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  1. Article ; Online: Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate.

    Pradelle, Alexiane / Mainbourg, Sabine / Provencher, Steeve / Massy, Emmanuel / Grenet, Guillaume / Lega, Jean-Christophe

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2024  Volume 171, Page(s) 116055

    Abstract: Background: During the first wave of COVID-19, hydroxychloroquine (HCQ) was used off-label despite the absence of evidence documenting its clinical benefits. Since then, a meta-analysis of randomised trials showed that HCQ use was associated with an 11% ...

    Abstract Background: During the first wave of COVID-19, hydroxychloroquine (HCQ) was used off-label despite the absence of evidence documenting its clinical benefits. Since then, a meta-analysis of randomised trials showed that HCQ use was associated with an 11% increase in the mortality rate. We aimed to estimate the number of HCQ-related deaths worldwide.
    Methods and findings: We estimated the worldwide in-hospital mortality attributable to HCQ use by combining the mortality rate, HCQ exposure, number of hospitalised patients, and the increased relative risk of death with HCQ. The mortality rate in hospitalised patients for each country was calculated using pooled prevalence estimated by a meta-analysis of published cohorts. The HCQ exposure was estimated using median and extreme estimates from the same systematic review. The number of hospitalised patients during the first wave was extracted from dedicated databases. The systematic review included 44 cohort studies (Belgium: k = 1, France: k = 2, Italy: k = 12, Spain: k = 6, Turkey: k = 3, USA: k = 20). HCQ prescription rates varied greatly from one country to another (range 16-84%). Overall, using median estimates of HCQ use in each country, we estimated that 16,990 HCQ-related in-hospital deaths (range 6267-19256) occurred in the countries with available data. The median number of HCQ-related deaths in Belgium, Turkey, France, Italy, Spain, and the USA was 240 (range not estimable), 95 (range 92-128), 199 (range not estimable), 1822 (range 1170-2063), 1895 (range 1475-2094) and 12739 (3244- 15570), respectively.
    Conclusions: Although our estimates are limited by their imprecision, these findings illustrate the hazard of drug repurposing with low-level evidence.
    MeSH term(s) Humans ; Hydroxychloroquine ; COVID-19 ; Compassionate Use Trials ; COVID-19 Drug Treatment ; Treatment Outcome
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH)
    Language English
    Publishing date 2024-01-02
    Publishing country France
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2023.116055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Association between immune-related adverse events and prognosis in patients treated with immune checkpoint inhibitors in melanoma: A surrogacy analysis.

    Euvrard, Romain / Robert, Marie / Mainbourg, Sabine / Dalle, Stéphane / Lega, Jean-Christophe

    Fundamental & clinical pharmacology

    2023  Volume 38, Issue 2, Page(s) 369–379

    Abstract: Background: Immune checkpoint inhibitors (ICI) represent a breakthrough in oncology in terms of prognosis and safety. They now constitute a cornerstone in the management of metastatic melanoma. However, a new kind of adverse event called immune-related ... ...

    Abstract Background: Immune checkpoint inhibitors (ICI) represent a breakthrough in oncology in terms of prognosis and safety. They now constitute a cornerstone in the management of metastatic melanoma. However, a new kind of adverse event called immune-related adverse events (irAE) has emerged. These irAE could be conceptually considered as an indicator of the antitumoral immune response, but the association between irAE and prognosis is still a matter of debate.
    Objective: The purpose of this study was to investigate the association between the overall survival (OS) and the prevalence of irAE in melanoma.
    Methods: MEDLINE/PubMed, WebofScience, ClinicalTrials, and WHOTrials databases were searched to identify phase 3 randomized controlled trials (RCT) assessing ICI in melanoma and published up to April 2021. A weighted regression was performed to estimate this association according to standard method of surrogacy analysis.
    Results: A total of 14 RCT including 7646 patients (median age: 59.3 years) with melanoma were included. All types of ICI were represented (ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, as well as ipilimumab and nivolumab combination). irAE were frequent but rarely fatal. The combination of ICI caused more irAE than anti-PD1 (or PDL1) and anti-CTLA4 monotherapies. No relationship was found between the occurrence of irAE and OS (beta coefficient 0.078, R
    Conclusion: Although limited by the heterogeneity of ICI included in the regression and the low number of included RCT, the present study suggests an absence of association between irAE and prognosis in melanoma.
    MeSH term(s) Humans ; Middle Aged ; Melanoma/drug therapy ; Nivolumab/adverse effects ; Ipilimumab/adverse effects ; Immune Checkpoint Inhibitors/adverse effects ; Prognosis ; Retrospective Studies
    Chemical Substances Nivolumab (31YO63LBSN) ; Ipilimumab ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 639134-5
    ISSN 1472-8206 ; 0767-3981
    ISSN (online) 1472-8206
    ISSN 0767-3981
    DOI 10.1111/fcp.12966
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Treatment strategy for acquired pure red cell aplasia: a systematic review and meta-analysis.

    Lobbes, Hervé / Lega, Jean-Christophe / Le Guenno, Guillaume / Ruivard, Marc / Mainbourg, Sabine

    Blood advances

    2023  Volume 7, Issue 21, Page(s) 6451–6465

    Abstract: The treatment of autoimmune acquired pure red cell aplasia (aPRCA) is challenging. Guidelines are based on expert recommendations in the absence of controlled trials. We assessed the efficacy of the main treatment strategy through a systematic review and ...

    Abstract The treatment of autoimmune acquired pure red cell aplasia (aPRCA) is challenging. Guidelines are based on expert recommendations in the absence of controlled trials. We assessed the efficacy of the main treatment strategy through a systematic review and meta-analysis using MEDLINE, EMBASE, and the Cochrane Library up to September 2022. The overall response rate (ORR) was pooled using random-effects models. In total, 24 observational studies (19 retrospective, median follow-up of 48 months) encompassing 753 patients (49% male) were included. Primary aPRCA represented 57% of the cases. The risk of bias was moderate to high using the ROBINS-I tool. Substantial heterogeneity (I2 > 50%) was retrieved. Corticosteroids as monotherapy as first-line treatment (186 patients, 13 studies) provided an ORR of 47% (95% confidence interval [CI], 34-60). Cyclosporine A was the most frequently used immunosuppressant agent (384 patients, 18 studies), providing an ORR of 74% (95% CI, 66-82) with a similar ORR in first- (73%) and second-line (76%) treatment and when cyclosporin was used as monotherapy (83%) or with corticosteroids (77%). A total of 112 patients (10 studies) received cyclophosphamide, with an ORR of 49% (95% CI, 35-64), which was higher when cyclophosphamide was combined with corticosteroids (48%) and used in second-line treatment (58%) than in monotherapy (31%), and in first-line treatment (44%). Sirolimus use was reported only after cyclosporine A failure and provided an ORR of 87% (95% CI, 68-100; 64 patients, 3 studies). Substantial uncertainty remains regarding the best treatment strategy in the absence of high-quality evidence. This study was registered on the PROPERO database as #CRD42022360452.
    MeSH term(s) Humans ; Adrenal Cortex Hormones/therapeutic use ; Cyclophosphamide ; Cyclosporine ; Red-Cell Aplasia, Pure/drug therapy ; Red-Cell Aplasia, Pure/etiology ; Retrospective Studies
    Chemical Substances Adrenal Cortex Hormones ; Cyclophosphamide (8N3DW7272P) ; Cyclosporine (83HN0GTJ6D)
    Language English
    Publishing date 2023-08-27
    Publishing country United States
    Document type Meta-Analysis ; Systematic Review ; Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Prevention of venous thromboembolism in nephrotic syndrome: the quest towards precision medicine.

    Lobbes, Hervé / Mainbourg, Sabine / Lega, Jean-Christophe

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2020  

    Language English
    Publishing date 2020-12-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfaa337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Analysis of incidence of thrombotic complications in the presence of competing risks.

    Mainbourg, Sabine / Cucherat, Michel / Lega, Jean-Christophe

    Thrombosis research

    2020  Volume 191, Page(s) 152

    MeSH term(s) Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Critical Illness ; Humans ; Incidence ; Intensive Care Units ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Language English
    Publishing date 2020-05-03
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2020.04.045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Extra-respiratory comorbidities and transplantation in the French cystic fibrosis registry.

    Mainbourg, Sabine / Durieu, Isabelle / Dehillotte, Clémence / Reynaud, Quitterie

    Expert review of respiratory medicine

    2019  Volume 13, Issue 8, Page(s) 799–802

    Abstract: ... ...

    Abstract Background
    MeSH term(s) Adult ; Comorbidity ; Cystic Fibrosis/epidemiology ; Cystic Fibrosis/surgery ; Diabetes Mellitus ; Female ; France/epidemiology ; Humans ; Kidney Failure, Chronic ; Lung Transplantation ; Male ; Osteoporosis ; Registries
    Language English
    Publishing date 2019-07-03
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Observational Study
    ZDB-ID 2479146-5
    ISSN 1747-6356 ; 1747-6348
    ISSN (online) 1747-6356
    ISSN 1747-6348
    DOI 10.1080/17476348.2019.1638768
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis.

    Desaintjean, Charlene / Ahmad, Kaïs / Traclet, Julie / Gerfaud-Valentin, Mathieu / Durel, Cecile-Audrey / Glerant, Jean-Charles / Hot, Arnaud / Lestelle, François / Mainbourg, Sabine / Nasser, Mouhamad / Seve, Pascal / Turquier, Ségolène / Devouassoux, Gilles / Cottin, Vincent

    Frontiers in medicine

    2024  Volume 11, Page(s) 1341310

    Abstract: Introduction: Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting ... ...

    Abstract Introduction: Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.
    Objective: Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under "real-world" conditions.
    Methods: This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.
    Results: Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (
    Conclusion: In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.
    Language English
    Publishing date 2024-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2024.1341310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Extreme Hyperferritinemia: Causes and Prognosis.

    Fauter, Maxime / Mainbourg, Sabine / El Jammal, Thomas / Guerber, Arthur / Zaepfel, Sabine / Henry, Thomas / Gerfaud-Valentin, Mathieu / Sève, Pascal / Jamilloux, Yvan

    Journal of clinical medicine

    2022  Volume 11, Issue 18

    Abstract: The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/ ... ...

    Abstract The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.
    Language English
    Publishing date 2022-09-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm11185438
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Recurrent superficial vein thrombosis revealing relapsing polychondritis associated with myelodysplastic syndrome.

    Tabary, Axel / Lega, Jean-Christophe / Mainbourg, Sabine / Lobbes, Hervé

    Rheumatology (Oxford, England)

    2020  Volume 59, Issue 11, Page(s) 3581

    MeSH term(s) Aged, 80 and over ; Ear Auricle ; Ear Diseases/physiopathology ; Forearm/blood supply ; Humans ; Male ; Myelodysplastic Syndromes/diagnosis ; Polychondritis, Relapsing/diagnosis ; Polychondritis, Relapsing/physiopathology ; Venous Thrombosis/physiopathology
    Language English
    Publishing date 2020-05-27
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keaa185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Significant Major Bleeding in Hospitalized Patients with COVID-19 Receiving Thromboprophylaxis.

    Mai, Vicky / Mainbourg, Sabine / Tan, Boun Kim / Lega, Jean-Christophe / Provencher, Steeve

    Thrombosis and haemostasis

    2021  Volume 121, Issue 12, Page(s) 1670–1673

    MeSH term(s) Anticoagulants/adverse effects ; COVID-19 ; Hemorrhage/chemically induced ; Humans ; SARS-CoV-2 ; Venous Thromboembolism/epidemiology ; Venous Thromboembolism/prevention & control
    Chemical Substances Anticoagulants
    Language English
    Publishing date 2021-06-06
    Publishing country Germany
    Document type Letter ; Comment
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/a-1477-4027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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