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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. Patients and methods We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). Results Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4–10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n = 50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9 mg/L vs 46.2 mg/L). Conclusion This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.

International audience; We conducted a retrospective Covid-clinic-Toul cohort study at Toulouse university hospital, in southern France (2800 beds, tertiary hospital covering an area of about 3 million inhabitants) and selected hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from September 1st, 2020 to October 31st, 2020. We compared their demographics, clinical, biological and radiological features, as well as unfavorable outcome (admission in an intensive care unit, mechanical ventilation, death) at Day 14 after admission to those of hospitalized patients during the 1st wave (March 11, 2020 to April 20, 2020).

Objectives To describe the frequency of QuantiFERON-TB Gold in-tube test® (QFT-GIT) indeterminate results due to no response to phytohaemagglutinin A stimulation in the control tube in vasculitis patients prior to immunosuppressant therapy; and to compare it with other groups of patients. Methods This was a single-centre, retrospective study. Patients and controls were included between 1 January 2008 and 31 December 2015. We assessed the rate of indeterminate results of the QFT-GIT in 38 patients with systemic vasculitis prior to any corticosteroid or immunosuppressant therapy, compared with 40 non-vasculitis patients with biological inflammatory syndrome, and 310 non-immunosuppressed patients matched for gender and age. Results Indeterminate results due to no response to phytohaemagglutinin A were more frequent in vasculitis patients (21.1%) compared with non-vasculitis patients with biological inflammatory syndrome (7.5%) (Fisher's exact test: P = 0.11) and to anonymized controls (7%) (P = 0.009). Responses to phytohaemagglutinin A were significantly lower in vasculitis patients compared with other groups (Kruskal–Wallis test: P < 0.0001) and compared with non-vasculitis patients with biological inflammatory syndrome (P = 0.0015). The multivariable analysis identified as independent predictors of an indeterminate result of the QFT-GIT: the presence of systemic vasculitis (odds ratio 9.64 [1.14–81.3], P = 0.037) and a high neutrophil-to-lymphocyte ratio (odds ratio 1.70 [1.21–2.37], P = 0.002). One patient with an indeterminate result of QFT-GIT developed active tuberculosis after one year of corticosteroid therapy for giant cell arteritis. Conclusion Our results question the reliability of QFT-GIT to rule out latent tuberculosis in vasculitis patients at diagnosis, prior to immunosuppressant therapy.

Background:Ear chondritis is often considered the pathognomonic feature of relapsing polychondritis (RP). Although painful redness and swelling of the pinna and a resultant cauliflower ear are universally recognized as chondritis, the complete spectrum of symptoms associated with ear chondritis have not been well described.Objectives:The study objective was to seek patient input to help characterize ear chondritis An online survey was administered in English or Spanish to participants with self-reported RP.Methods:Participants were asked questions about their ear pain, including quality, location, duration, aggravating/alleviating factors, timing of onset and duration. Participants were included who reported age ≥ 18 years, a diagnosis of RP confirmed by a physician, and sufficient symptoms to meet McAdams or Damiani’s diagnostic criteria. Participants were categorized as having “typical ear chondritis” if they reported ear pain localized to the pinna with associated redness and swelling. Atypical presentations of ear chondritis were also considered.Results:A total of 685 participants from five continents completed the survey. Among them, 659 met inclusion criteria for subsequent analysis. Most participants were female (n=574; 87%), white (n=548; 83%) and from the United States (n=484;74%). The median age was 50 years (interquartile range = 41-58). In total, 593 (90%) patients reported ear pain, 227 (38%) had “typical ear chondritis”, and 98 (16%) had cauliflower ear.Ear pain was most commonly described as burning (n=334, 56%) or throbbing (n=295, 50%). The most common location of pain was the pinna (n=373, 63%). Participants reported ear redness (n=454, 60%) and swelling (n=405, 62%). Some patients experienced only ear redness without swelling (n=286, 48%) or only ear swelling without redness (n=71, 12%). The most common aggravating factors were minor trauma (n=371, 62%) and stress (n=358, 60%). The most common alleviating factor was avoidance of touching the ear (n=374, 63%). Pain was most frequently reported during the daytime (n=355, 60%) and most likely to occur in either ear at different times (n=310, 52%). Onset could be gradual (n=198, 33%) or sudden (n=155, 26%). Pain typically lasted a few hours (n=175, 30%) or 2-3 days (n=130, 22%). The majority of patients who had pinna pain also had pain in other parts of the ear (e.g. mastoid process, inner ear, whole ear) at some point (n=394, 67%). In patients with cauliflower ear, the most common location of pain was the pinna (n=57, 58%) followed by pain inside the ear (n=53, 54%). Most participants reported at least two different types of pain (n=420, 64%).Conclusion:Ear chondritis in patients with RP has a wide range of clinical presentations and characteristics beyond the typical triad of redness, swelling, and pain localized to the pinna. The description of pain often significantly varies within the same patient. Knowledge of the various distinct characteristics of ear involvement in RP may help physicians recognize and monitor the disease more effectively.Disclosure of Interests:None declared

International audience; Essentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 109 L-1 and < 10 × 109 L-1 . Exposure to anticoagulants was a major risk factor of severe bleeding.Summary: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the Cytopénies Auto-immunes Registre Midi-PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L-1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L-1 versus ≥ 20 × 109 L-1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 109 L-1 and 19 × 109 L-1 versus ≥ 20 × 109 L-1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 109 L-1 and < 10 × 109 L-1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.

Clinical evaluation of drugs before approval is based on the experimental design of clinical trial with randomization of drug exposure. Unfortunately, conclusions of clinical trials are necessarily limited to patients enrolled in the trial. It is therefore necessary to compare these experimental data from clinical trials with the real use of drugs in clinical practice. Pharmacoepidemiology is defined as the study in real conditions and on large populations, of use, effectiveness and risk of drugs. The methods and fields of application of pharmacoepidemiology are described. They allow to characterize conditions of use, misuse, clinical effectiveness, adverse drug reactions and risks of drugs. The development of pharmacoepidemiology should allow optimization of "rational use" of drugs.

Resume Introduction Une pathologie thymique, benigne ou maligne, peut accompagner les pathologies auto-immunes. Si elle est plus frequente en cas de myasthenie, de neuromyotonie ou encore d’erythroblastopenie, elle peut se rencontrer dans presque toutes les maladies auto-immunes. Observation Nous rapportons la premiere description, a notre connaissance, d’une association entre un thymome malin et un syndrome de Reynolds (definie par la presence d’une cirrhose biliaire primitive et d’une sclerodermie). Conclusion L’hypothese physiopathologique avancee est un echappement thymique de lymphocytes T autoreactifs a l’origine de la pathologie auto-immune dans ce contexte de syndrome auto-immun multiple.

Background Romiplostim and eltrombopag, the two marketed thrombopoietin receptor agonists (TPO-RAs), have distinct binding sites and might have distinct pharmacodynamic mechanisms. The aim of this study was to compare their adverse drug reaction (ADR) patterns. Methods We selected in the French PharmacoVigilance Database all ADRs associated with TPO-RAs from TPO-RA marketing until the 31st of December 2013. Medical charts were reviewed. We conducted disproportionality analyses comparing romiplostim exposure in the reports of a given ADR pattern (thrombosis, neurological, cutaneous, gastrointestinal or hematological) to romiplostim exposure in all other TPO-RA-related ADR reports. Reporting Odds Ratios (RORs) were adjusted for age and gender. We also compared the number of reports of a given ADR pattern per million daily defined doses (DDDs) dispensed in France during the study period. Results We described 45 reports (53 ADRs) with romiplostim and 26 reports (37 ADRs) with eltrombopag. There were 19 venous thromboses. At least one other risk factor was present in 83.3% of the cases. Ten (55.6%) patients had been splenectomized previously. There were eight arterial thromboses. Another risk factor was noticed in all cases. There was no signal for an excess risk of thrombosis with romiplostim versus eltrombopag (ROR: 1.45, 95% CI [0.48–4.45]). There was a signal for a higher risk of gastrointestinal ADRs with eltrombopag (ROR: 30.28, 95% CI [3.23–383.86]) and of hematological ADRs with romiplostim (ROR: 14.36, 95% CI [1.73–119.08]). Dispensing data-adjusted comparisons led to similar results. Conclusions This study suggests different ADR patterns between romiplostim and eltrombopag.

Resume Introduction La pericardite est un mode de revelation rare de la maladie de Horton. Nous rapportons deux nouveaux cas. Observations Un homme et une femme de plus de 70 ans etaient hospitalises pour douleur thoracique. Le diagnostic retenu etait celui de pericardite confirmee par l’echocardiographie. Le syndrome inflammatoire etait marque. L’interrogatoire retrouvait a posteriori des signes cephaliques de maladie de Horton. Les biopsies d’artere temporale etaient caracteristiques de la maladie. Le traitement par prednisone (20 mg/j) permettait une remission complete, rapide et sans rechute clinique ulterieure de la pericardite, avec respectivement un an et trois ans de suivi. Conclusion La maladie de Horton doit etre discutee et recherchee cliniquement en cas de pericardite chez le sujet âge car la corticotherapie s’impose afin de prevenir les complications vasculaires de cette maladie. Sous corticoides, il n’a jamais ete rapporte de tamponnade ni d’evolution vers la constriction.

For software, there exists a community that can provide awareness and elements to justify the adoption of good engineering practices. For systems engineering, all this work is still to be done. This paper provides a modest contribution to such an endeavor, and more precisely in the area of requirements engineering for small systems. The targeted goals for this article are: Is model-driven requirements engineering, as practiced for large systems, relevant to develop small systems ? In which way can requirements engineering return on investment be demonstrated ? Are many of the assumptions made against documentation and model-based requirements engineering valid ? These issues are investigated in the context of the FRUITS experiment that aimed at comparing documentation-driven and model-driven requirements engineering. This experiment was carried out in 1998 by the systems department of MTI (Matra Transport International), a railway system provider. And Objectif Technologie provided some support to carry it out.

Statin use has been advocated to prevent atheromatous complications in lupus patients and may be widely prescribed for these patients in future. Statin-induced lupus has also been described, though the risk is not confirmed. The goal of this study was to detect a safety signal regarding statin-induced lupus. We conducted a case/non-case study in the French PharmacoVigilance Database from January 2000 until December 2010. Cases were drug-induced lupus reports. Non-cases were all reports of other adverse drug reactions (ADRs). Exposure to statins at the time of ADR was screened in each report. Among 235,147 ADR reports, 232 were drug-induced lupus. Exposure to statins was present in 17 (7.3%) cases and in 10,601 (4.7%) non-cases. Reporting odds ratio (ROR) for statin exposure associated with lupus erythematosus was 1.67 (95% confidence interval 1.02–2.74). The ROR was > 1 for each statin but fluvastatin. This pharmacoepidemiological study suggests a link between statin exposure and lupus induction. The benefit-to-risk ratio of statin therapy in lupus patients should be evaluated through randomized controlled trials.

Introduction Plusieurs cas de thrombopénie immunologique (PTI) de novo ont été décrits après vaccination anti-SARS-CoV2. Chez les patients avec un PTI, le risque de rechute ou d’aggravation secondaire à une vaccination anti-SARS-CoV2 reste mal connu. Patients et méthodes Nous avons conduit une étude observationnelle multicentrique dans 5 centres français. Les patients adultes ayant un diagnostic de PTI (primaire ou secondaire) selon les critères internationaux et pris en charge dans l’un de ces centres ont été inclus s’ils avaient reçu au moins une injection de vaccin anti- SARS-CoV2 entre janvier et août 2021. Les patients sans chiffre plaquettaire disponible dans les 3 mois précédant le vaccin ou dans les 3 mois suivants le vaccin ont été exclus. Tous les patients étaient inclus dans le registre prospectif CARMEN-France et ne s’étaient pas opposés à une collection des données en vie réelle. Les données cliniques et biologiques étaient recueillies avec un formulaire standardisé, et le suivi était limité à 3 mois après la première injection vaccinale. Résultats Entre janvier et août 2021, 195 patients adultes avec un diagnostic de PTI (61 % femmes), d’âge médian 65 ans (IQR 49-74) ont reçu au moins une dose de vaccin anti-SARS-CoV2. La durée médiane d’évolution du PTI était de 73 mois (IQR 28-134) à la première dose de vaccin, 170 (87 %) patients avaient un PTI primaire, et 89 (46 %) n’avaient aucun traitement au moment de la vaccination. La durée médiane de suivi était de 62 jours (IQR 43-90) après la première injection de Tozinameran (Cominarty®; n = 167, 86 %), ChadOx1nCoV-19 (Vaxzevria®; n = 16, 8 %), mRNA-1273 Moderna (Spikevax®; n = 11, 6 %) ou Ad26.COV2-S (Covid-19 vaccine Janssen®; n = 1, 1 %). Parmi les 195 patients, 129 (66 %) avaient eu un hémogramme à 7± 3 jours après la première injection avec une médiane de plaquettes à 118 G/L (IQR 70-192; plaquettes