutaneous Implantable Cardioverter Defibrillators
No full textInternational audienceBackground: Defibrillation testing (DT) remains recommended during subcutaneous implantable cardioverter defibrillator (S-ICD) implantation due to limited supporting evidence.Objectives: The objective of this study was to evaluate the long-term impact of DT during S-ICD implantation.Methods: The HONEST (coHOrte fraNcaise des dEfibrillateurs Sous cuTanés) study is a nationwide, ongoing observational study, including all S-ICD recipients in France (2012-2019). Five-year endpoints were centrally adjudicated, and propensity score-weighted analyses compared outcomes by DT status.Results: Among 4,924 patients, DT was performed in 4,066 (82.6%), decreasing from 85.4% (2012-2014) to 66.9% in 2019 (P < 0.001). Nontested patients were older (51.2 vs 49.6 years; P = 0.007), had lower left ventricular ejection fraction (37.6% vs 43.3%; P < 0.001), and were more frequently implanted for primary prevention (68.0% vs 62.4%; P = 0.002) and structural heart disease (84.9% vs 76.8%; P < 0.001). DT-related complications occurred in 0.1%, including 2 deaths. Failure rate was 1.0%, with 87.8% undergoing corrective reinterventions. Independent predictors of DT failure were elevated shock impedance (≥89 Ω; OR: 4.60; 95% CI: 2.32-9.66; P < 0.001) and obesity (body mass index ≥30 kg/m2; OR: 2.17; 95% CI: 1.01-4.55; P = 0.007). After adjustment, DT omission was not associated with increased risks of overall mortality (HR: 1.17; 95% CI: 0.86-1.61; P = 0.313), cardiovascular mortality (HR: 1.04; 95% CI: 0.70-1.56; P = 0.846), sudden cardiac death (HR: 0.27; 95% CI: 0.04-1.72; P = 0.167), and appropriate (HR: 1.01; 95% CI: 0.78-1.30; P = 0.945) or inappropriate shocks (HR: 0.98; 95% CI: 0.78-1.23; P = 0.865). Combined rates of ineffective shocks or undetected ventricular arrhythmias were similar (0.05 vs 0.06 per 100 person-years).Conclusions: Our findings suggest that DT can be safely omitted in the majority of S-ICD recipients, whereas selective DT may be considered in higher-risk subgroups. (S-ICD French Cohort Study (HONEST); NCT05302115)
Assessing Cancer-Related Cognitive Impairment for breast cancer survivors with speech analysis
No full textInternational audienceBackground: This paper presents a first study on the assessment of Cancer-Related Cognitive Impairment (CRCI) with speech analysis. CRCI is a reported change in cognitive performance by cancer patients, which is too subtle to be detected by the current tests in use. Speech analysis might provide a solution to this issue. Speech analysis can be instrumental in the detection of subtle cognitive impairment, as speech contains fine-grained segmental and suprasegmental parameters that are sensitive to changes in cognition. Pauses have particularly been highlighted as potential behavioral markers of neurocognitive disorders. However, the absence of simple, detailed methods compromises the feasibility of speech analyses in clinical practice.Objectives: This study aims (i) to identify breast cancer survivors with CRCI using a new practical method centered on speech pauses, and (ii) to provide the detailed protocol that supports this study, which is intended to be applicable in clinical contexts. Methods: Thirty-three breast cancer survivors with a cognitive complaint, eleven breast cancer survivors without a cognitive complaint and thirteen controls were included in the study. Participants were instructed to tell a picture-based story. Their narratives were recorded, automatically transcribed with Whisper, and analyzed using the SPPAS and Praat software. Silent pauses, filled pauses, and sustained vowels were annotated, then processed in RStudio for statistical analysis.Results: Only silent pause duration was significantly longer for breast cancer survivors with a cognitive complaint than for controls. Conclusions: The results suggest that silent pause duration is a good marker for detecting CRCI. Automatizing the transcription and annotation of speech data improves the feasibility of speech analysis in clinical contexts, although a manual check is required
Dietary Protein Intake Recommendations for Patients with Non-Dialysis-Dependent CKD: What Should Healthcare Providers Do?
No full textInternational audienceProtein intake is crucial to maintain human health, and an adequate quantity and quality of dietary protein intake (DPI) is particularly important in patients with CKD. Both an insufficient amount of DPI ( i.e ., \textless0.6 g/kg body weight (body wt)/d) and an excess amount of DPI ( i.e ., \textgreater1.3 g/kg body wt/d) pose potential health hazards in patients with CKD stages 3-5. Therefore, to optimize patient outcomes, healthcare providers should be familiar with the effects of both inadequate and excessive DPI in this population. The Kidney Disease Outcome Quality Initiative guidelines on DPI are rooted in detailed analyses of available scientific evidence and provide detailed recommendations regarding different dietary interventions strategies to achieve optimal quantity and quality of DPI. The more recent Kidney Disease Improving Global Outcomes guidelines on CKD management have a substantially broader scope and include a relatively brief section on diet, recommending a DPI of 0.8 g/kg body wt/d, emphasizing the need to avoid a DPI of \textgreater1.3 g/kg body wt/d. Besides aiming for a DPI of approximately 0.6-0.8 g/kg body wt/d in patients with CKD stages 3-5, successful practical implementation of dietary interventions requires an individualized approach which considers patient characteristics, such as sociocultural norms, habitual dietary habits, and nutrition literacy as well as systemic factors such as feasibility and availability of interventions
Amikacin use in critically ill patients requiring renal replacement therapy: the AMIDIAL-ICU study
No full textInternational audienceBACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is common in intensive care units (ICUs), yet optimal amikacin dosing in this context remains poorly understood. METHODS: We conducted a prospective observational study across 18 French hospitals from April 2020 to January 2022. Adult ICU patients (aged \textgreater 18 years) receiving their first amikacin dose while on RRT were included. Data on demographics, RRT modalities, amikacin dosing, and therapeutic drug monitoring were collected. Using a pharmacokinetic modeling approach, we evaluated various amikacin regimens and simulated target attainment probabilities across different minimum inhibitory concentrations (MICs). RESULTS: A total of 111 patients were included, with approximately two-thirds receiving continuous RRT. The median amikacin dose was 27 (25-30) mg/kg. Amikacin peak (Cmax) and trough concentrations were monitored in 53 (47.8%) and 76 (68.5%) patients, respectively. Continuous RRT and a history of chronic kidney disease reduced dialytic clearance. For a MIC ≤ 4 mg/L, a 15 mg/kg amikacin dose achieved Cmax/MIC and AUC/MIC targets in ≥ 90% of patients on intermittent dialysis, while 20 mg/kg was required for those on continuous dialysis. For a MIC = 8 mg/L, a 30 mg/kg dose was necessary to achieve Cmax/MIC ≥ 8. CONCLUSIONS: Our findings highlight suboptimal adherence to amikacin monitoring guidelines in ICU patients on RRT. Using pharmacokinetic modeling, we identified amikacin dosing recommendations ranging from 15 to 35 mg/kg to optimize efficacy and minimize risks, depending on MIC and dialysis modality
Three-State Gene Expression Model Parameterized for Single-Cell Multi-Omics Data
No full textInternational audienceAbstract We present a novel three-state gene expression model designed to elucidate the underlying mechanisms of mRNA transcription and its regulation. Our model incorporates gene regulatory processes by explicitly including a transcription factor-bound state, thereby capturing the dynamic interplay between transcription activation and chromatin dynamics. We fit the model to paired single-cell ATAC-seq and single-cell RNA-seq data, as these data give us simultaneous information on a gene’s transcriptional state and its accompanying chromatin state. Working at the pseudo-bulk level, we extract biologically meaningful high-level descriptors from homogeneous cell (sub)populations, such as the mean and variance of gene expression as well as the fraction of accessible chromatin. Crucial to the computational feasibility of our approach, these descriptors can be analytically related to our model parameters. Despite the increased complexity needed to capture regulatory processes in our model, it remains sufficiently parsimonious to infer parameters reliably from experimental data. Each parameter has a clear biological interpretation, reflecting properties such as burst frequency, chromatin opening and closing dynamics, and basal or regulated expression. Fitting the model to a large collection of genes allows us to analyze the parameters and distinguish so-called gene expression strategies. The model parameters reveal a small number of distinct expression strategies among gene clusters, providing data-driven novel insight into context-dependent regulation of gene expression
Improvement of apathy in early Parkinson’s disease
No full textInternational audienceABSTRACT Background Speech impairment is a recognized but unpredictable adverse effect of sub‐thalamic nucleus deep brain stimulation (STN‐DBS) for Parkinson's disease (PD). Objectives To evaluate the prevalence of speech impairment 1 year after STN‐DBS in PD patients and to determine the predictive factors for speech outcome following STN‐DBS. Methods Data for 417 patients from the French national PREDISTIM study were collected preoperatively. The combined effect of medical treatment and surgery on speech was compared using specific items from dedicated clinical scales (MDS‐UPDRS III.1: primary endpoint) and patient self‐assessment questionnaires (items 34 and 35 of the PDQ39: secondary endpoints). For each variable, three patient groups were generated according to speech outcome at 1 year: worsening, stability, and improvement. In the second step analysis, the three groups were compared for demographic and clinical variables at baseline and STN‐DBS parameters. Results There was a significant deterioration in speech of all considered items 1 year after combined STN‐DBS and dopaminergic treatment. Four predictive factors for speech deterioration were detected: (i) the absence of preoperative speech impairment ( p < 0.001); (ii) severity of motor activity of daily living (MDS‐UPDRS II off total score) ( p = 0.037); (iii) high‐intensity stimulation of the left electrode (i.e., above 3.6 V) ( p = 0.046); and (iv) the absence of any change in non‐motor experiences of daily life (MDS‐UPDRS I total score) ( p = 0.048). Conclusions Speech outcome should be carefully monitored after STN‐DBS, especially in PD patients without preoperative speech impairment, with motor difficulties in daily‐living activities, and with increased left electrode intensity. Trial Registration ClinicalTrials.gov identifier: NCT02360683
Évaluation des méthodes de découverte d'EDP pour la modélisation multi-échelle des signaux biologiques.
No full textInternational audienceBiological systems are non-linear, include unobserved variables and the physical principles that govern their dynamics are partly unknown. This makes the characterization of their behavior very challenging. Notably, their activity occurs on multiple interdependent spatial and temporal scales that require linking mechanisms across scales. To address the challenge of bridging gaps between scales, we leverage partial differential equations (PDE) discovery. PDE discovery suggests meso-scale dynamics characteristics from micro-scale data. In this article, we present our framework combining particle-based simulations and PDE discovery and conduct preliminary experiments to assess equation discovery in controlled settings. We evaluate five state-of-the-art PDE discovery methods on particle-based simulations of calcium diffusion in astrocytes. The performances of the methods are evaluated on both the form of the discovered equation and the forecasted temporal variations of calcium concentration. Our results show that several methods accurately recover the diffusion term, highlighting the potential of PDE discovery for capturing macroscopic dynamics in biological systems from microscopic data.Les systèmes biologiques sont non-linéaires, comprennent des variables non observées et les principes physiques qui régissent leurs dynamiques sont en partie inconnus. Cela rend la caractérisation de leur comportement très difficile. En particulier, leur activité se produit à de multiples échelles spatiales et temporelles interdépendantes, ce qui nécessite des mécanismes de liaison entre les échelles. Pour relever le défi de combler les lacunes entre les échelles, nous nous appuyons sur la découverte d'équations différentielles partielles (EDP). La découverte d'EDP suggère des caractéristiques dynamiques à méso-échelle à partir de données à micro-échelle. Dans cet article, nous présentons notre cadre combinant les simulations à base de particules et la découverte d'EDP et nous menons des expériences préliminaires pour évaluer la découverte d'équations dans des environnements contrôlés. Nous évaluons cinq méthodes de découverte d'EDP de pointe sur des simulations à base de particules de la diffusion du calcium dans les astrocytes. Les performances des méthodes sont évaluées à la fois sur la forme de l'équation découverte et sur les variations temporelles prévues de la concentration de calcium. Nos résultats montrent que plusieurs méthodes récupèrent avec précision le terme de diffusion, soulignant le potentiel de la découverte d'EDP pour capturer les dynamiques macroscopiques dans les systèmes biologiques à partir de données microscopiques
Prevention of aspiration pneumonia recurrences
No full textInternational audienceContext: Aspiration pneumonia occurs after a documented aspiration or in patients with aspiration risk factors, suggesting a potential oropharyngeal portal of entry for the responsible pathogens. Strategies aimed at preventing recurrences are based on the identification of risk factors, their modification, and the implementation of appropriate corrective measures.Methods: A comprehensive review of the literature (2000-2025) on the prevention of aspiration pneumonia was conducted.Results: Treatments likely to exacerbate swallowing disorders must be reassessed, particularly anticholinergics, sedatives, and psychotropic drugs. No treatment was significantly effective in directly preventing aspiration pneumonia. Nutritional requirements are met using enteral nutrition, but it increases oral bacterial colonization, oral biofilm thickness, and muscle weakness. A series of measures (semi-sitting positioning in patients with impaired awareness or enteral nutrition, speech therapy, rehabilitation, and elimination of dental biofilm) were significantly effective in preventing aspiration pneumonia. Adapting food texture and thickening liquids are measures being considered to reduce the risks, despite the potential impact on the quality of life and on nutritional intake.Conclusion: A multidisciplinary assessment is recommended after an episode of pneumonia in the elderly to identify the pathogen's route of entry and to establish a plan to prevent recurrences. Future research will need to determine priorities among the various measures proposed to optimize management strategies
Comprehensive analysis of sickle β+-thalassemia genotypes and their associated HbA levels in France
No full textInternational audienceWe retrospectively reviewed the clinical records of 228 HbS/β+-thal patients. The different genotypes were distributed into three groups according to their mean residual HbA levels: <10 % (group 1; n = 22), between 10 and 20 % (group 2; n = 175) and > 20 % (group 3; n = 31). Routine red blood cells and hemoglobin parameters were compared between the three groups. Sixteen different sickle β+-thal genotypes were identified but only four of them were associated with a residual HbA level below 10 %. Patients of this group exhibited a more severe anemia (Hb < 10 g/dL; reticulocytes >200 G/L) compared to the two other groups. However, no difference could be observed on those parameters between patients of group 2 and 3, as well as for the main RBC parameters. According to our study, >80 % of the sickle β+-thalassemia patients in France have a residual HbA level beyond 10 % and a mild to moderate anemia. Only four β+-thal variations (all affecting the splicing process) would lead to a potentially severe SCD syndrome in association with HbS (HbA < 10 %) but this result should be confirmed in a prospective clinical study
