Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.<p></p> Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.<p></p> Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.<p></p> Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Épreuves de transition dans les Crêtes pré-ardennaises (CCPA) : Modes, configuration, assemblage, agencement...

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Connaissances variées à propos des risques liés aux pollutions. Faire avec les impacts du cadmium sur les sols, l'eau et les personnes à des époques différentes

International audienceThe paper addresses the different ways of knowing and living with heavy metal pollution through time. It discusses local knowledge about it as well as the work done by scientists to produce data and monitor it since the 1990s. Cadmium, for instance, is very toxic. It accumulates and cannot be eliminated easily by living organisms including humans. However, its chronic effects remain unnoticed unless proper tools are used to make them explicit. We argue that invisibilization is not only a natural property' of the substance but also depends on the way industrial nuisances were dealt with in the past

Controverses autour de la mise en évidence des pollutions du bassin industriel de Decazeville (Aveyron)

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La fabrication d'un héritage encombrant : les pollutions métallurgiques de Viviez (Aveyron)

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La mise en évidence controversée des pollutions du bassin industriel de Decazeville (Aveyron)

International audienceDecazeville in Aveyron (France) is a very old mining basin where from the 19th century on, several metallurgical factories settled. Some are still operating, 47 years after the closure of the last coal pit; most of the time, they have limited their activities while specialising in metal manufacturing and shaping, or the recycling of metallurgy scraps. The rich social history of the small twin cities of Decazeville and Viviez, ie. the development and closure of the mines and factories, as well as the struggles and strikes that came along have been well documented. However, very few scholars have addressed the issue of the industrial nuisances and the transformation which has impacted the cities and landscapes. Yet, the level of pollution generated by this industry is well known by the ecotoxicologists who study its effects on rivers all the way up to the Gironde estuary. High quantities of heavy metals, especially cadmium, have been scattered into the environment since the 19th century and are still mostly trapped in the sediments of the Riou Mort and Lot rivers. Nowadays, industrial processes have improved and most of the effluents are under control; nonetheless, the potential noxiousness of historical pollution remains able to affect large portions of territories with unequal vulnerabilities. The residents of the Decazeville basin were the first ones to be exposed to pollution, first and foremost to the smoke then to effluent that affected the surrounding soils and streams. Many of the testimonies that were collected during interviews mention appalingly bad smells, belongings corroded by acid rains or the decline of gardens and vegetation. Although it seems that beyond individual disapproval and compensation claims, no real public critique has emerged for a very long time. We had to wait until the local health services reacted, after being alerted by information about poor soil quality that started to circulate when a project for the remediation of an industrial wasteland was launched. Then, the questions of environmental pollution and human health were asked, generating huge controversy. An epidemiological survey was organised, arousing tensions between the different actors involved such as state and local administrative representatives, elected local representatives and the main industrial operator, a zinc manufacturer which was already engaging in remediation actions. The first results of this controversial survey were presented publicly in February 2010 in Viviez. However, we still don't know if the new information on cadmium contamination - which affects a small number of people significantly - will change the residents' relations with their industrial past and present and the related risks. This paper aims to question the production and circulation of knowledge on metallic pollution in a specific socio-historical context where city and industry are consubstantial. Our study broaches both long and short time periods i.e. it takes into account of the very historicity of the basin both in economic, political and social terms. Our objective is to show how metal pollution is thought about, measured, managed, contained and compensated at different times in history in relation to the knowledge that was available at the time. We investigate what blocked the production and circulation of knowledge about risks, whether expert or lay ones, as well as what were the effects of the framing of pollution as a risk either internalised or externalised. In conclusion, we discuss the way local residents talk about the industrial nuisances they had to suffer from and may express critiques despite the fact that they fear their territory could be reduced to this aspect