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1. Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19

Author

Charlotte Summers, Hanna Jung, Hikombo HITOTO, Giulio Giovanni Cavalli, Mark Pritchard, Susanne Gjeruldsen Dudman, Cornelius Rau, Yusing Gu, Obada Yousif, Benjamin Lefèvre, Jamel Ortoleva, Carlos Lumbreras, Yvelynne Kelly, Matthew Hall, Andreas Lind, Antonio Loforte, Aquiles Rodrigo Henríquez-Trujillo, Rafael Freitas de Oliveira Franca, Manuel Etienne, Daniel Alejandro Pérez Muñoz, Moirangthem Bikram singh, Sebastiano Maria Colombo, Agnieszka Ołdakowska, Malcolm Gracie Semple, Anders Benjamin Kildal, Tom Fletcher, Kalynn Kennon, Sarah Cormican, Ali AIT HSSAIN, Bernard CHOLLEY, Gianluigi Li Bassi, Hernando Torres-Zevallos, Luís Bento, Leanne Hays, Lara Absil, Roberto Roncon Albuquerque Jr, Maria Toki, Oksana Kruglova, Louise Sigfrid, Colin McCloskey, Eder Caceres, Jaques Sztajnbok, Sebastien Preau, Federico D'AMICO, Guillaume Louis, Nina Buchtele, Manuel Rosa-calatrava, Dorothy Breen, Christopher Green, Denise Battaglini, Jolanta Popielska, Helena Barrasa, Olivier Terrier, Jacky Suen, Hoi Ping Shum, Guillaume Martin-Blondel, Stella Rousset, Eric D'Ortenzio, Miguel Pedrera-Jiménez, Willem Dieperink, Ioannis Trontzas, Barbara Wanjiru Citarella, Shona Moore, Sofia Tejada, Abigail Beane, John Kenneth Baillie, Simone Piva, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medical Research Council (MRC), Group, ISARIC Clinical Characterisation, Hall, Matthew D [0000-0002-2671-3864], Merson, Laura [0000-0002-4168-1960], Apollo - University of Cambridge Repository, Hall, M., Baruch, J., Carson, G., Citarella, B. W., Dagens, A., Dankwa, E. A., Donnelly, C. A., Dunning, J., Escher, M., Kartsonaki, C., Merson, L., Pritchard, M. G., Wei, J., Horby, P., Rojek, A., Olliaro, P. L., and Durante-Mangoni, E

Subjects
Male, Outcome Assessment, global health, 0601 Biochemistry and Cell Biology, law.invention, law, Case fatality rate, Pandemic, Epidemiology, Outcome Assessment, Health Care, 80 and over, ISARIC Clinical Characterisation Group, Biology (General), Outcome Assessment, Health Care/statistics & numerical data, Child, Aged, 80 and over, General Neuroscience, COVID-19, ICU, SARS-CoV-2, epidemiology, hospitalisation, human, medicine, viruses, Adolescent, Adult, Aged, Child, Preschool, Female, Hospitalization, Humans, Infant, Intensive Care Units, Length of Stay, Middle Aged, Retrospective Studies, Young Adult, General Medicine, Intensive care unit, Length of Stay/statistics & numerical data, Cohort, Intensive Care Units/statistics & numerical data, Medicine, Global health, Human, Viruses, Research Article, COVID-19/therapy, medicine.medical_specialty, Health Care/statistics & numerical data, Coronavirus disease 2019 (COVID-19), QH301-705.5, Science, General Biochemistry, Genetics and Molecular Biology, Disease severity, Preschool, Hospitalization/statistics & numerical data, General Immunology and Microbiology, business.industry, SARS-CoV-2/pathogenicity, Health Care, Epidemiology and Global Health, Emergency medicine, Observational study, business
Abstract

Background:There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high dependency unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics.Methods:We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay.Results:Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors.Conclusions:Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly evolving situation.Funding:This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2021

2. High rate of indeterminate results of the QuantiFERON-TB Gold in-tube test, third generation, in patients with systemic vasculitis

Author

Laurent Sailler, G. Moulis, K. Paricaud, Grégory Pugnet, Antoine Blancher, Leonardo Astudillo, Emmanuel Treiner, Stella Rousset, Philippe Arlet, Bénédicte Puissant-Lubrano, CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Laboratoire d'Immunogénétique Moléculaire (LIMT)

Subjects
Male, diagnosis, latent tuberculosis infection, phytohemagglutinins, Interferon gamma release assay, Gastroenterology, vasculitis, 0302 clinical medicine, neutrophils, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Adrenal Cortex Hormones, Reference Values, gender, Pharmacology (medical), quantiferon-tb gold test, interferon gamma release assay, glucocorticoids, Latent tuberculosis, Incidence, Systemic Vasculitis, Age Factors, interferon, Middle Aged, Prognosis, 3. Good health, Exact test, Female, Vasculitis, Systemic vasculitis, Adult, medicine.medical_specialty, gamma release assay, immunosuppressive agents, Risk Assessment, QuantiFERON, Diagnosis, Differential, 03 medical and health sciences, Sex Factors, Rheumatology, Latent Tuberculosis, Predictive Value of Tests, Internal medicine, medicine, Humans, Retrospective Studies, Immunosuppression Therapy, 030203 arthritis & rheumatology, active tuberculosis, giant cell arteritis, Tuberculin Test, business.industry, Mycobacterium tuberculosis, Odds ratio, indeterminate results, medicine.disease, Giant cell arteritis, 030228 respiratory system, Case-Control Studies, Multivariate Analysis, business, Interferon-gamma Release Tests
Abstract

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.

Published
2019

3. Chronic use of Renin‐Angiotensin‐Aldosterone‐System blockers and mortality in COVID‐19: a multicenter prospective cohort and literature review

Author

Hikombo HITOTO, Anne Sophie Boureau, Cecile Tromeur, Benjamin Lefèvre, Paul Le Turnier, Manuel Etienne, Dominique Costagliola, Younes AIT TAMLIHAT, Alexandre Gaymard, Bernard CHOLLEY, Camille Couffignal, Sebastien Preau, JEAN-BAPTISTE ASSIE, Guillaume Louis, Manuel Rosa-calatrava, Kevin Bouiller, Olivier Terrier, Guillaume Martin-Blondel, Stella Rousset, Dominique Deplanque, Eric D'Ortenzio, Blandine Rammaert, Jean-Sébastien Hulot, Nicolas TERZI, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Unité de recherche clinique Paris Nord Val de Seine [Paris] (URC PNVS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Vulnérabilité cardiovasculaire, pathologie métabolique et endocrinienne (VCPME), Université des Antilles (UA), CHU de la Martinique [Fort de France], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Services de Maladies Infectieuses et Tropicales [CHU Bichat], Hôpital JeanMinjoz, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Anesthésie-Réanimation [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire [Grenoble] (CHU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Beziers (Service de Médecine Hospitalière), Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, PHRC20‐0424, Ministère des Affaires Sociales et de la Santé, French-Covid cohort investigators and study group, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
Male, medicine.medical_treatment, Angiotensin-Converting Enzyme Inhibitors, ClinicalTrials.gov/NCT04262921, 030226 pharmacology & pharmacy, law.invention, Cohort Studies, Renin-Angiotensin System, 0302 clinical medicine, Randomized controlled trial, law, Oxygen therapy, Pharmacology (medical), Prospective Studies, Prospective cohort study, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Hazard ratio, Middle Aged, 3. Good health, Cohort, Female, Original Article, angiotensin antagonists, France, medicine.medical_specialty, hypertension, RAAS blockers, 03 medical and health sciences, propensity score, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, COVID‐19, Diabetes mellitus, Internal medicine, medicine, Humans, Propensity Score, Pandemics, Aged, Pharmacology, business.industry, COVID-19, Original Articles, medicine.disease, mortality, Standardized mortality ratio, Propensity score matching, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Angiotensin II Type 1 Receptor Blockers, 030217 neurology & neurosurgery
Abstract

Aims The role of renin‐angiotensin‐aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID‐19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID‐19 and explored reasons for discrepancies in the literature. Methods and results We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID‐19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30‐day mortality for chronic users versus non‐users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8–1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86‐1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79–1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in‐hospital exposure measurement. Conclusion Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta‐analyses. RAAS blockers should not be discontinued during the pandemic, while in‐hospital management of these drugs will be clarified by randomized trials. NCT04262921.

Published
2021

4. Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study

Author

Hélène Guet-Revillet, Agnès Sommet, Stella Rousset, Guillaume Martin-Blondel, Peggy Gandia, Pierre Delobel, Caroline Protin, Jean Le Grusse, Laurent Sailler, Fatemeh Nourhashemi, Margaux Lafaurie, Hélène Derumeaux, Service des maladies infectieuses et tropicales [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire de pharmacologie médicale et clinique, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de Bactériologie-Hygiène [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Hôpital Joseph Ducuing, Laboratoire de Pharmacocinétique et de Toxicologie clinique [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital La Grave-Casselardit [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Tuberculosis, Antitubercular Agents, Logistic regression, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Older patients, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Risk factor, Aged, Retrospective Studies, business.industry, Odds ratio, Pyrazinamide, medicine.disease, 3. Good health, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract

International audience; Objectives: Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA.Methods: We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression.Results: Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5-9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified.Conclusion: In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs.

Published
2021

5. IL-7 immunotherapy for progressive multifocal leukoencephalopathy in a patient with already controlled HIV-1 infection on antiretroviral therapy

Author

Fabrice Bonneville, Stella Rousset, Guillaume Martin-Blondel, Pierre Delobel, Yassine Taoufik, Marie Guille, Catherine Mengelle, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, medicine.medical_specialty, medicine.medical_treatment, viruses, MESH: Leukoencephalopathy, Progressive Multifocal / diet therapy, Immunology, Treatment outcome, Human immunodeficiency virus (HIV), MESH: HIV Infections / complications, MESH: HIV Infections / drug therapy, medicine.disease_cause, MESH: Magnetic Resonance Imaging, Leukoencephalopathy, MESH: HIV-1 / isolation & purification, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Immunology and Allergy, MESH: Treatment Outcome, MESH: Anti-Retroviral Agents / administration & dosage, MESH: Humans, MESH: Middle Aged, medicine.diagnostic_test, MESH: Plasma / virology, business.industry, MESH: Interleukin-7 / administration & dosage, Progressive multifocal leukoencephalopathy, virus diseases, Magnetic resonance imaging, Immunotherapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Antiretroviral therapy, MESH: Immunotherapy / methods, MESH: Immunologic Factors / administration & dosage, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: JC Virus / isolation & purification, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Brain / diagnostic imaging, MESH: Brain / pathology, business, MESH: Viral Load, Viral load, MESH: Cerebrospinal Fluid / virology, MESH: Female
Abstract

International audience; The incidence of progressive multifocal leukoencephalopathy (PML) among patients living with HIV (PML-HIV) decreased in the antiretroviral therapy (ART) era. JC virus (JCV) infection of the brain remains a devastating disease. Given the lack of drugs controlling JCV, initiation of ART and subsequent recovery of JCV-specific CD4+ and CD8+ T-cell immune responses remain the only therapeutic option. Although the 1-year survival rate increased from 10% to 50%, other strategies are required.

Published
2019

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