The new IMPACT 2002+ life cycle impact assessment methodology proposes a feasible implementation of a combined midpoint/damage approach, linking all types of life cycle inventory results (elementary ...flows and other interventions) via 14 midpoint categories to four damage categories. For IMPACT 2002+, new concepts and methods have been developed, especially for the comparative assessment of human toxicity and ecotoxicity. Human Damage Factors are calculated for carcinogens and non-carcinogens, employing intake fractions, best estimates of dose-response slope factors, as well as severities. The transfer of contaminants into the human food is no more based on consumption surveys, but accounts for agricultural and livestock production levels. Indoor and outdoor air emissions can be compared and the intermittent character of rainfall is considered. Both human toxicity and ecotoxicity effect factors are based on mean responses rather than on conservative assumptions. Other midpoint categories are adapted from existing characterizing methods (Eco-indicator 99 and CML 2002). All midpoint scores are expressed in units of a reference substance and related to the four damage categories human health, ecosystem quality, climate change, and resources. Normalization can be performed either at midpoint or at damage level. The IMPACT 2002+ method presently provides characterization factors for almost 1500 different LCI-results, which can be downloaded at http://www.epfl.ch/impact
PCR-based viral RNA to confirm the diagnosis of SARS-CoV-2 infection has a sensitivity of around 70%. We report three cases of patients with negative initial PCR and CT scan lesions that led us to ...suspect COVID-19, but which one(s) are really COVID-19?
•Puumala virus is the most prevalent of the four types of hantaviruses found in Europe.•Puumala virus is responsible for nephropathia endemic, a mild form of hemorrhagic fever with renal syndrome.•A ...severe bradycardia can occur during a Puumala virus infection.
Puumala orthohantavirus (PUUV) is the most prevalent of the four species of zoonotic hantaviruses found in Europe, causing nephropathia epidemica, a mild form of hemorrhagic fever with acute kidney injury that presents with elevated serum creatinine level, proteinuria and hematuria. The febrile phase of the infection begins with flu-like syndrome and visual disturbance. Laboratory results can show thrombocytopenia. The oliguric phase with elevated serum creatinine level then occurs. Cardiac involvement is sometimes observed, especially ECG abnormality: transient T-waves inversion, generally in the lateral or inferior leads. Marked bradycardia has been exceptionally described. We report the case of a 36-year-old woman with acute PUUV infection. Two days after admission, the patient presented a sinus bradycardia at 25/min. The bradycardia was asymptomatic, persisted one week and resolved spontaneously. Cardiac involvement in Puumala virus infection seems not to be associated with a bad prognosis. Bradycardia in the course of an influenza-like illness in endemic areas should suggest several pathogens such as legionella, Q fever or PUUV virus infection.
Data regarding the use of direct oral anticoagulants (DOACs) for the treatment of acute pulmonary embolism (PE) are sparse. We conducted a prospective multicentre registry study to describe patterns ...of DOAC prescription for the treatment of acute PE, and the associated risk of 6-month adverse events in daily practice.
We included all PE patients discharged since the availability of DOACs for the dedicated indication of acute PE treatment. Clinical data and 6-month outcomes, including death, recurrent venous thromboembolism (VTE), bleeding, and chronic thromboembolic pulmonary hypertension (CTEPH) were recorded prospectively. Temporal trends in DOAC prescription were tested.
Between 09/2012 and 04/2017, 1082 patients were included: 60.6% (n = 656) were treated with DOACs and 39.4% (n = 426) with another anticoagulant. The prescription rate of DOACs increased sharply just after their release on the market to reach a plateau over time, between 56% and 72% of the total prescription per year in PE patients (p for trend = 0.33). Active malignancy and renal function impairment were factors independently associated with non-prescription of DOACs. Overall, prescription of DOACs was appropriate in 95.3% of patients. The rate of use of non-recommended DOAC doses was 4.2% (n = 28). The rate of death, recurrent VTE, bleeding and CTEPH were 2.4%, 1.2%, 7.2%, and 1.9%, respectively in the DOAC group.
The choice to prescribe DOACs or not is related to patient characteristics. The overall appropriateness of prescription is high, while the rate of adverse events observed in patients treated with DOAC is low in our registry.
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•The prescription rate of DOACs reached sharply a plateau over time, between 56% and 72% of the total prescriptions per year in PE patients•Active malignancy and renal function impairment were factors associated with non-prescription of DOACs for the treatment of PE•Prescription of DOACs was inappropriate in 4.7% (non-recommended dose: 4.2%); prescription with severe kidney disease: 0.5%•The rates of death, recurrent VTE, bleeding and CTEPH were 2.4%, 1.2%, 7.2%, and 1.9%, respectively in patients treated with a DOAC
Dose adjustment of direct oral anticoagulants (DOACs) is not required in the setting of acute PE treatment according to the manufacturer’s labelling, beyond the contraindication in severe renal ...insufficiency. We designed a prospective, multicenter cohort study to investigate the impact of prescription of non-recommended DOAC doses on 6-month adverse events. The primary endpoint was a composite of all-cause death, recurrent VTE, major bleeding, and chronic thromboembolic pulmonary hypertension (CTEPH). In total, among 656 patients discharged with DOACs between 09/2012 and 10/2016, 28 (4.3%) were not treated with a recommended DOAC dose. All the non-recommended DOAC dose prescriptions were under-dosed according to the drug labelling. After multivariate adjustment, age > 70 years, a history of coronary artery disease, creatinine clearance < 50 mL/min and concomitant aspirin therapy were independently associated with non-recommended DOAC dose prescription (C-statistic: 0.82; Hosmer Lemeshow test: 0.50). The primary composite endpoint occurred in 7/28 patients (25.0%) in the non-recommended dose group and in 38/628 patients (6.1%) in the recommended dose group, yielding a relative risk of 3.19 in the non-recommended dose group (95% CI 1.16–8.70; p < 0.001). The higher primary endpoint rate observed in the non-recommended dose group was driven by a significantly higher rate of major bleeding (7.1 vs. 1.4%; p = 0.008), with a non-significant trend toward a higher rate of death (7.1 vs. 2.2%; p = 0.23), recurrent VTE (3.6 vs. 1.4%; p = 0.31), and CTEPH (7.1 vs. 1.6%; p = 0.32). In conclusion, empiric dose reduction of DOACs was associated with 6-month adverse events in our real-life registry.
Evidence-based clinical practice guidelines define initial management of acute pulmonary embolism (PE) according to risk stratification for early death.
The aims of the present study were to ...investigate patterns of non-compliance with guidelines for the acute PE treatment, and the associated risk of adverse events.
We performed an observational, multicentre, cohort study of acute PE. Inclusion criteria were all patients with pulmonary embolism admitted to the participating centres between January 2011 and April 2017. The measure of 100% compliance was used to allocate patients in the compliant or non-compliant groups. The primary outcome was all-cause death at 6 months. Secondary outcomes included recurrent venous thromboembolism and major bleeding.
In total, 1285 patients were included. Treatment was not in compliance with the guidelines in 172 patients (13.4%). Four factors were identified to be related to non-compliance with the guidelines: shock or hypotension (relative risk RR 5.23, 95% confidence interval CI 2.64–10.30; P<0.001), renal insufficiency (RR 1.80, 95% CI 1.41–2.28; P<0.001), active cancer (RR 1.35, 95% CI 1.24–1.48; P<0.001) and right ventricular dysfunction at admission (RR 1.06, 95% CI 1.01–1.11; P=0.01). The primary endpoint of all-cause death at 6 months occurred in 62 of 172 patients (36.0%) in the non-compliant group and in 131 of 1113 patients (11.8%) in the compliant group (hazard ratio 2.02, 95% CI 1.45–2.81; P<0.001). The rates of recurrent venous thromboembolism (8.7% vs 1.1%; P<0.001) and major bleeding (13.4% vs 4.9%, P=0.04) from admission to 6-month follow-up were higher in the non-compliant group.
Non-compliance with guidelines was independently associated with worse outcomes, including death, recurrent venous thromboembolism and bleeding.
Les recommandations des sociétés savantes internationales définissent la prise en charge des embolies pulmonaires (EP) aiguës selon la stratification du risque de mortalité aiguë.
Les objectifs de notre étude étaient d’étudier les conditions de non-compliance aux recommandations pour le traitement des EP aiguës, ainsi que le risque associé de survenu d’évènement clinique.
Nous avons réalisé une étude observationnelle, multicentrique, prospective d’une cohorte d’EP aiguë. Les critères d’inclusions étaient toutes les EP admises dans les centres participant entre janvier 2011 et avril 2017. L’évaluation de la compliance aux recommandations étaient faîtes sur la base de la loi du tout ou rien. Le critère primaire de jugement était la mortalité toute cause à 6 mois. Les critères secondaires étaient les récidives de maladie thromboembolique veineuse (MTEV) et les saignements majeurs.
Au total, 1285 patients ont été inclus. Le traitement de l’EP n’était pas en accord avec les recommandations chez 172 patients (13,4 %). Nous avons identifié 4 facteurs associés à la non-compliance aux recommandations : l’existence d’une hypotension artérielle ou d’un état de choc (risque relatif RR 5,23, intervalle de confiance à 95 % IC 2,64–10,30 ; p<0,001), une altération de la fonction rénale (RR 1,80, IC 95 % 1,41–2,28 ; p<0,001), un cancer actif (RR 1,35, IC 95 % 1,24–1,48 ; p<0,001) et une dysfonction ventriculaire droite à l’admission (RR 1,06, IC 95 % 1,01–1,11 ; p=0,01). Le critère primaire, décès toute cause à 6 mois est survenu chez 62 patients du groupe non compliant (36,0 %) et chez 131 patients du groupe compliant (11,8 %) avec un risque relatif de 2,02 pour le groupe non compliant (IC 95 % 1,45–2,81 ; p<0,001). Au cours du suivi, les taux de survenu des récidives de MTEV (8,7 % vs 1,1 % ; p<0,001) et de saignement majeur (13,4 % vs 4,9 %, p=0,04) étaient plus élevés dans le groupe non compliant comparativement au groupe compliant.
Dans notre, étude, la non-compliance aux recommandations étaient associée à un sur-risque de décès, de récidive de MTEV et de saignement.
Sjögren’s syndrome is well known to target exocrine glands, especially lacrimal and salivary glands, which share with mammary glands anatomical, histological, and immunological features. Herein, we ...investigated the mammary involvement in patients with Sjögren’s syndrome and compared the histological findings with minor salivary gland involvement. We reviewed the charts of patients with Sjögren’s syndrome (followed in Montpellier University Hospital, between January 2000 and January 2015), in whom minor salivary gland and mammary tissues were available. Two expert pathologists analysed retrospectively these tissues in order to identify inflammatory patterns. Immunohistochemical stainings were performed to precise leucocyte distribution. Sixteen Sjögren’s syndrome patients with available salivary and breast tissue samples were included. All were women, with a median age of 60.1 ± 11.3 years at Sjögren’s syndrome diagnosis. Mammary biopsy was conducted because of breast symptoms in 6 patients and following imaging screening strategies for breast cancer in 10 patients. Nine patients exhibited an inflammatory breast pattern (lymphocytic infiltrates or duct ectasia), close to minor salivary gland histological findings. Immunohistochemical stainings (
n
= 5) revealed B and T cell infiltrates within breast tissue, with a higher proportion of T CD4+ cells, but no IgG4-secreting plasma cells were found. This is the first series to describe breast inflammatory patterns in Sjögren’s syndrome. Mastitis is in line with the classical involvement of exocrine glands in this disease. These findings are consistent with the literature data considering Sjögren’s syndrome as an “autoimmune epithelitis”.
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating ...auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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