Tuberculosis treatment outcomes among precarious patients in France.

OBJECTIVES: Patients lost to follow-up and treatment failure in tuberculosis disease (TB) are major public health issues. In the absence of appropriate treatment, approximately 70 % of smear-positive patients will die within 10 years of disease progression. This study, conducted in the French region with the highest incidence, aimed to assess tuberculosis treatment outcomes and its determinants. PATIENTS AND METHODS: A prospective, multicenter cohort study (CO1TB) of adults and children treated for TB was conducted in four hospitals in the North of Paris. Treatment outcome at 1 year and associated socioeconomic and clinical factors were studied by multivariate logistic regression. RESULTS: Among 145 TB cases included from May 2018 to January 2020, patients were mainly born abroad and most lived in difficult socioeconomic conditions. During treatment, 25/145 (17 %) patients experienced adverse effects, which were not significantly associated with discontinuation of treatment (p = 0.99). At 1 year, 114 (78 %) had completed treatments, 26 (19 %) were lost to follow-up, three (2.1 %) were still being treated and two (1.4 %) had died. In the multivariate analysis, a history of TB was significantly associated with unfavorable treatment outcome (aOR = 5.3, 95 %CI (1.5;18.6) and a trend towards significance (p < 0.2) was observed among patients aged under 24 years (aOR = 2.9, 95 %-CI 0.95;8.5). CONCLUSION: In this precarious population, socioeconomic conditions were not found to be associated with unfavorable treatment outcome, whereas history of tuberculosis and young age played a role. Increased monitoring is thus required for these patients.

Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB).

Background: The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen. Methods: FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used. Results: Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28-51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, -7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02). Conclusions: In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.

Contrast enhanced ultrasound of carotid plaque in acute ischemic stroke (CUSCAS study).

INTRODUCTION: Carotid atherosclerosis represents 8 to 15% of ischemic strokes in relation to the concept of "vulnerable" plaque. Contrast enhanced ultrasound (CEUS) can detect moving microbubbles within the plaque corresponding to neovessels that constitute "precursors" of vulnerable plaque and intraplaque hemorrhage. CEUS was not studied specifically in acute ischemic strokes. The aim of this study is to analyse the prevalence of CEUS carotid plaque ipsilateral at the ischemic stroke as well as the main characteristics of contrast-plaques. METHOD: A single-centre prospective pilot study involving 33 consecutive patients with a stroke ≤10 days, diagnosed by an MRI with positive diffusion sequence and having a carotid plaque thickness ≥2.5mm with low or heterogeneous echogenicity, located in the ipsilateral carotid territory at the stroke. Plaque echogenicity was done by visual analysis and by measurement of the gray scale median (GSM). A transcranial Doppler monitoring was carried out in search of HITS. The contrast ultrasound was performed after 2.5 cc IV injection of SonoVue®. A video clip was recorded after injection which was used for interpretation by visual analysis in 3 grades, provided by two independent expert readers. RESULTS: The population consisted of 10 women and 23 men aged 73 on average. The topography of strokes in the carotid territory was located on the right in 11 (33%) cases and on the left in 22 (67%) cases. Seventeen patients had carotid stenosis between 0 and 49% according to the Nascet method and 16 patients had stenosis of 50 to 99%. The visual characterisation of the plaques had echolucent dominance (Type 1-2) in 18 cases and echogenic dominance (Type 3-4a) in 15 cases. Cardiovascular risk factors were common with no difference by sex. The inter-observer agreement of plaque enhancement was moderate in first reading (k=0.48) and excellent at consensus (k=0.91). Only one disagreement was found. Contrast agent enhancement of carotid plaque was observed in 11/32 patients, representing a prevalence of 34.4% - CI95% [17.9-50.9]. Variables associated with contrast plaque included the absence of antiplatelet drug (63.6% vs. 23.8%, P=0.05) and the presence of a regular edge on the plaque (91% vs. 48%, P=0.04). There was no difference in contrast enhancement for stenosis>or<50% in diameter and neither for the type of plaque. CONCLUSION: In a consecutive cohort of 33 patients, the prevalence of CEUS from an ipsilateral carotid plaque to a recent acute ischemic stroke was 34.4%. There was a statistically significant association between the contrast enhancement of the plaque and the absence of antiplatelet drug (P=0.05) and also the presence of a regular edge on the plaque (P=0.04). There was no correlation between plaque contrast and clinical and biological characteristics of patients or the presence of HITS.

A fuzzy logic decision support model for climate-driven biomass loss risk in western Oregon and Washington.

Dynamic global vegetation model (DGVM) projections are often put forth to aid resource managers in climate change-related decision making. However, interpreting model results and understanding their uncertainty can be difficult. Sources of uncertainty include embedded assumptions about atmospheric CO2 levels, uncertain climate projections driving DGVMs, and DGVM algorithm selection. For western Oregon and Washington, we implemented an Environmental Evaluation Modeling System (EEMS) decision support model using MC2 DGVM results to characterize biomass loss risk. MC2 results were driven by climate projections from 20 General Circulation Models (GCMs) and Earth System Models (ESMs), under Representative Concentration Pathways (RCPs) 4.5 and 8.5, with and without assumed fire suppression, for three different time periods. We produced maps of mean, minimum, and maximum biomass loss risk and uncertainty for each RCP / +/- fire suppression / time period. We characterized the uncertainty due to RCP, fire suppression, and climate projection choice. Finally, we evaluated whether fire or climate maladaptation mortality was the dominant driver of risk for each model run. The risk of biomass loss generally increases in current high biomass areas within the study region through time. The pattern of increased risk is generally south to north and upslope into the Coast and Cascade mountain ranges and along the coast. Uncertainty from climate future choice is greater than that attributable to RCP or +/- fire suppression. Fire dominates as the driving factor for biomass loss risk in more model runs than mortality. This method of interpreting DGVM results and the associated uncertainty provides managers with data in a form directly applicable to their concerns and should prove helpful in adaptive management planning.

A human-driven decline in global burned area.

Fire is an essential Earth system process that alters ecosystem and atmospheric composition. Here we assessed long-term fire trends using multiple satellite data sets. We found that global burned area declined by 24.3 ± 8.8% over the past 18 years. The estimated decrease in burned area remained robust after adjusting for precipitation variability and was largest in savannas. Agricultural expansion and intensification were primary drivers of declining fire activity. Fewer and smaller fires reduced aerosol concentrations, modified vegetation structure, and increased the magnitude of the terrestrial carbon sink. Fire models were unable to reproduce the pattern and magnitude of observed declines, suggesting that they may overestimate fire emissions in future projections. Using economic and demographic variables, we developed a conceptual model for predicting fire in human-dominated landscapes.

Simulation model of a laboratory-grown phreatophytic woody legume.

A mechanistic model was developed to simulate growth of mesquite Prosopis glandulosa Torr. trees under a phreatic (groundwater) moisture regime. Experimental data obtained in a greenhouse reproducing the phreatic environment (2 m soil columns with 10 cm of water-saturated soil at the bottom) were used to parameterize three submodels predicting carbon (C), nitrogen (N) and water dynamics in leaves, branches, roots and root nodules. In the column simulation model (COLSIM), photosynthesis was driven by air temperature and soil salinity. Water availability was nonlimiting. Nitrogen was absorbed by the roots from inorganic soil N and also fixed by root nodules. Comparison of the simulation with results from the greenhouse experiment showed that the model accurately reproduced shoot biomass and nitrogen content dynamics up to three years with or without a high soil salinity content. Root biomass was underestimated when soil salinity was high because the model did not account for the increased allocation of C to roots under conditions of high salinity. Observed annual cycles of water uptake during the three-year run were not reproduced because the model did not include a phenological function which apparently drives these cycles.