Among the paintings and engravings found in the Chauvet-Pont d'Arc cave (Ardèche, France), several peculiar spray-shape signs have been previously described in the Megaloceros Gallery. Here we ...document the occurrence of strombolian volcanic activity located 35 km northwest of the cave, and visible from the hills above the cave entrance. The volcanic eruptions were dated, using 40Ar/39Ar, between 29 ± 10 ka and 35 ± 8 ka (2σ), which overlaps with the 14C AMS and thermoluminescence ages of the first Aurignacian occupations of the cave in the Megaloceros Gallery. Our work provides the first evidence of an intense volcanic activity between 40 and 30 ka in the Bas-Vivarais region, and it is very likely that Humans living in the Ardèche river area witnessed one or several eruptions. We propose that the spray-shape signs found in the Chauvet-Pont d'Arc cave could be the oldest known depiction of a volcanic eruption, predating by more than 34 ka the description by Pliny the Younger of the Vesuvius eruption (AD 79) and by 28 ka the Çatalhöyük mural discovered in central Turkey.
The Seine, Yonne and Somme are the main rivers draining northwestern France and flowing into the Channel. During Pleistocene cold stages they were tributaries of the “Fleuve Manche”. They are ...characterised by well-developed stepped terrace systems showing up to 10 incision steps for the last 1Ma. After 15 years of research and the synthesis of stratigraphical, sedimentological, bioclimatical data and numerical dating, these terrace systems are interpreted as the response of the fluvial environments to climatic cyclicity, superimposed on a background of slow tectonic uplift. The comparison of these three terrace systems shows that the incision budget is similar within the studied area (about 55–65m/1Ma), implying relative homogeneity of uplift. In the main part of the area, beyond marine influence, the analysis of each stepped alluvial formation shows regular sediment balance generally composed of coarse periglacial gravels (pleniglacial), covered by fine-grained sediments locally overlain by calcareous tufa (interglacial). However, in the Lower Seine valley, close to the present coast, the low terrace includes two estuarine interglacial units interbedded within periglacial gravel units. Nevertheless, until recently evidence of full interglacial conditions remained elusive in fluvial contexts, especially in the Somme. To address these issues a new research programme has been launched on tufa deposits that are the best candidate to register the climatic optimum. Initial results from la Celle (Seine), Saint-Acheul and Caours (Somme) allow palaeoenvironmental reconstructions of MIS 11 and 5e, and thus confirm the importance of calcareous tufa to define a reference record of Pleistocene Interglacials for northern France. Moreover, it has been previously demonstrated that the main incision leading to terrace formation can be attributed to the transition between interglacial and glacial (during early glacial phases). The new results from interglacial records have important implications concerning the precise occurrence of the major incision phases within the climatic cycle as they provide the starting point immediately preceding downcutting.
Sarcoidosis-associated pulmonary hypertension (SAPH) is a very severe complication of the disease, largely impacting its morbidity and being one of its strongest predictors of mortality. With the ...recent modifications of the hemodynamic definition of pulmonary hypertension (mean arterial pulmonary pressure >20 instead of <25 mmHg,) its prevalence is presently not precisely known, but it affects from 3 to 20% of sarcoid patients; mostly, although not exclusively, those with an advanced, fibrotic pulmonary disease. Its gold-standard diagnostic tool remains right heart catheterization (RHC). The decision to perform it relies on an expert decision after a non-invasive work-up, in which echocardiography remains the screening tool of choice. The mechanisms underlying SAPH, very often entangled, are crucial to define, as appropriate and personalized therapeutic strategies will aim at targeting the most significant ones. There are no recommendations so far as to the indications and modalities of the medical treatment of SAPH, which is based upon the opinion of a multidisciplinary team of sarcoidosis, pulmonary hypertension and sometimes lung transplant experts.
Medication adherence plays a critical role in controlling the evolution of chronic disease, as low medication adherence may lead to worse health outcomes, higher mortality, and morbidity. Assessment ...of their patients' medication adherence by clinicians is essential for avoiding inappropriate therapeutic intensification, associated health care expenditures, and the inappropriate inclusion of patients in time- and resource-consuming educational interventions. In both research and clinical practices the most extensively used measures of medication adherence are patient-reported outcome measures (PROMs), because of their ability to capture subjective dimensions of nonadherence. Machine learning (ML), a subfield of artificial intelligence, uses computer algorithms that automatically improve through experience. In this context, ML tools could efficiently model the complexity of and interactions between multiple patient behaviors that lead to medication adherence. This study aimed to create and validate a PROM on medication adherence interpreted using an ML approach. This cross-sectional, single-center, observational study was carried out a French teaching hospital between 2021 and 2022. Eligible patients must have had at least 1 long-term treatment, medication adherence evaluation other than a questionnaire, the ability to read or understand French, an age older than 18 years, and provided their nonopposition. Included adults responded to an initial version of the PROM composed of 11 items, each item being presented using a 4-point Likert scale. The initial set of items was obtained using a Delphi consensus process. Patients were classified as poorly, moderately, or highly adherent based on the results of a medication adherence assessment standard used in the daily practice of each outpatient unit. An ML-derived decision tree was built by combining the medication adherence status and PROM responses. Sensitivity, specificity, positive and negative predictive values (NPVs), and global accuracy of the final 5-item PROM were evaluated. We created an initial 11-item PROM with a 4-point Likert scale using the Delphi process. After item reduction, a decision tree derived from 218 patients including data obtained from the final 5-item PROM allowed patient classification into poorly, moderately, or highly adherent based on item responses. The psychometric properties were 78% (95% CI 40%-96%) sensitivity, 71% (95% CI 53%-85%) specificity, 41% (95% CI 19%-67%) positive predictive values, 93% (95% CI 74%-99%) NPV, and 70% (95% CI 55%-83%) accuracy. We developed a medication adherence tool based on ML with an excellent NPV. This could allow prioritization processes to avoid referring highly adherent patients to time- and resource-consuming interventions. The decision tree can be easily implemented in computerized prescriber order-entry systems and digital tools in smartphones. External validation of this tool in a study including a larger number of patients with diseases associated with low medication adherence is required to confirm its use in analyzing and assessing the complexity of medication adherence.
Abstract
Background
Interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with systemic sclerosis and combined ...PH and ILD (SSc-PH-ILD) generally have a poor prognosis. Predictors of survival and of potential benefit of treatment are lacking in patients with SSc-PH-ILD.
Objective
To identify specific plasma protein expression patterns associated with survival in patients with SSc-PH-ILD.
Materials and methods
Post-hoc analysis of a prospective multicenter French study in patients with PH-ILD. An untargeted proteomic analysis using mass spectrometry was performed to identify plasma protein changes associated with long-term overall survival in patients with SSc-PH-ILD.
Results
Thirty two patients were included in the analysis, of whom 13 died during follow-up (median survival: 76.5 months). At baseline, survivors had less severe hemodynamic impairment pulmonary vascular resistance of 4.4 Wood Units (IQR 3–5.2) vs. 6.2 Wood Units (IQR 4.2–10.7) and higher carbon monoxide diffusing capacity median 39% (IQR 35–44%) vs. 25% (IQR 22–30.5%), than the 13 patients who died. Seven proteins, associated with haemostasis and fibrosis, were differentially expressed according to patients’ survival. In the survivor group, two proteins were increased (ADAMTS13, SERPIND1) and five were decreased (PTGDS, OLFM1, C7, IGFBP7, FBN1) compared to the non-survivor groups.
Conclusion
The prognosis of SSc-PH-ILD patients is poor. This proteomic approach found 7 plasma proteins (involved in haemostasis and fibrosis pathways) associated with survival. These potential biomarkers may be good candidates to prognostic enrichment.
There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and ...functional characteristics as well as outcomes of patients with severe physiologic impairment.
IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated.
There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DL
28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen (Formula: see text group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWT
group had a better transplant-free survival than the Formula: see text group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001).
IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.
Abstract Introduction Up to 50% of patients with pulmonary embolism (PE) present lung perfusion defects after six months of anticoagulant treatment, suggesting residual pulmonary vascular obstruction ...(RPVO). The risk of recurrence in patients with RPVO remains unknown. The present study aims to assess the risk of recurrent venous thromboembolism (VTE) in patients with RPVO after a first symptomatic episode of PE. Methods Consecutive patients who survived a first objectively proven acute PE, treated for at least three months with anticoagulants, were included and followed prospectively. RPVO was defined as a pulmonary vascular obstruction of > 10% on ventilation/perfusion lung scan performed at inclusion. Objectively proven VTE recurrences were registered and confirmed by an investigator unaware of the result of the ventilation/perfusion lung scan. Results Among the 310 patients (median age: 61 years) included in the study, 60 (19%) had RPVO. During a median follow-up of 51.3 months, 66 patients (21.2%, 95% CI 17.5–26.7) experienced recurrent VTE. In an adjusted cox proportional hazards analysis, we identified RPVO (HR 1.94; 95% CI 1.11–3.39; p = 0.026) and unprovoked PE (HR 3.56; 95% CI 1.79–7.07; p = 0.00051) as independent risk factors for recurrent VTE whereas extended anticoagulation therapy (HR 0.19; 95% CI 0.07–0.55; p = 0.00014) was associated with a low risk of recurrence. Conclusion The results suggest that RPVO is an independent risk factor of recurrent VTE after a first PE.
Although sarcoidosis is generally regarded as a benign condition, approximately 20-30% of patients will develop a chronic and progressive disease. Advanced pulmonary fibrotic sarcoidosis and cardiac ...involvement are the main contributors to sarcoidosis morbidity and mortality, with failure of the liver and/or kidneys representing additional life-threatening situations. In this review, we discuss diagnosis and treatment of each of these complications and highlight how the integration of clinical, pathological and radiological features may help predict the development of such high-risk situations in sarcoid patients.
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