Eighty percent of COPD patients experience dyspnea during activities of daily life (ADL). To the best of our knowledge, the Modified Medical Research Council (MMRC) dyspnea scale is the only ...validated scale designed to quantify dyspnea during ADL available in the French language. Two other instruments are only available in English versions: the London Chest Activity of Daily Living (LCADL) scale that allows a specific evaluation of dyspnea during ADL and the Dyspnea-12 questionnaire that evaluates the affective (emotional) and sensory components of dyspnea in daily life. The aim of this study was to translate and validate French versions of both LCADL and Dyspnea-12 questionnaires and to determine the reliability of these versions for the evaluation of dyspnea in severe to very severe COPD patients.
Both translation and cultural adaptation were based on Beaton's recommendations. Fifty consecutive patients completed the French version of LCADL and Dyspnea-12 and other questionnaires (MMRC, Saint George's Respiratory Questionnaire SGRQ, Hospital Anxiety and Depression HAD), at a 2-week interval. Internal consistency, validity, and reliability of LCADL and Dyspnea-12 were evaluated.
The French version of LCADL and Dyspnea-12 demonstrated good internal consistency with Cronbach's α of, respectively, 0.84 and 0.91. LCADL was correlated significantly with item activity of SGRQ (ρ=0.55,
<0.001), total score of SGRQ (ρ=0.63,
<0.001), item impact of SGRQ (ρ=0.57,
<0.001), and HAD-depression (HAD-D) (ρ=0.47,
=0.001); and Dyspnea-12 was correlated significantly with MMRC (ρ=0.39,
<0.001), HAD-anxiety (ρ=0.64,
<0.001), and HAD-D (ρ=0.64,
<0.001). The French version of LCADL and Dyspnea-12 demonstrated good test-retest reliability with, respectively, intraclass coefficient =0.84 (
<0.001) and 0.91 (
<0.001).
The French versions of LCADL and Dyspnea-12 questionnaires are promising tools to evaluate dyspnea in severe to very severe COPD patients.
Objective
Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been ...excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer.
Methods
A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response.
Results
The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation.
Conclusion
Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
Alveolar haemorrhage (AH) can be a mild or life-threatening manifestation of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), but its prognostic impact and specific ...characteristics remain controversial. Our objective was to determine the prognostic value of AH in this context.
AH episodes that occurred, between 1991 and 2010, in AAV patients entered in the FVSG database were retrospectively analysed. Data on AH characteristics and outcome measures were collected on a specific form.
Among the 80 cases analysed, AAV were 61.25% granulomatosis with polyangiitis (GPA) (Wegener), 26.25% microscopic polyangiitis (MPA), 10% Churg-Strauss syndrome and 2 (2.5%) unclassified. Mild or severe haemoptysis alone, or together with other clinical symptoms was present in 77 (96.2%) patients before AAV diagnosis. Among 10 (12.5%) patients requiring mechanical ventilation, 4 had prior minor haemoptysis before abundant AH. Sixty-one (76.3%) patients had concomitant active rapid crescentic glomerulonephritis causing renal insufficiency (pulmo-renal syndrome): 37/49 GPA (Wegener) (75.5% of all GPA (Wegener)), 19/21 MPA (90.4% of all MPA), 3/8 had CSS and 2/2 had unclassified vasculitis. The mean AH-to-treatment-onset interval was 5.9 days. Mean follow-up was 7.3 years. Forty-seven (58.8%) patients relapsed: 23 with AH and with (13) or without (10) other organ involvement, 24 with non-AH manifestation(s). Three patients underwent kidney transplantation. Sixteen (20%, 8 GPA (Wegener) and 8 MPA) patients died. No death resulted directly from the initial AH; 14 (87.5%) patients with pulmo-renal syndrome died.
As previously demonstrated by the Five-Factor Score, AH alone is not predictive of poor prognosis, unlike kidney involvement, which dictates a poor outcome.
Alpha1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis. Alpha1-antitrypsin (α1-AT) is the major inhibitor of proteinase 3 (PR3), the main target antigen of antineutrophil ...cytoplasm antibodies (ANCA) in Wegener's granulomatosis. α1-AT is encoded by a polymorphic gene, with over 75 alleles, defining severely, medium and non-deficient protease inhibitor (PI) phenotypes. We describe the association of severely and medium deficient PI phenotypes with anti-PR3 positive systemic vasculitis, and postulate a pathogenetic role for α1-AT deficiency and the occurrence of ANCA, with specificity for PR3 in a subgroup of patients with Wegener's granulomatosis.
The increasing number of cyclists, and the introduction of new infrastructure has created new ways for cyclists and other road users to interact, which may impact road safety. Consequently, our aim ...was to contribute to a better understanding of accidents involving cyclists through an in-depth, pre-accident analysis based on an activity-centred approach. Various pre-accident situations, judged as risky by twenty cyclists, were collected and classified as a function of their relative frequency of occurrence. The analysis found that a third of these situations involved interactions with pedestrians or other obstacles. Then, the most frequent situations are related to: (a) interactions with motorists either entering or leaving a parking space; (b) motorists who stepped in front of a cyclist when turning right; (c) cars entering the road from the right at an intersection, and (d) motorists squeezing cyclists off the road when overtaking. An analysis of situations where cyclists’ visibility was impaired found similar results except for situations (c) and (d) where cyclists’ visibility was very rarely engaged, and which both appeared to be associated to deliberate motorist behaviours. These findings point out the most frequent pre-accident situations reported by cyclists, and highlight the need for their better integration, as a new type of road user, in urban areas.
Le nombre grandissant de cyclistes et les évolutions des aménagements routiers associés induisent de nouvelles interactions entre cyclistes et autres usagers de la route. Compte tenu des enjeux sécuritaires, l’objectif poursuivi ici était de mieux comprendre les situations accidentogènes impliquant les cyclistes via une analyse détaillée de ces situations avec une méthodologie ergonomique fondée sur l’analyse de l’activité. Les différentes situations de pré-accident jugées comme risquées par vingt cyclistes lors de leur pratique habituelle ont été collectées et classées selon leur fréquence d’occurrence relative. Les résultats indiquent que près d’un tiers des situations de pré-accident rapportées résultent de l’interaction entre cyclistes et piétons. Après quoi et par ordre de fréquence, les situations étaient liées à des interactions avec des automobilistes (a) entrant ou quittant le stationnement, (b) interférant avec les cyclistes en tournant à droite, (c) interférant avec les cyclistes en venant de la droite à une intersection, (d) ou encore dépassant les cyclistes de trop près. Lorsque l’intérêt s’est porté plus spécifiquement sur les situations où la visibilité des cyclistes était engagée, des résultats similaires ont été obtenus exception faite des catégories (c) véhicule venant de la droite et coupant la trajectoire du cycliste et (d) dépassant les cyclistes de trop près qui tendent à disparaître. Ces situations (c & d) étaient majoritairement associées à des comportements délibérés des automobilistes. Dans leur ensemble, les résultats permettent de classer par fréquence d’apparition les situations de pré-accident rapportées par les cyclistes et pointent la nécessitée d’une meilleure intégration des usagers cyclistes en zone urbaine.
The dynamic derivatives are widely used in linear aerodynamic models in order to determine the flying qualities of an aircraft: the ability to predict them reliably, quickly and sufficiently early in ...the design process is vital in order to avoid late and costly component redesigns. This paper describes experimental and computational research dealing with the determination of dynamic derivatives carried out within the FP6 European project SimSAC. Numerical and experimental results are compared for two aircraft configurations: a generic civil transport aircraft, wing-fuselage-tail configuration called the DLR-F12 and a generic Transonic CRuiser, which is a canard configuration. Static and dynamic wind tunnel tests have been carried out for both configurations and are briefly described within this paper. The data generated for both the DLR-F12 and TCR configurations include force and pressure coefficients obtained during small amplitude pitch, roll and yaw oscillations while the data for the TCR configuration also include large amplitude oscillations, in order to investigate the dynamic effects on nonlinear aerodynamic characteristics. In addition, dynamic derivatives have been determined for both configurations with a large panel of tools, from linear aerodynamic (Vortex Lattice Methods) to CFD. This work confirms that an increase in fidelity level enables the dynamic derivatives to be calculated more accurately. Linear aerodynamics tools are shown to give satisfactory results but are very sensitive to the geometry/mesh input data. Although all the quasi-steady CFD approaches give comparable results (robustness) for steady dynamic derivatives, they do not allow the prediction of unsteady components for the dynamic derivatives (angular derivatives with respect to time): this can be done with either a fully unsteady approach i.e. with a time-marching scheme or with frequency domain solvers, both of which provide comparable results for the DLR-F12 test case. As far as the canard configuration is concerned, strong limitations for the linear aerodynamic tools are observed. A key aspect of this work are the acceleration techniques developed for CFD methods, which allow the computational time to be dramatically reduced while providing comparable results.
► The paper deals with experimental and numerical prediction of dynamic derivatives. ► Wind tunnel data for two civil transport aircraft configurations are analyzed. ► Results from vortex lattice methods, Euler and RANS solvers are compared. ► CFD methods are more accurate and robust than vortex lattice methods. ► Acceleration techniques such as frequency domain solvers are very efficient.
Le nombre grandissant de cyclistes et les évolutions des aménagements routiers associés induisent de nouvelles interactions entre cyclistes et autres usagers de la route. Compte tenu des enjeux ...sécuritaires, l’objectif poursuivi ici était de mieux comprendre les situations accidentogènes impliquant les cyclistes via une analyse détaillée de ces situations avec une méthodologie ergonomique fondée sur l’analyse de l’activité. Les différentes situations de pré-accident jugées comme risquées par vingt cyclistes lors de leur pratique habituelle ont été collectées et classées selon leur fréquence d’occurrence relative. Les résultats indiquent que près d’un tiers des situations de pré-accident rapportées résultent de l’interaction entre cyclistes et piétons. Après quoi et par ordre de fréquence, les situations étaient liées à des interactions avec des automobilistes (a) entrant ou quittant le stationnement, (b) interférant avec les cyclistes en tournant à droite, (c) interférant avec les cyclistes en venant de la droite à une intersection, (d) ou encore dépassant les cyclistes de trop près. Lorsque l’intérêt s’est porté plus spécifiquement sur les situations où la visibilité des cyclistes était engagée, des résultats similaires ont été obtenus exception faite des catégories (c) véhicule venant de la droite et coupant la trajectoire du cycliste et (d) dépassant les cyclistes de trop près qui tendent à disparaître. Ces situations (c & d) étaient majoritairement associées à des comportements délibérés des automobilistes. Dans leur ensemble, les résultats permettent de classer par fréquence d’apparition les situations de pré-accident rapportées par les cyclistes et pointent la nécessitée d’une meilleure intégration des usagers cyclistes en zone urbaine.
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