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1. Epstein-Barr virus infection and clinical outcome in breast cancer patients correlate with immune cell TNF-α/IFN-γ response

Author: Catherine Fallecker, Samira Fafi-Kremer, Sofia Franco, Carlos Freire de Oliveira, Artur Paiva, Gina Marrão, Emmanuel Drouet, Mohammed Habib, Teresa Simões Silva, Patrice Morand, Dominique J. Bicout, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Instituto Português de Sangue e da Transplantação [Coimbra] (IPST), Laboratoire d'informatique Algorithmique : Fondements et Applications (LIAFA), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Networks, Graphs and Algorithms (GANG), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Instituto Superior de Engenharia de Coimbra, Universidade de Trás-os-Montes e Alto Douro (UTAD), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Patologia [Coimbra], Centro Hospitalar e Universitário [Coimbra], Departamento de Ginecologia [Coimbra], Universidade de Coimbra [Coimbra]-Centro Hospitalar e Universitário [Coimbra], Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Cancer Research, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Survival, T-Lymphocytes, Breast Neoplasms, Peripheral blood mononuclear cell, Virus, Interferon-gamma, Immune system, Breast cancer, Immunocompetent cells, EBV, Genetics, Medicine, Humans, Viral load, Epstein–Barr virus infection, IFN-γ, Survival analysis, Aged, Aged, 80 and over, Tumor, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Tumor Necrosis Factor-alpha, Middle Aged, medicine.disease, Survival Analysis, 3. Good health, Killer Cells, Natural, Oncology, Multivariate analysis, TNF-α, Immunology, biology.protein, Tumor necrosis factor alpha, Female, Antibody, business, Research Article, ZEBRA
Abstract: Background For nearly two decades now, various studies have reported detecting the Epstein-Barr virus (EBV) in breast cancer (BC) cases. Yet the results are unconvincing, and their interpretation has remained a matter of debate. We have now presented prospective data on the effect of EBV infection combined with survival in patients enrolled in a prospective study. Methods We assessed 85 BC patients over an 87-month follow-up period to determine whether EBV infection, evaluated by qPCR in both peripheral blood mononuclear cells (PBMCs) and tumor biopsies, interacted with host cell components that modulate the evolution parameters of BC. We also examined the EBV replicating form by the titration of serum anti-ZEBRA antibodies. Immunological studies were performed on a series of 35 patients randomly selected from the second half of the survey, involving IFN-γ and TNF-α intracellular immunostaining tests performed via flow cytometry analysis in peripheral NK and T cells, in parallel with EBV signature. The effect of the EBV load in the blood or tumor tissue on patient survival was analyzed using univariate and multivariate analyses, combined with an analysis of covariance. Results Our study represents the first ever report of the impact of EBV on the clinical outcome of BC patients, regardless of tumor histology or treatment regimen. No correlation was found between: (i) EBV detection in tumor or PBMCs and tumor characteristics; (ii) EBV and other prognostic factors. Notably, patients exhibiting anti-ZEBRA antibodies at high titers experienced poorer overall survival (p = 0.002). Those who recovered from their disease were found to have a measurable EBV DNA load, together with a high frequency of IFN-γ and TNF-α producing PBMCs (p = 0.04), which indicates the existence of a Th1-type polarized immune response in both the tumor and its surrounding tissue. Conclusions The replicative form of EBV, as investigated using anti-ZEBRA titers, correlated with poorer outcomes, whereas the latent form of the virus that was measured and quantified using the EBV tumor DNA conferred a survival advantage to BC patients, which could occur through the activation of non-specific anti-tumoral immune responses. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-665) contains supplementary material, which is available to authorized users.
Published: 2013

2. The Phenotypic Course of Age-Related Macular Degeneration for ARMS2/HTRA1: The EYE-RISK Consortium

Author: Thee, Eric, Colijn, Johanna, Cougnard-Grégoire, Audrey, Meester-Smoor, Magda, Verzijden, Timo, Hoyng, Carel, Fauser, Sascha, Hense, Hans-Werner, Silva, Rufino, Creuzot-Garcher, Catherine, Ueffing, Marius, Delcourt, Cécile, den Hollander, Anneke, Klaver, Caroline C.W., Epidemiology, Ophthalmology, Julien, Sabine, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Bordeaux Population Health Research Center, Inserm, Bordeaux, Radboud University Medical Center [Nijmegen], University Hospital of Cologne [Cologne], F. Hoffmann-La Roche A.G., Switzerland, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centro Hospitalar e Universitário [Coimbra], Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and University of Tübingen
Subjects: HTRA1, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Genotype, Age-related macular degeneration, Proteins, Retinal Drusen, High-Temperature Requirement A Serine Peptidase 1, Polymorphism, Single Nucleotide, Choroidal Neovascularization, Europe, Macular Degeneration, Phenotype, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Risk Factors, Complement Factor H, Humans, genetics, ARMS2, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose: Age-related maculopathy susceptibility 2 (ARMS2) is considered the most enigmatic of the genes for age-related macular degeneration (AMD). We investigated the phenotypic course and spectrum of AMD for the risk haplotype at the ARMS2 and high-temperature requirement A serine peptidase 1 (HTRA1) locus in a large European consortium. Design: Pooled analysis of 4 case-control and 6 cohort studies. Participants: Individuals (N = 17 204) aged 55 years or older participating in the European Eye Epidemiology consortium. Methods: Age-related macular degeneration features and macular thickness were determined on multimodal images; data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and were compared with a genetic risk score (GRS) of 19 variants at the complement pathway. Lifetime risks were estimated with Kaplan–Meier analyses in population-based cohorts. Main Outcome Measures: Age-related macular degeneration features and stage. Results: Of 2068 individuals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. For homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5–11.4), of choroidal neovascularization (CNV) was 11.2 (95% CI, 9.4–13.3), and of mixed late AMD was 12.2 (95% CI, 7.3–20.6). Cumulative lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. The latter received the diagnosis of late AMD 9.6 years (95% CI, 8.0–11.2) earlier than carriers of the nonrisk genotype. The risk haplotype was not associated with hard or soft drusen < 125 μm (OR, 1.2; 95% CI, 0.9–1.7), but risks increased significantly for soft drusen ≥ 125 μm (OR, 2.1; 95% CI, 1.5–3.0), up to an OR of 7.2 (95% CI, 3.8–13.8) for reticular pseudodrusen. Compared with persons with a high GRS for complement, homozygous carriers of ARMS2/HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2–5.4); risks of other characteristics were not different. Conclusions: Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a relatively early age. Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early signs are present. The phenotypic spectrum resembles that of complement genes, only with higher risks of CNV.
Published: 2022

3. 2020 EULAR points to consider for the prevention, screening, assessment and management of non-adherence to treatment in people with rheumatic and musculoskeletal diseases for use in clinical practice

Author: Bart J F van den Bemt, Michal Nudel, Fernando Estévez-López, Loreto Carmona, E. Moholt, Marieke Voshaar, Peter Böhm, Johannes W. J. Bijlsma, Tanja Stamm, Annamaria Iagnocco, Valentin Ritschl, Annette de Thurah, Andréa Marques, Laure Gossec, Daniel Aletaha, Razvan Dragoi, Emma Dures, Kirsten K. Viktil, Child and Adolescent Psychiatry / Psychology, Medizinische Universität Wien = Medical University of Vienna, University Medical Center [Utrecht], Deutsche Rheuma-Liga Bundesverband e.V, Victor Babeş University of Medicine and Pharmacy (UMFT), University of the West of England [Bristol] (UWE Bristol), Erasmus University Rotterdam, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Università degli studi di Torino = University of Turin (UNITO), Centro Hospitalar e Universitário [Coimbra], Dpt of Rheumatology [Oslo], Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, Radboud University Medical Center [Nijmegen], University of Oslo (UiO), University of Twente, Aarhus University Hospital, Instituto de Salud Musculoesqueletica (InMusc), Gestionnaire, Hal Sorbonne Université, and Psychology, Health & Technology
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, education, Online voting, General Biochemistry, Genetics and Molecular Biology, Occupational Therapists, Rheumatology, Rheumatic Diseases, Epidemiology, medicine, Humans, Immunology and Allergy, Musculoskeletal Diseases, Screening assessment, Task force, business.industry, epidemiology, health services research, patient care team, Health services research, Non adherence, n/a OA procedure, humanities, Europe, Physical Therapists, Clinical Practice, [SDV] Life Sciences [q-bio], Systematic review, Family medicine, business, Systematic Reviews as Topic
Abstract: Background Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. Objectives The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. Methods An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. Results Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients’ needs. The level of agreement ranged from 9.5 to 9.9 out of 10. Conclusions These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.
Published: 2021

4. Use of sodium glucose co-transporter 2 inhibitors in acute heart failure: a practical guidance

Author: João Pedro Ferreira, Joana Pimenta, Brenda Moura, Carlos Aguiar, Fátima Franco, 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), 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], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular R&D Centre-UnIC@RISE, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Department of Internal Medicine, Centro Hospitalar de Vila Nova de Gaia/Espinho, Hospital das Forcas Armadas [Porto, Portugal], Department of Cardiology, Chair of the Advanced Heart Failure and Heart Transplantation Unit, Santa Cruz Hospital, Centro Hospitalar de Lisboa Ocidental, Universidade de Coimbra [Coimbra], Centro Hospitalar e Universitário [Coimbra], Boehringer Ingelheim and Lilly Portugal provided financial support for journal fees only, and BOZEC, Erwan
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiology and Cardiovascular Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Aims: Heart failure (HF) is the most frequent cause of hospital admission among patients 65 years or older. Patients hospitalized for acutely decompensated chronic HF and 'de novo' acute heart failure (AHF) continue to experience unacceptably high post-discharge readmission and mortality rates.Methods and results: Until recently, trials had failed to improve outcome in patients with AHF irrespective of ejection fraction with exception of sodium-glucose co-transporter 2 inhibitors (SGLT2i) that improved clinical outcomes in patients hospitalized for AHF in the Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure (EMPULSE) and in the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trials.Conclusions: This document reviews the potential utility of SGLT2i in patients hospitalized for AHF.
Published: 2022

5. European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022

Author: Garbe, Claus, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lars, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacques, Höller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilios, Lebbé, Celeste, Lytvynenko, Bohdan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iris, Lorigan, Paul, European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital Schleswig-Holstein [Kiel, Germany], Charles University [Prague] (CU), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Odense University Hospital (OUH), King‘s College London, Université libre de Bruxelles (ULB), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University of L'Aquila [Italy] (UNIVAQ), University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Aix Marseille Université (AMU), Medizinische Universität Wien = Medical University of Vienna, Frankfurt University Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Aristotle University of Thessaloniki, Shupyk National Medical Academy of Postgraduate Education [Kiev] (SNMAPE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Clinic Barcelona Hospital Universitari, Hospital Universitario Virgen Macarena [Séville], Mount Vernon Cancer Centre [Northwood, UK] (MV2C), Mount Vernon Cancer Centre, University - Hospital of Modena and Reggio Emilia [Modena, Italy], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Athens Medical School [Athens], The University of Sydney, Centro Hospitalar e Universitário [Coimbra], Università degli studi di Trieste = University of Trieste, University of Manchester [Manchester], European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research and Treatment of Cancer (EORTC), Pecqueret, Valérie, Garbe, Clau, Amaral, Teresa, Peris, Ketty, Hauschild, Axel, Arenberger, Petr, Basset-Seguin, Nicole, Bastholt, Lar, Bataille, Veronique, Del Marmol, Veronique, Dréno, Brigitte, Fargnoli, Maria C, Forsea, Ana-Maria, Grob, Jean-Jacque, Höller, Christoph, Kaufmann, Roland, Kelleners-Smeets, Nicole, Lallas, Aimilio, Lebbé, Celeste, Lytvynenko, Bohdan, Malvehy, Josep, Moreno-Ramirez, David, Nathan, Paul, Pellacani, Giovanni, Saiag, Philippe, Stratigos, Alexander J, Van Akkooi, Alexander C J, Vieira, Ricardo, Zalaudek, Iri, and Lorigan, Paul
Subjects: Cancer Research, Sequential digital, Consensus, Skin Neoplasms, Follow-up examinations, [SDV]Life Sciences [q-bio], Consensu, Mutation testing, NEEDLE-ASPIRATION-CYTOLOGY, Primary diagnosis, MALIGNANT-MELANOMA, AJCC classification, Positron Emission Tomography Computed Tomography, Dermatoscopy, Humans, MELANOCYTIC NEVI, Follow-up examination, Imaging diagnostic, Melanoma, SENTINEL-NODE BIOPSY, ComputingMilieux_MISCELLANEOUS, Primary diagnosi, AMERICAN JOINT COMMITTEE, Neoplasm Staging, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Confocal reflectance microscopy, Cutaneous melanoma, Imaging diagnostics, Sequential digital dermatoscopy, Total body photography, Neoplasm Recurrence, Local, [SDV] Life Sciences [q-bio], ACRAL LENTIGINOUS MELANOMA, Neoplasm Recurrence, Oncology, Local, TOTAL-BODY PHOTOGRAPHY, REFLECTANCE CONFOCAL MICROSCOPY, Settore MED/35 - MALATTIE CUTANEE E VENEREE, FOLLOW-UP, Human
Abstract: International audience; Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.
Published: 2022

6. COVID-19 pandemic

Author: W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: 0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.
Published: 2021

7. Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries

Author: Michael Blauth, John A. Kanis, Reto W. Kressig, José António Pereira da Silva, Endel J. Orav, Angélique Sadlon, Michael Gagesch, Simeon Schietzel, Andreas Egli, Bruno Vellas, Patricia O. Chocano-Bedoya, Walter C. Willett, Heike A. Bischoff-Ferrari, René Rizzoli, Universität Zürich [Zürich] = University of Zurich (UZH), University of Bern, University of Fribourg, Harvard T.H. Chan School of Public Health, University of Basel (Unibas), Institut du Vieillissement, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Geneva University Hospitals and Geneva University, Centro Hospitalar e Universitário [Coimbra], University of Coimbra [Portugal] (UC), Leopold Franzens Universität Innsbruck - University of Innsbruck, University of Sheffield [Sheffield], University hospital of Zurich [Zurich], Malbec, Odile, University of Zurich, and Schietzel, Simeon
Subjects: Gerontology, Male, 11221 Department of Aging Medicine, [SDV]Life Sciences [q-bio], 2717 Geriatrics and Gerontology, 610 Medicine & health, Healthy Aging, 360 Social problems & social services, Prevalence, Medicine, Humans, Healthy aging, Aged, Hand Strength, business.industry, Senior, DO-HEALTH, [SDV] Life Sciences [q-bio], Older, Cross-Sectional Studies, Female, Independent Living, Geriatrics and Gerontology, business
Abstract: Background To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. Methods Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 Results Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p Conclusions Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. Trial registration DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry (clinicaltrials.gov), and under the protocol number 2012–001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).
Published: 2022

8. Correspondence on 'Re-examining Remission Definitions in Rheumatoid Arthritis: Considering the \textsc28-\textscJoint Disease Activity Score, C-reactive Protein Level and Patient Global Assessment' by Felson et Al

Author: Ricardo J. O. Ferreira, Paco M. J. Welsing, Johannes W. G. Jacobs, Laure Gossec, Mwidimi Ndosi, Pedro M. Machado, Désirée van der Heijde, José A. P. da Silva, Centro Hospitalar e Universitário [Coimbra], University Medical Center [Utrecht], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of the West of England [Bristol] (UWE Bristol), University College of London [London] (UCL), Leiden University Medical Center (LUMC), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV] Life Sciences [q-bio], Rheumatology, [SDV]Life Sciences [q-bio]
Abstract: International audience; No abstract available
Published: 2022

9. Reexamining Remission Definitions in Rheumatoid Arthritis: Considering the 28-joint Disease Activity Score, C-reactive Protein Level, and Patient Global Assessment: Comment on the Article by Felson et Al

Author: Ricardo J. O. Ferreira, Paco M. J. Welsing, Johannes W. G. Jacobs, Laure Gossec, Mwidimi Ndosi, Pedro M. Machado, Désirée Heijde, José A. P. Silva, Centro Hospitalar e Universitário [Coimbra], University Medical Center [Utrecht], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of the West of England [Bristol] (UWE Bristol), University College of London [London] (UCL), Leiden University Medical Center (LUMC), and Gestionnaire, Hal Sorbonne Université
Subjects: Arthritis, Rheumatoid, [SDV] Life Sciences [q-bio], C-Reactive Protein, Rheumatology, Antirheumatic Agents, [SDV]Life Sciences [q-bio], Humans
Abstract: International audience
Published: 2022

10. Correspondence on 'Re-examining Remission Definitions in Rheumatoid Arthritis: Considering the 28-Joint Disease Activity Score, C Reactive Protein Level and Patient Global Assessment' by Felson et Al

Author: Ricardo J O Ferreira, Paco M J Welsing, Johannes WG Jacobs, Laure Gossec, Mwidimi Ndosi, Pedro M Machado, Désirée van der Heijde, Jose AP Da Silva, Gestionnaire, Hal Sorbonne Université, Centro Hospitalar e Universitário [Coimbra], Health Sciences Research Unit: Nursing [Coimbra, Portugal] (UICiSA:E), Escola Superior de Enfermagem de Coimbra [Coimbra, Portugal], University Medical Center [Utrecht], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of the West of England [Bristol] (UWE Bristol), University College of London [London] (UCL), and Leiden University Medical Center (LUMC)
Subjects: [SDV] Life Sciences [q-bio], Rheumatology, arthritis, rheumatoid, patient reported outcome measures, inflammation, [SDV]Life Sciences [q-bio], Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract: International audience
Published: 2022

11. Recommendations for the execution and reporting of skin ultrasound in systemic sclerosis: an international collaboration under the WSF skin ultrasound group

Author: Tânia Santiago, Eduardo José Ferreira Santos, Barbara Ruaro, Gemma Lepri, Lorraine Green, Marie Wildt, Shinji Watanabe, Alain Lescoat, Roger Hesselstrand, Francesco del Galdo, John D Pauling, Lucy Jean Reeve, Maria Antonieta D'Agostino, Marco Matucci-Cerinic, Annamaria Iagnocco, Jose Antonio Pereira da Silva, Centro Hospitalar e Universitário [Coimbra], University of Coimbra [Portugal] (UC), Health Sciences Research Unit: Nursing [Coimbra, Portugal] (UICiSA:E), Escola Superior de Enfermagem de Coimbra [Coimbra, Portugal], Università degli studi di Trieste = University of Trieste, Università degli Studi di Firenze = University of Florence (UniFI), Leeds Institute of Molecular Medicine, University of Leeds, Lund University [Lund], Nippon Medical School [Tokyo, Japon], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], NIHR - Leeds Musculoskeletal Biomedical Research Unit (LMBRU), National Institute for Health Research (NIHR), Royal United Hospitals Bath (RUH), University of Bath [Bath], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Università degli studi di Torino = University of Turin (UNITO), Santiago, Tânia, Santos, Eduardo José Ferreira, Ruaro, Barbara, Lepri, Gemma, Green, Lorraine, Wildt, Marie, Watanabe, Shinji, Lescoat, Alain, Hesselstrand, Roger, Del Galdo, Francesco, Pauling, John D, Reeve, Lucy Jean, D'Agostino, Maria Antonieta, Matucci-Cerinic, Marco, Iagnocco, Annamaria, and da Silva, Jose Antonio Pereira
Subjects: Scleroderma, Systemic, Outcome and Process Assessment, Health Care, Ultrasonography, Consensus, Humans, Reproducibility of Results, Skin, Rheumatology, [SDV]Life Sciences [q-bio], Immunology, Systemic, Reproducibility of Result, Consensu, Outcome and Process Assessment, Scleroderma, Health Care, Immunology and Allergy, Human
Abstract: ObjectiveUltrasound is a promising tool to foster much-needed improvement of skin assessment in systemic sclerosis (SSc). Our aim was to develop evidence and expert opinion-based recommendations to promote the standardisation and harmonisation of technical execution and reporting of skin ultrasound studies in SSc.MethodsA multidisciplinary task force of 16 members from five European countries and Japan was convened under the auspices of World Scleroderma Foundation. First, a systematic literature review (SLR) was performed. Then, each member proposed and formulated items to the overarching principles, recommendations and research agenda. Two rounds of mails exchange for consensus as well as an on-line meeting were performed to debate and refine the proposals. Two Delphi rounds of voting resulted in the final recommendations. Levels of evidence and strengths of recommendations were assigned, and task force members voted anonymously on the level of agreement with each of the items.ResultsFive overarching principles and seven recommendations were developed, based on an SLR and expert opinion, through consensus procedures. The overarching principles highlight the promising role of skin ultrasound in SSc assessment, the need for standardisation of technical aspects, sufficient training and adequate equipment. The recommendations provide standards for the execution and reporting of skin ultrasound in SSc. The research agenda includes the need for more research into unmet needs according to Outcome Measures in Rheumatology Algorithm requirements.ConclusionThese are the first recommendations providing guidance on the execution and reporting of skin ultrasound in SSc patients, aiming at improving the interpretability, reliability and generalisability of skin ultrasound, thus consolidating its role in research and practice.
Published: 2022

12. Safety of Vaccination against SARS-CoV-2 in People with Rheumatic and Musculoskeletal Diseases: Results from the EULAR Coronavirus Vaccine (COVAX) Physician-Reported Registry

Author: Pedro M Machado, Saskia Lawson-Tovey, Anja Strangfeld, Elsa F Mateus, Kimme L Hyrich, Laure Gossec, Loreto Carmona, Ana Rodrigues, Bernd Raffeiner, Catia Duarte, Eric Hachulla, Eric Veillard, Eva Strakova, Gerd R Burmester, Gözde Kübra Yardımcı, Jose A Gomez-Puerta, Julija Zepa, Lianne Kearsley-Fleet, Ludovic Trefond, Maria Cunha, Marta Mosca, Martina Cornalba, Martin Soubrier, Nicolas Roux, Olivier Brocq, Patrick Durez, Richard Conway, Tiphaine Goulenok, Johannes WJ Bijlsma, Iain B McInnes, Xavier Mariette, University College London Hospitals (UCLH), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Centre for Genetics and Genomics Versus Arthritis, Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Instituto de Salud Musculoesqueletica (InMusc), Central Hospital of Bolzano, Centro Hospitalar e Universitário [Coimbra], CHU Lille, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, University of Pisa - Università di Pisa, CHU Clermont-Ferrand, Hôpital Princesse Grace [Monaco], Cliniques Universitaires Saint-Luc [Bruxelles], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Medical Center [Utrecht], Hôpital Bicêtre, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: Male, COVID-19 Vaccines, antirheumatic agents, Epidemiology, [SDV]Life Sciences [q-bio], Immunology, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Muscular Diseases, Rheumatic Diseases, Immunology and Allergy, Humans, autoimmune diseases, Musculoskeletal Diseases, Registries, skin and connective tissue diseases, Aged, SARS-CoV-2, Vaccination, COVID-19, Middle Aged, Female, epidemiology, Rheumatologists, Immunosuppressive Agents
Abstract: ObjectivesTo describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD).MethodsPhysician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively.ResultsThe study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD).ConclusionThe safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.
Published: 2022

13. The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Author: Roberts, Jason, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, de Waele, Jan, Deans, Renae, Eastwood, Glenn, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios, Lassig-Smith, Melissa, Laterre, Pierre-Francois, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne, Rello, Jordi, Roberts, Darren, Roberts, Michael, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi, Paul, Sanjoy, Lipman, Jeffrey, Andresen, Max, Baltazar, Sónia, Barbar, Saber, Costa, Eulália, Durand, Dominique, Freitas, Ricardo, Frey, Otto, Guerra Valero, Yarmarly, Haughton, Margaret, Koeberer, Andreas, Kollef, Marin, Klein, Kerenaftali, Mehta, Ravindra, Mckenzie, Cathy, Muller, Laurent, Nair, Priya, Nayyar, Vineet, Ordóñez Mejia, Jenny, Panagou, Georgia-Laura, Paxton, Jody, Peck, Leah, Samanta, Mayukh, Vincent, Jean-Louise, Wan, Ruth, Young, Helen, University of Southern Queensland (USQ), Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Princess Alexandra Hospital, Brisbane, SMARRT Study, ANZICS Clinical Trials Group, The Chinese University of Hong Kong [Hong Kong], Austin Hospital [Melbourne], Austin Health, The Ottawa Hospital, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Westmead Hospital [Sydney], The University of Sydney, The Queen Elizabeth Hospital (TQEH), University of Adelaide, Monash University [Melbourne], Royal Darwin Hospital, Flinders University [Adelaide, Australia], National Critical Care and Trauma Response Centre (Darwin) (NCCTRC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Corporació Sanitària Parc Taulí, Barcelona Biomedical Research Park (PRBB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, QIMR Berghofer Medical Research Institute, Centro Hospitalar e Universitário [Coimbra], Athens Naval Hospital, University of Queensland [Brisbane], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Kliniken Landkreis Heidenheim, Melbourne EpiCentre, The Royal Melbourne Hospital, Hospital Clínic de Barcelona (ICMiD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Nepean Hospital, Ghent University Hospital, Universidad de Santiago de Chile [Santiago] (USACH), University of Sydney and Nepean Hospital, Hospital Tengku Ampuan Afzan (HTAA), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital of Ioannina, Royal Brisbane & Women's Hospital, Cliniques universitaires St Luc [Bruxelles], Guy's and St Thomas' Hospital [London], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universitat Internacional de Catalunya [Barcelona] (UIC), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, International Islamic University Malaysia [Kuala Lumpur], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of South Australia [Adelaide], Basil Hetzel Institute (BHI), Translational Research Institute (TRI), Gold Coast University Hospital, University Hospital of Tarragona 'Joan XXIII', University Rovirai Virgili de Tarragona (URV), Ochsner Medical Center, The Queen Elizabeth Hospital, Hospital Clínic de Barcelona, Roberts, Jason A., Joynt, Gavin M., Lee, Anna, Choi, Gordon, Roberts, Michael S., Sinnollareddy, Mahipal, and Lipman, Jeffrey
Subjects: 0301 basic medicine, Continuous renal replacement therapy, medicine.medical_treatment, continuous renal replacement therapy, Antibiotics, urologic and male genital diseases, MESH: Meropenem, 030226 pharmacology & pharmacy, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Prospective Studies, pharmacokinetic, extended daily dialysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Extended daily dialysis, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Renal Replacement Therapy, Infectious Diseases, MESH: Critical Illness, Vancomycin, beta-lactam, medicine.drug, MESH: Piperacillin, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Critical Illness, Beta-lactam, 030106 microbiology, Pharmacokinetic, Meropenem, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Internal medicine, Intensive care, medicine, Humans, Trough Concentration, Dosing, Renal replacement therapy, Piperacillin, MESH: Humans, business.industry, MESH: Prospective Studies, renal clearance, MESH: Renal Replacement Therapy, business, Renal clearance
Abstract: Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
Published: 2020

14. SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study

Author: José María Alvaro Gracía, Bruno Fautrel, Mathieu Vautier, David Saadoun, José António Pereira da Silva, Patrice Cacoub, Alessandra Bortoluzzi, Henry Penn, Nikita Khmelinskii, Juan Carlos Nieto Gonzalez, Laure Gossec, Shahir Hamdulay, Isabel Castrejón, Carlo Alberto Scirè, Marlene Sousa, I. Andreica, Mariana Luís, Ettore Silvagni, Xenofon Baraliakos, Matheus Vieira, Pedro Machado, Matthieu Resche-Rigon, Saadoun, D, Vieira, M, Vautier, M, Baraliakos, X, Andreica, I, da Silva, J, Sousa, M, Luis, M, Khmelinskii, N, Gracia, J, Castrejon, I, Gonzalez, J, Scire, C, Silvagni, E, Bortoluzzi, A, Penn, H, Hamdulay, S, Machado, P, Fautrel, B, Cacoub, P, Resche-Rigon, M, Gossec, L, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CHU Tenon] (CeréMAIA), CHU Tenon [AP-HP], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Ruhr University Bochum (RUB), Centro Hospitalar e Universitário [Coimbra], Universidade de Coimbra [Coimbra], Universidade de Lisboa, Hospital General Universitario 'Gregorio Marañón' [Madrid], Università degli Studi di Ferrara = University of Ferrara (UniFE), London North West University Healthcare NHS Trust (LNWH), University College of London [London] (UCL), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Gestionnaire, Hal Sorbonne Université, and Repositório da Universidade de Lisboa
Subjects: medicine.medical_specialty, Cross-sectional study, business.industry, [SDV]Life Sciences [q-bio], Incidence (epidemiology), Immunology, Outbreak, Articles, Disease, Odds ratio, medicine.disease, NO, [SDV] Life Sciences [q-bio], Rheumatology, Internal medicine, Epidemiology, medicine, Immunology and Allergy, Seroprevalence, Immune-mediated inflammatory diseases, business, rheumatic disease, COVID
Abstract: © 2021 Elsevier Ltd. All rights reserved, Background: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID-19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management. Methods: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjögren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237. Findings: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73·9%] women and 789 [26·1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5·5% [95% CI 4·7-6·4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4·0% [95% CI 3·4-4·8]) of 3028 patients, of whom 24 (19·7%) were admitted to hospital and four (3·3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1·18, 95% CI 1·05-1·33; p=0·0063), and higher numbers of recent disease flares (1·27, 1·02-1·58; p=0·030), whereas use of biological therapy was associated with reduced risk (0·51, 0·32-0·82; p=0·0057). At least one disease flare occurred in 654 (21·6%) of 3028 patients. Over the study period, 519 (20·6%) of 2514 patients had treatment changes, of which 125 (24·1%) were due to the pandemic. Interpretation: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic., Pfizer, Sanofi, Amgen, Galapagos, and Lilly funded this study through unrestricted grants.
Published: 2021

15. EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis

Author: Elsa F Mateus, Dorcas E. Beaton, Alessia Alunno, Mary Lucy Marques, Polina Putrik, Fernando Manuel Pimentel dos Santos, Karen Walker-Bone, Suzanne M M Verstappen, Boryana Boteva, Márta Péntek, J L Severens, Neil Betteridge, Marieke M. ter Wee, Francis Guillemin, Sofia Ramiro, Mathilda Björk, Lydia Abasolo, Elena Nikiphorou, Bruno Fautrel, Rene Westhovens, Maarten Boers, Johan K. Wallman, Annelies Boonen, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Leiden University Medical Center (LUMC), Centro Hospitalar e Universitário [Coimbra], Università degli Studi di Perugia (UNIPG), Hospital Clínico Universitario San Carlos, St. Michael's Hospital, Neil Betteridge Associates, London, Linköping University (LIU), Vrije Universiteit Brussel (VUB), European League Against Rheumatism (EULAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), 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), King‘s College London, Óbuda University [Budapest], Centro Hospitalar de Lisboa Central E.P.E, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Manchester [Manchester], Southampton General Hospital, Lund University [Lund], Skane University Hospital [Lund], Vrije Universiteit Amsterdam [Amsterdam] (VU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidemiology and Data Science, Rheumatology, AII - Inflammatory diseases, APH - Methodology, APH - Societal Participation & Health, Erasmus School of Health Policy & Management, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, Interne Geneeskunde, MUMC+: MA Reumatologie (9), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Gestionnaire, Hal Sorbonne Université, Università degli Studi di Perugia = University of Perugia (UNIPG), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and 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)
Subjects: Data Analysis, Research Report, Work, endocrine system diseases, [SDV]Life Sciences [q-bio], GUIDELINES, Outcome (game theory), 0302 clinical medicine, Multidisciplinary approach, Outcome Assessment, Health Care, Health care, Immunology and Allergy, Medicine, 030212 general & internal medicine, Duration (project management), Societies, Medical, PRODUCTIVITY, ANKYLOSING-SPONDYLITIS, spondylitis, health care, [SDV] Life Sciences [q-bio], Europe, ankylosing, Work (electrical), arthritis, Research Design, Professional association, Employment, medicine.medical_specialty, rheumatoid, Advisory Committees, Immunology, Guidelines as Topic, General Biochemistry, Genetics and Molecular Biology, Domain (software engineering), 03 medical and health sciences, utcome and process assessment, Rheumatology, SDG 3 - Good Health and Well-being, Humans, In patient, VALIDITY, Rheumatology and Autoimmunity, 030203 arthritis & rheumatology, Reumatologi och inflammation, business.industry, Recommendation, Work Engagement, outcome and process assessment, RHEUMATOID-ARTHRITIS, Family medicine, ACTIVITY IMPAIRMENT QUESTIONNAIRE, psoriatic, business, CONTEXTUAL FACTORS
Abstract: BackgroundClinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.ObjectivesTo develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.MethodsThe EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.ResultsTwo overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1–3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5–7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).ConclusionAdherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.
Published: 2021

16. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA

Author: Jere Reijula, De Yun Wang, Ralph Mösges, Tomohisa Iinuma, Jean Luc Fauquert, Nelson Rosario, Yehia El-Gamal, René Maximiliano Gómez, Tari Haahtela, Vincenzo Patella, Lorenzo Cecchi, Petr Panzner, Yoshitaka Okamoto, Oliver Pfaar, Luis Caraballo, Paulo Augusto Moreira Camargos, Filip Raciborski, Florin Mihaltan, Ken Ohta, Brian J. Lipworth, Kimi Okubo, Juan Carlos Ivancevich, Fulvio Braido, Ioana Agache, Frederico S. Regateiro, Neven Miculinic, Tuula Vasankari, R. Emuzyte, Arunas Valiulis, Yousser Mohammad, Torsten Zuberbier, Osman M. Yusuf, Ewa Jassem, Cezmi A. Akdis, Jean Bousquet, Alessandro Fiocchi, Jan Hagemann, Claus Bachert, Davor Plavec, K. S. Bennoor, Marek Jutel, Désirée Larenas-Linnemann, Stephen Montefort, Stefano Del Giacco, Przemyslaw Kardas, Erkka Valovirta, Mark S. Dykewicz, Antonio Valero, Wienczyslawa Czarlewski, Thomas B. Casale, Gabrielle L. Onorato, Omer Kalayci, Ludger Klimek, Joaquin Sastre, João Fonseca, Siân Williams, Karl Christian Bergmann, Marek Niedoszytko, Bilun Gemicioglu, Mario E. Zernotti, Musa Khaitov, H. Neffen, Robert M. Naclerio, Joaquim Mullol, Ana Pereira, Piotr Kuna, Michael Makris, Maria Teresa Ventura, Ioanna Tsiligianni, Dirceu Solé, Arzu Yorgancioglu, Charlotte Suppli-Ulrik, M. Gotua, Emmanuel P. Prokopakis, Dana Wallace, Jorge Maspero, Wytske Fokkens, Eckard Hamelmann, Antonino Romano, Dejan Dokic, Todor A. Popov, Violeta Kvedariene, Derek K. Chu, Anna Bedbrook, Dermot Ryan, Motohiro Ebisawa, Tomas Chivato, Giovanni Passalacqua, Menachem Rottem, Mário Morais-Almeida, Victoria Cardona, Bolesław Samoliński, Cristiana Stellato, Nikolaos G. Papadopoulos, Milan Sova, Jaime Correia-de-Sousa, Sietze Reitsma, Cemal Cingi, Francesca Puggioni, Robyn E O'Hehir, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Internal Medicine and Rehabilitation, Department of Public Health, Clinicum, Keuhkosairauksien yksikkö, Helsinki University Hospital Area, University of Helsinki, University Medical Center of the Johannes Gutenberg-University Mainz, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Wrocław [Poland] (UWr), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Transilvania University of Brasov, Humboldt University Of Berlin, Medical Consulting Czarlewski, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), MASK-air, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], National Institute of Diseases of the Chest and Hospital (NIDCH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ospedale Policlinico San Martino [Genoa], Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cartagena, Foundation for the Development of Medical and Biological Sciences (FUNDEMEB), Vall d'Hebron University Hospital [Barcelona], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], CEU-San Pablo University and HM-Hospitals School of Medicine, McMaster University [Hamilton, Ontario], Eskisehir Osmangazi University, Universidade do Minho = University of Minho [Braga], Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], The International Primary Care Respiratory Group (IPCRG), Università degli Studi di Cagliari = University of Cagliari (UniCa), Sts. Cyril and Methodius University, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital [Kanagawa, Japan], Ain Shams University (ASU), Vilnius University [Vilnius], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bambino Gesù Children’s Hospital [Rome, Italy], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, CUF Porto Hospital, Cerrahpasa Faculty of Medicine, Istanbul University, ALAS Medical Institute, Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bielefeld = Bielefeld University, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Medical University of Gdańsk, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Medical University of Łódź (MUL), Federal Medicobiological Agency [Moscow, Russian Federation], Hospital Medica Sur [Mexico City, Mexico], Ninewells Hospital and Medical School [Dundee], University General Hospital ' Attikon ' [Athens, Greece], Argentine Association of Allergy and Immunology, Marius Nasta Institute of Pneumology, Tishreen University, Université de Damas = Damascus University, University of Malta [Malta], Hospital CUF Descobertas, Clinical Research International Ltd [Hamburg, Germany] (CRI), Johns Hopkins University School of Medicine [Baltimore], Nemours/Alfred I. du Pont Hospital for Children, Monash University [Melbourne], Tokyo National Hospital, Nippon Medical School [Tokyo, Japon], Medicine Charles University and General Faculty Hospital in Prague, Royal Manchester Children's Hospital, University of Manchester [Manchester], Università degli studi di Genova = University of Genoa (UniGe), 'Santa Maria della Speranza' Hospital, Philipps Universität Marburg = Philipps University of Marburg, J.J. Strossmayer University of Osijek, Children’s Hospital Srebrnjak [Zagreb, Croatia], St. Ivan Rilski University Hospital, University of Crete [Heraklion] (UOC), IRCCS Humanitas [Rozzano, Italy], Medical University of Warsaw - Poland, Centro Hospitalar e Universitário [Coimbra], Amsterdam UMC - Amsterdam University Medical Center, Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Clinica G.B. Morgagni (Fondazione Mediterranea), Pontifical Catholic University of Paraná (PUCPR), Pontifícia Universidade Católica do Paraná (PUCPR), Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Federal University of Sao Paulo (Unifesp), University Hospital Olomouc [Czech Republic], University of Salerno (UNISA), Copenhagen University Hospital, Universitat de Barcelona (UB), European Academy of Paediatrics (EAP/UEMS-SP), University of Turku, Suomen Terveystalo Allergy Clinic, Finnish Lung Health Association, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Nova Southeastern University (NSU), Yong Loo Lin School of Medicine [Singapore], Department of Biology, Faculty of Sciences & Liberal Arts, Celal Bayar University, Manisa Celal Bayar University, The Allergy & Asthma Institute, Pakistan (IPCRG), Universidad Nacional de Villa María, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Allergiezentrum Wiesbaden, Salvy-Córdoba, Nathalie, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: 0301 basic medicine, Allergy, MESH: Asthma, Common Cold, allergic rhinitis, common cold, cough, COVID-19, smell, Consensus, Humans, SARS-CoV-2, Asthma, Rhinitis, Allergic, Disease, Care, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: COVID-19, Rhinitis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Common cold, 3. Good health, MESH: Rhinitis, Allergic, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Immunology, Signs and symptoms, Asymptomatic, 03 medical and health sciences, Allergic, COVID‐19, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Consensus, MESH: Humans, business.industry, Rhinitis, Sinusitis, and Upper Airway Disease, CARE, medicine.disease, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ORIGINAL ARTICLES, Airway, business, MESH: Common Cold
Abstract: Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
Published: 2021

17. Prevention, screening, assessing and managing of non-adherent behaviour in people with rheumatic and musculoskeletal diseases:systematic reviews informing the 2020 EULAR points to consider

Author: Fernando Estévez-López, Peter Böhm, Andréa Marques, Emma Dures, J. Bijlsma, Tanja Stamm, Marieke Voshaar, Bart J F van den Bemt, Laure Gossec, Kirsten K. Viktil, E. Moholt, Michal Nudel, Annamaria Iagnocco, Loreto Carmona, Daniel Aletaha, José B Negrón, Razvan Dragoi, Valentin Ritschl, Annette de Thurah, Conni Skrubbeltrang, Child and Adolescent Psychiatry / Psychology, Psychology, Health & Technology, Medizinische Universität Wien = Medical University of Vienna, Utrecht University [Utrecht], Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, West University of Timișoara [Roumanie] (WUT), University of the West of England [Bristol] (UWE Bristol), Erasmus University Rotterdam, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Torino (UNITO), Universidad de Puerto Rico - UPR (PUERTO RICO), University of Puerto Rico (UPR), University of Haifa [Haifa], Centro Hospitalar e Universitário [Coimbra], Dpt of Rheumatology [Oslo], Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, Aalborg University [Denmark] (AAU), Nijmegen Medical Centre [Nijmegen], Oslo University Hospital [Oslo], University of Twente [Netherlands], Instituto de Salud Musculoesqueletica (InMusc), Aarhus University Hospital, Gestionnaire, HAL Sorbonne Université 5, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Torino = University of Turin (UNITO), and University of Twente
Subjects: medicine.medical_specialty, Epidemiology, media_common.quotation_subject, Immunology, Psychological intervention, lcsh:Medicine, Health services research, Patient Care Team, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Rheumatology, medicine, Immunology and Allergy, Humans, Quality (business), 030212 general & internal medicine, Musculoskeletal Diseases, Exercise, media_common, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Gold standard, lcsh:R, Evidence-based medicine, 3. Good health, Systematic review, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Family medicine, Patient Compliance, business, Delivery of Health Care, Patient education, Systematic Reviews as Topic
Abstract: ObjectiveTo analyse how non-adherence to prescribed treatments might be prevented, screened, assessed and managed in people with rheumatic and musculoskeletal diseases (RMDs).MethodsAn overview of systematic reviews (SR) was performed in four bibliographic databases. Research questions focused on: (1) effective interventions or strategies, (2) associated factors, (3) impact of shared decision making and effective communication, (4) practical things to prevent non-adherence, (5) effect of non-adherence on outcome, (6) screening and assessment tools and (7) responsible healthcare providers. The methodological quality of the reviews was assessed using AMSTAR-2. The qualitative synthesis focused on results and on the level of evidence attained from the studies included in the reviews.ResultsAfter reviewing 9908 titles, the overview included 38 SR on medication, 29 on non-pharmacological interventions and 28 on assessment. Content and quality of the included SR was very heterogeneous. The number of factors that may influence adherence exceed 700. Among 53 intervention studies, 54.7% showed a small statistically significant effect on adherence, and all three multicomponent interventions, including different modes of patient education and delivered by a variety of healthcare providers, showed a positive result in adherence to medication. No single assessment provided a comprehensive measure of adherence to either medication or exercise.ConclusionsThe results underscore the complexity of non-adherence, its changing pattern and dependence on multi-level factors, the need to involve all stakeholders in all steps, the absence of a gold standard for screening and the requirement of multi-component interventions to manage it.
Published: 2020

18. The role of rare compound heterozygous events in autism spectrum disorder

Author: Thomas Bourgeron, Alistair T. Pagnamenta, Jeremy R. Parr, Louise Gallagher, Christine M. Freitag, Jacob A. S. Vorstman, Sean Ennis, Isaac J. Nijman, Fabrice Colas, Kristel R. van Eijk, Bochao Danae Lin, Jurjen J. Luykx, Jelena Medic, Sabine M. Klauck, Elena Maestrini, Astrid M. Vicente, Richard Anney, Guiomar Oliveira, Elena Bacchelli, Hilary Coon, Andreas G. Chiocchetti, William J. Brands, Utrecht University [Utrecht], Henan University, Kaifeng, Newcastle University [Newcastle], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Goethe-Universität Frankfurt am Main, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of Utah School of Medicine [Salt Lake City], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Centro Hospitalar e Universitário [Coimbra], University of Oxford [Oxford], Trinity College Dublin, University College Dublin [Dublin] (UCD), Cardiff University, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), GGNet Mental Health [Apeldoorn, The Netherlands], The Hospital for sick children [Toronto] (SickKids), University of Toronto, This study has been funded by the Dutch Brain Foundation (Hersenstichting Nederland) to JV., Lin B.D., Colas F., Nijman I.J., Medic J., Brands W., Parr J.R., van Eijk K.R., Klauck S.M., Chiocchetti A.G., Freitag C.M., Maestrini E., Bacchelli E., Coon H., Vicente A., Oliveira G., Pagnamenta A.T., Gallagher L., Ennis S., Anney R., Bourgeron T., Luykx J.J., Vorstman J., Henan University, University of Oxford, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Proband, DNA Copy Number Variations, Autism Spectrum Disorder, Autism, Biology, Compound heterozygosity, ASD, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Gene, Biological Psychiatry, Alleles, MESH: Autism Spectrum Disorder, Genetics, Comparative genomics, MESH: Humans, MESH: Alleles, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Genetic Predisposition to Disease, Autism spectrum disorders, medicine.disease, Penetrance, Autism Spectrum Disorders, Autism, CNVs, Deletions, SNVs, Compound Heterozygosity, Targeted Sequencing, Psychiatry and Mental health, 030104 developmental biology, Autism spectrum disorder, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: DNA Copy Number Variations, 030217 neurology & neurosurgery
Abstract: The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X2 = 6.69, p = 0.0097). After filtering for those variants predicted to be most deleterious, we observed 21 of such variants in probands versus 8 in their deletion-transmitting parents (X2 = 5.82, p = 0.016). Finally, cumulative CADD scores conferred by these variants were significantly higher in probands than in deletion-transmitting parents (burden test, β = 0.13; p = 1.0 × 10−5). Our findings suggest that the compound heterozygosity described in the current study may be one of several mechanisms explaining variable penetrance of CNVs with known pathogenicity for ASD.
Published: 2020

19. Dual target strategy : a proposal to mitigate the risk of overtreatment and enhance patient satisfaction in rheumatoid arthritis

Author: José António Pereira da Silva, Ricardo J O Ferreira, Désirée van der Heijde, Pedro Machado, Eduardo Santos, Johannes W G Jacobs, Laure Gossec, Maarten de Wit, Cátia Duarte, Mwidimi Ndosi, Gestionnaire, Hal Sorbonne Université, Centro Hospitalar e Universitário [Coimbra], University of the West of England [Bristol] (UWE Bristol), University Hospitals Bristol, VU University Medical Center [Amsterdam], Public Health Service of Amsterdam, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Universidade de Coimbra [Coimbra], University Medical Center [Utrecht], University College of London [London] (UCL), Leiden University Medical Center (LUMC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidade do Porto, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, rheumatoid arthritis, medicine.medical_specialty, Letter, Immunology, MEDLINE, Arthritis, Medical Overuse, Disease, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Rheumatology, Internal medicine, Humans, Medicine, Immunology and Allergy, Overdiagnosis, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, treatment, Biochemistry, Genetics and Molecular Biology(all), business.industry, medicine.disease, patient perspective, 3. Good health, Antirheumatic Agents, 030104 developmental biology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Patient Satisfaction, inflammation, Rheumatoid arthritis, business, disease activity, Genetics and Molecular Biology(all)
Abstract: With great interest we read the viewpoint from Professor Landewe,1 calling for more caution, research and debate regarding the risks of overdiagnosis and overtreatment in rheumatology. Strongly agreeing with the overall message, especially that ‘(…) overtreatment is hardly discussed but likely present’, we would like to contribute to this discussion by raising an issue that touches base on two paradigms listed by Professor Landewe: remission and evidence-based rheumatology. There is now ample evidence that a substantial proportion (12%–38%) of patients with rheumatoid arthritis (RA) do not achieve the status of remission according to disease activity indices, solely because of a patient global assessment (PGA) score >1 (0–10 scale, 10=worst).2 3 If the elevated score on PGA does not reflect disease activity, additional immunosuppressive agents cannot improve the status of these patients, as inflammation is already essentially abrogated. Elevated PGA, therefore, may induce the risk of overtreatment when applying disease indices or Boolean-based criteria to define the treatment aim, which is remission or at least low disease activity (LDA) according to current treatment recommendations.4 5 Naturally, patients who still report relevant disease symptoms despite the absence of significant inflammation need …
Published: 2019

20. The frequency and influence of dementia risk factors in prodromal Alzheimer's disease

Author: Alexandre de Mendonça, Gerald Novak, Giovanni B. Frisoni, Philip Scheltens, Harald Hampel, Hilkka Soininen, Silvia Morbelli, Peter Johannsen, Alberto Lleó, Myriam Alexander, Ellis Niemantsverdriet, Mark Forrest Gordon, Solène Dauby, Mira Didic, Samantha Galluzzi, Angelika Wientzek, Rik Vandenberghe, Isabel Santana, Frans R.J. Verhey, Isabelle Bos, Yvonne Freund-Levi, Sebastiaan Engelborghs, Stephanie J.B. Vos, Alexander Drzezga, Wolfgang Maier, Johannes Kornhuber, Pieter Jelle Visser, Daniel Alcolea, Ellen Elisa De Roeck, Dina Silva, Inês Baldeiras, Jens Wiltfang, Oliver Peters, Anders Wallin, Eric Salmon, Sanna-Kaisa Herukka, E. Rüther, Magda Tsolaki, Preciosa M. Coloma, Christine Bastin, Lutz Frölich, Bart N.M. van Berckel, Åsa K. Wallin, Arto Nordlund, Flavio Nobili, Alzheimer's Disease Neuroimaging Initiative, Clinical sciences, Neurology, Educational Science, Faculty of Psychology and Educational Sciences, Maastricht University [Maastricht], Universität Heidelberg [Heidelberg] = Heidelberg University, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Georg-August-University = Georg-August-Universität Göttingen, Universität Bonn = University of Bonn, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Aristotle University of Thessaloniki, Karolinska Institutet [Stockholm], Copenhagen University Hospital, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hospital de la Santa Creu i Sant Pau, Université de Genève = University of Geneva (UNIGE), Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli studi di Genova = University of Genoa (UniGe), University of Cologne, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), VU University Medical Center [Amsterdam], Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, Centro Hospitalar e Universitário [Coimbra], Université de Lisbonne, University of Gothenburg (GU), F. Hoffmann-La Roche [Basel], Roche Products Ltd, Janssen Research & Development, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Lund University [Lund], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Eastern Finland, Repositório da Universidade de Lisboa, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), and School of Medicine / Clinical Medicine
Subjects: cognition, Male, Aging, MILD COGNITIVE IMPAIRMENT, ALCOHOL-CONSUMPTION, etiology [Alzheimer Disease], Disease, GUIDELINES, etiology [Cognitive Dysfunction], Alcohol Drinking/adverse effects, ddc:616.89, Cognition, 0302 clinical medicine, Cognitive decline, 10. No inequality, Alzheimer Disease/etiology, Depression (differential diagnoses), Medicine(all), Depression, General Neuroscience, Alzheimer's disease, Biomarkers, IWG-2 criteria, NIA-AA criteria, Prognosis, Risk factors, Neuroscience (all), Developmental Biology, Geriatrics and Gerontology, Neurology (clinical), ASSOCIATION, Middle Aged, CEREBROSPINAL-FLUID BIOMARKERS, 3. Good health, PREVALENCE, adverse effects [Alcohol Drinking], OBESITY, depression, Disease Progression, Female, Risk assessment, Psychology, medicine.medical_specialty, Alcohol Drinking, Hypercholesterolemia, DIAGNOSIS, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, Dementia, Cognitive Dysfunction, Cognitive Dysfunction/etiology, ddc:610, Obesity, Effects of sleep deprivation on cognitive performance, Psychiatry, METAANALYSIS, Aged, Proportional Hazards Models, DECLINE, 030214 geriatrics, Proportional hazards model, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, VASCULAR RISK, Human medicine, 030217 neurology & neurosurgery
Abstract: We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD., final draft, peerReviewed
Published: 2017

21. Features of Fecal and Colon Microbiomes Associate With Responses to Biologic Therapies for Inflammatory Bowel Diseases: A Systematic Review

Author: Cátia Rocha, Maria Manuela Estevinho, Joana Afonso, Fernando Magro, Francisco Portela, Eunice Trindade, Luis M. Correia, Laurent Peyrin-Biroulet, Paula Ministro, Gedii, Paula Lago, Federal University of Health Sciences of Porto Alegre = Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Instituto Superior Técnico, Universidade Técnica de Lisboa, Centro Hospitalar do Porto, Centro Hospitalar Tondela-Viseu, Centro Hospitalar e Universitário [Coimbra], Hospital de São João [Porto], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Portuguese Group of Studies in Inflammatory Bowel Disease, and Fundação para a Ciência e Tecnologia, Portugal, grant PDE/BDE/114583/2016 (C.R.)
Subjects: medicine.medical_specialty, Colon, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Gastroenterology, Vedolizumab, 03 medical and health sciences, Feces, 0302 clinical medicine, Internal medicine, Medicine, Humans, Microbiome, 10. No inequality, Crohn's disease, Hepatology, biology, business.industry, Adalimumab, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, Inflammatory Bowel Diseases, Crohn's Disease Activity Index, Ulcerative colitis, Infliximab, 3. Good health, Gastrointestinal Microbiome, Biological Therapy, Certolizumab, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Roseburia, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; BACKGROUND & AIMS:We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy.METHODS:We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods.RESULTS:From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia.CONCLUSIONS:In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
Published: 2019

22. International external quality assurance of JAK2 V617F quantification

Author: Julia Asp, Marta Vorland, Anni Aggerholm, Lasse Kjær, Karl Haslam, Elisabeth Oppliger Leibundgut, Rajko Kusec, Karolina Matiakowska, Robert Kralovics, Frank Dicker, Alessandro Pancrazzi, Morten Andersen, Lars Palmqvist, Sylvie Hermouet, Margarida Coucelo, Bruno Cassinat, Filippo Navaglia, Andrey Sudarikov, Aleksandar Eftimov, Vibe Skov, Thomas Kielsgaard Kristensen, François Girodon, Laurence Lodé, Niels Pallisgaard, Eric Lippert, Jiri Schwarz, Marzena Wojtaszewska, Hajnalka Andrikovics, Guy Wayne Novotny, Dorota Link-Lenczowska, Susanna Akiki, Melanie J. Percy, Dina Naguib, Beatriz Bellosillo, Department of Clinical Chemistry and Transfusion Medicine [Gothenburg, Sweden] (Institute of Biomedicine), University of Gothenburg (GU)-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Hematology [Roskilde, Denmark], Zealand University Hospital [Roskilde, Denmark], Department of Pathology [Barcelona, Spain], Hospital del Mar [Barcelona, Spain], Department of Pathology [Odense, Denmark], Odense University Hospital [Odense, Denmark], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Munich Leukemia Laboratory [Munich, Germany], Institute of Hematology and Blood Transfusion [Prague, Czech Republic], Department of Hematology and Bone Marrow Transplantation [Poznan, Poland], Poznan University of Medical Sciences [Poznan, Poland], Department of Laboratory Medicine and Pathology [Doha, Qatar], Qatar Rehabilitation Institute (QRI)-Hamad Bin Khalifa Medical City (HBKM), Aarhus University Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Bern [Bern, Switzerland] (University Hospital Bern ), Centro di Ricerca e Innovazione per le Malattie Mieloproliferative - CRIMM [ Florence, Italy], Haukeland University Hospital, University of Bergen (UiB), Central Hospital of Southern Pest [Budapest, Hungary], CeMM Research Center for Molecular Medicine [Vienna, Austria], Austrian Academy of Sciences (OeAW), Department of Internal Medicine I [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Service de Biologie Cellulaire [AP-HP, Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Hematology Unit, Hospital Pediátrico [Coimbra, Portugal], Centro Hospitalar e Universitário [Coimbra], Center for Biomolecular Pharmaceutical Analyses [Skopje, Republic of Macedonia] (Faculty of Pharmacy), University of Ss. Cyril and Methodius in Skopje, Macedonia (UKIM), St James’s Hospital [Dublin, Ireland], Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Molecular Diagnostics Laboratory [Krakow, Poland] (Hematology Diagnostics Department), Jagiellonian University Hospital [Krakow, Poland], Hématologie Biologique [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Faculty of Medicine [Bydgoszcz, Poland], Nicolaus Copernicus University [Toruń], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Laboratory Medicine [Padova, Italy], University - Hospital of Padova [Italy], Department of Hematology & Department of Pathology [Herlev, Denmark] (Molecular Unit), Herlev and Gentofte Hospital-University of Copenhagen = Københavns Universitet (KU), Belfast City Hospital [Belfast, UK], National Research Center for Hematology [Moscow, Russia], Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), RK acknowledges the support received by the Austrian Science Fund (FWF): F4702-B20 and P29018-B30., Bernardo, Elizabeth, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service de Biologie Cellulaire [Saint-Louis], Ss. Cyril and Methodius University in Skopje (UKIM), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Herlev and Gentofte Hospital-University of Copenhagen = Københavns Universitet (UCPH), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Male, medicine.medical_specialty, Standardization, Quality Assurance, Health Care, Computer science, media_common.quotation_subject, Mutation, Missense, [SDV.CAN]Life Sciences [q-bio]/Cancer, 610 Medicine & health, Real-Time Polymerase Chain Reaction, Real-Time Polymerase Chain Reaction/standards, Myeloproliferative neoplasms, 03 medical and health sciences, External quality assurance, JAK2 V617F, Quantitative PCR, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, medicine, Humans, Medical physics, Quality (business), Instrumentation (computer programming), Pathology, Molecular, media_common, Janus Kinase 2/genetics, business.industry, Amino acid substitution, Hematology, General Medicine, Janus Kinase 2, Amino Acid Substitution, Pathology, Molecular/standards, 030220 oncology & carcinogenesis, Female, business, Quality assurance, 030215 immunology
Abstract: IF 2.845; International audience; External quality assurance (EQA) programs are vital to ensure high quality and standardized results in molecular diagnostics. It is important that EQA for quantitative analysis takes into account the variation in methodology. Results cannot be expected to be more accurate than limits of the technology used, and it is essential to recognize factors causing substantial outlier results. The present study aimed to identify parameters of specific importance for JAK2 V617F quantification by quantitative PCR, using different starting materials, assays, and technical platforms. Sixteen samples were issued to participating laboratories in two EQA rounds. In the first round, 19 laboratories from 11 European countries analyzing JAK2 V617F as part of their routine diagnostics returned results from in-house assays. In the second round, 25 laboratories from 17 countries participated. Despite variations in starting material, assay setup and instrumentation the laboratories were generally well aligned in the EQA program. However, EQA based on a single technology appears to be a valuable tool to achieve standardization of the quantification of JAK2 V617F allelic burden.
Published: 2019

23. The Portuguese Rheumatoid Arthritis Impact of Disease (RAID) score and its measurement equivalence in three countries: validation study using Rasch Models

Author: Cátia Duarte, Joanne K. Nicklin, Ricardo J O Ferreira, Laure Gossec, J. A. P. Da Silva, Sarah Hewlett, Mwidimi Ndosi, Rheumatology Department [Coimbra, Portugal], Centro Hospitalar e Universitário [Coimbra], Health Sciences Research Unit: Nursing [Coimbra, Portugal] (UICiSA:E), Escola Superior de Enfermagem de Coimbra [Coimbra, Portugal], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Department of Nursing and Midwifery [Bristol, UK], University of the West of England [Bristol] (UWE Bristol), Academic Rheumatology Unit [Bristol, UK], University Hospitals Bristol, HAL UPMC, Gestionnaire, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Disease impact, RAID, Health-related quality of life, [SDV]Life Sciences [q-bio], Article, Cross-Cultural comparison, law.invention, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, law, Surveys and Questionnaires, Humans, Centre for Health and Clinical Research, 030212 general & internal medicine, Patient Reported Outcome Measures, Rheumatoid arthritis, Equivalence (measure theory), 030203 arthritis & rheumatology, Rasch model, Portugal, Debriefing, Public Health, Environmental and Occupational Health, Construct validity, Reproducibility of Results, Middle Aged, Cross-cultural studies, language.human_language, rheumatoid arthritis, health-related quality of life, patient-reported outcome measures, validation studies, cross-cultural comparison, disease impact, 3. Good health, [SDV] Life Sciences [q-bio], Comprehension, Validation studies, Research Design, Patient-reported outcome measures, language, Quality of Life, Female, Portuguese, Psychology, Clinical psychology
Abstract: Purpose The Rheumatoid Arthritis Impact of Disease (RAID) score assesses seven impact domains of interest for people with RA. This study aimed to test patients’ understanding of the Portuguese RAID and evaluate its cross-cultural validity for use in Portugal. Methods This was a mixed methods study comprising two phases: (i) cognitive debriefing to determine patient’s comprehension of the Portuguese RAID and (ii) cross-cultural validation using Rasch analysis. Construct validity was determined by fit to the model, invariance culture (compared with France and UK datasets) and evidence of convergent and divergent validity. Results Patients’ input (n = 38) led to minor changes in the phrasing of two items to ensure conceptual equivalence between the Portuguese and the original RAID. In Rasch analysis (n = 288), two items ‘Sleep’ and ‘Physical well-being’ in the Portuguese dataset did not adequately fit the model specifications, suggesting multidimensionality (sleep—not necessarily associated with RA) and redundancy (physical well-being overlapping with functional disability). Despite the imperfections, the scale had high internal consistency, evidence of convergent and divergent validity and invariance to culture (compared to France n = 195 and UK n = 205 datasets). The scale was well targeted for patients with different levels of disease impact. Conclusions The RAID has been successfully adapted into Portuguese and it can be used with confidence in clinical practice. Further research will be required to ensure it captures the full range of sleep problems in RA. Meanwhile, data across the three countries (Portugal, France and the UK) are comparable except for the two items (sleep and physical well-being). Electronic supplementary material The online version of this article (10.1007/s11136-018-1959-4) contains supplementary material, which is available to authorized users.
Published: 2018

24. Validity and reliability of the EULAR instrument RAID.7 as a tool to assess individual domains of impact of disease in rheumatoid arthritis: a cross-sectional study of 671 patients

Author: Gunnstein Bakland, Lena Bugge Nordberg, Siri Lillegraven, Espen A Haavardsholm, Erik Rødevand, Ulf Sundin, Nina Paulshus Sundlisater, Hallvard Fremstad, Tor Magne Madland, Åse Stavland Lexberg, Hilde Haukeland, Christian Høili, Hilde Stray, Anne Noraas Bendvold, Inger W Hansen, Gestionnaire, Hal Sorbonne Université, Centro Hospitalar e Universitário [Coimbra], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto = University of Porto, Diakonhjemmet Hospital, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Auteur indépendant, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidade do Porto, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, rheumatoid, RAID, Intraclass correlation, Cross-sectional study, [SDV]Life Sciences [q-bio], Immunology, Validity, Rheumatoid Arthritis, Severity of Illness Index, Etanercept, law.invention, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, law, medicine, Numeric Rating Scale, Humans, Immunology and Allergy, 030212 general & internal medicine, outcome assessment, 030203 arthritis & rheumatology, Sleep disorder, business.industry, Reproducibility of Results, Construct validity, medicine.disease, health care, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, arthritis, patient reported outcome measures, Physical therapy, Medicine, business, medicine.drug
Abstract: ObjectiveThe rheumatoid arthritis impact of disease (RAID) questionnaire comprises seven patient-important domains of disease impact (pain, function, fatigue, sleep disturbance, emotional well-being, physical well-being, coping). RAID was validated as a pooled-weighted score. Its seven individual items separately could provide a valuable tool in clinical practice to guide interventions targeting the patient’s experience of the disease. The aim was to separately assess the psychometric properties of each of the seven numeric rating scale (NRS) of the RAID (RAID.7).Material and methodsPost hoc analyses of data from the cross-sectional RAID study and from the Rainbow study, an open-label 12-week trial of etanercept in patients with RA. Construct validity of each NRS was assessed cross-sectionally in the RAID data set by Spearman’s correlation with the respective external instrument of reference. Using the rainbow data set, we assessed reliability through intraclass correlation coefficient between the screening and the baseline visits and responsiveness (sensitivity to change) by standardised response mean between baseline and 12 weeks.ResultsA total of 671 patients with RA with features of established disease were analysed, 563 and 108 from RAID and Rainbow, respectively. The NRS correlated moderately to strongly with the respective external instrument of reference (r=0.62–0.81). Reliability ranged from 0.64 (0.51–0.74) (pain) to 0.83 (0.76–0.88) (sleep disturbance) and responsiveness from 0.93 (0.73–1.13) (sleep disturbance) to 1.34 (1.01–1.64) (pain).ConclusionThe separate use of the individual NRS of RAID (RAID.7) is valid, feasible, reliable and sensitive to change, representing an opportunity to improve the assessment and treatment of disease impact with minimal questionnaire burden.Trial registration numberNCT00768053.
Published: 2021

25. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease

Author: Mathias Vilaine, Céline Garrec, Pierre Lindenbaum, Sophie Couvé, Mathilde Pacault, Laurence Heidet, Stéphane Bézieau, Celeste Bento, David Hoogewijs, Helene Dreau, Yannick Arlot-Bonnemains, Nelly Burnichon, Marion Lenglet, Richard van Wijk, Maria-Luigia Randi, Alexandre Buffet, Florence Robriquet, Fabrice Airaud, Holger Cario, Nicolas Janin, Melissa M. Pentony, Erika Kvikstad, Stéphane Richard, Karim Bouchireb, Antonis Kattamis, Jean-Michaël Mazzella, Carme Camps, Sylvie Job, Sophie Ferlicot, Anne Couturier, Richard Redon, Maria Caterina Putti, Thomas Besnard, Joachim R. Göthert, Klaus-Michael Debatin, Betty Gardie, Sophie Deveaux, Franck Chesnel, Solenne Dumont, Jenny C. Taylor, Marine Cornec, Bin Tean Teh, François Girodon, Vincent Bours, Sophie Gad, Anne-Paule Gimenez-Roqueplo, Sabine Irtan, Klaus Schwarz, Elpis Mantadakis, Samantha J. L. Knight, Brigitte Bressac-de Paillerets, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Universität Ulm - Ulm University [Ulm, Allemagne], Institute for Clinical Transfusion Medicine and Immunogenetics [Ulm, Germany], German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen, University of Oxford, Oxford NIHR Biomedical Research Centre, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Fribourg = University of Fribourg (UNIFR), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Oxford University Hospitals NHS Trust, Centre de Références Cancers Rares (PREDIR), INCA, Hôpital Bicêtre, Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Hôpitaux Universitaires Paris-Sud Bicêtre (APHP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] (MARHEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Sorbonne Paris Cité (USPC), Democritus University of Thrace (DUTH), Universitätsklinikum Ulm - University Hospital of Ulm, Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris-Saclay, National Heart Centre Singapore (NHCS), Service d'hématologie biologique [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, laboratory of Excellence GR-Ex, Paris, France, Università degli Studi di Padova = University of Padua (Unipd), C.H.U. Sart Tilman [Liège], University Medical Center [Utrecht], University Hospital [Essen, Germany], National and Kapodistrian University of Athens (NKUA), Cliniques Universitaires Saint-Luc [Bruxelles], Centro Hospitalar e Universitário [Coimbra], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Zürich Center for Integrative Human Physiology (ZIHP), Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Physiology, Faculté de Médecine, Université de Ngozi, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Oncologique [Villejuif], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Department of Medicine, Karolinska Institutet [Stockholm], National Haemoglobinopathy Reference Laboratory, Molecular Haematology, Haemophilia Centre, Churchill Hospital, John Radcliffe Hospital [Oxford University Hospital], Centre Expert National Cancer Rares PREDIR, Service d'Urologie, CHU de Bicêtre, Le Kremlin-Bicêtre, Service Genetique, 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), Service d’Anatomie Cytologie Pathologiques, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Pediatrics and Adolescent Medicine, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biologie et pathologie médicales [Gustave Roussy], Van Andel Research Institute, Grand Rapids, Michigan, Van Andel Institute [Grand Rapids], Service d'hématologie biologique (CHU de Dijon), Utrecht University [Utrecht], First Department of Paediatrics, Athens University, Thalassaemia Unit, 'Aghia Sofia' Children's Hospital, Centre Hospitalier Universitaire de Liège (CHU-Liège), SAFRAN Group, Service Génétique, Union nationale des coopératives d’élevage et d’insémination animale (UNCEIA), Rare Adrenal Cancer Network COMETE, CHATEL, Stephanie, University of Fribourg, and UCL - (SLuc) Centre de génétique médicale UCL
Subjects: 0301 basic medicine, Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Heterozygote, von Hippel-Lindau Disease, Adolescent, endocrine system diseases, Biochemistry, Immunology, Hematology, Cell Biology, RNA Splicing, [SDV]Life Sciences [q-bio], Medizin, Polycythemia, Biology, medicine.disease_cause, urologic and male genital diseases, 03 medical and health sciences, Exon, Young Adult, medicine, Humans, Genetic Predisposition to Disease, Von Hippel–Lindau disease, Child, Gene, neoplasms, Genetics, Mutation, Intron, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Exons, Middle Aged, medicine.disease, Exon skipping, female genital diseases and pregnancy complications, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], 030104 developmental biology, Von Hippel-Lindau Tumor Suppressor Protein, RNA splicing, Female, Synonymous substitution
Abstract: International audience; Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with von Hippel-Lindau disease, which is characterized by the development of highly vascularized tumors. Here, we identified a new VHL cryptic-exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identified mutations in E1' in seven families with erythrocytosis (one homozygous case and six compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in one large family with typical VHL disease but without any alteration in the other VHL exons. In this study we have shown that the mutations induced a dysregulation of the VHL splicing with excessive retention of E1' and are associated with a downregulation of VHL protein expression. In addition, we have demonstrated a pathogenic role for synonymous mutations in VHL-Exon 2 that alter splicing through E2-skipping in five families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially impact splicing, correlating with phenotype severity. This study demonstrates that cryptic-exon-retention or exon-skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research into the VHL-related-hypoxia-signaling pathway.
Published: 2018

26. The impact of patient global assessment in the definition of remission as a predictor of long-term radiographic damage in patients with rheumatoid arthritis: protocol for an individual patient data meta-analysis

Author: Ferreira, Ricardo, Welsing, Paco, Gossec, Laure, Jacobs, Johannes, Machado, Pedro, Ndosi, Mwidimi, Van Der Heijde, Désirée, da Silva, José, Centro Hospitalar e Universitário [Coimbra], University Medical Center [Utrecht], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), University College of London [London] (UCL), University of the West of England [Bristol] (UWE Bristol), and Leiden University Medical Center (LUMC)
Subjects: Outcome research, Time Factors, Remission, Near-remission, Radiographic damage, Prognosis, Individual patient datameta-analysis, Arthritis, Rheumatoid, Patient Outcome Assessment, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Humans, Disease activity, Rheumatoid arthritis, Function, Patient reported outcomes, Patient global assessment, Randomized Controlled Trials as Topic
Abstract: International audience; BACKGROUND: Remission is the target for management of rheumatoid arthritis (RA) and intensification of immunosuppressive therapy is recommended for those that do not achieve this status. Patient global assessment (PGA) is the single patient reported outcome considered in the American College of Rheumatology/European League Against Rheumatism remission criteria, but its use as target has been questioned. The primary aim of this study is to assess whether excluding PGA from the definition of disease remission changes the association of disease remission with long-term radiographic damage and physical function in patients with RA.METHODS: Individual Patient Data Meta-analysis using data from randomized controlled trials of biological and targeted synthetic agents, identified through ClinicalTrials.gov and PubMed. Different remission states will be defined: (i) 4v-remission [tender (TJC28) and swollen 28-joint counts (SJC28) both≤1, C-reactive protein (CRP)≤1 (mg/dl), and PGA≤1 (0-10 scale)], (ii) 4v-near-remission (TJC28≤1, SJC28≤1, CRP≤1, and PGA>1), (iii) non-remission (TJC28>1 or SJC28>1 or CRP>1), all mutually exclusive, and (iv) 3v-remission (TJC28≤1, SJC28≤1, CRP≤1). Likelihood ratios will be used to descriptively compare whether meeting the 3v and 4v-remission criteria in a single visit (at 6 or 12 months) predicts good outcome in the second year (1-2y). Differences in the predictive value of PGA in the definition of remission will be assessed by comparing the three mutually exclusive disease states using logistic regression analysis. Good outcome is defined primarily by radiographic damage (no deterioration in radiographic scores, whatever the instrument used in each trial), and secondarily by functional disability (Health Assessment Questionnaire consistently ≤0.5 and no deterioration), and their combination ("overall good outcome"). Additional analyses will consider longer periods over which to (concurrently) define remission status and outcome (between 1-5y and 1-10y), different cut-offs to define good radiographic outcome (change ≤0.5, ≤3 and ≤5 in radiographic score), sustained remission and the influence of treatment and other clinical factors.DISCUSSION: If 4v-remission and 4v-near-remission are associated with a similar probability of good outcomes, particularly regarding structural damage, the 3v-remission (excluding PGA) could be adopted as the target for immunosuppressive therapy. Patients' perspectives would remain essential, but assessed separately from disease activity, using instruments adequate to guide adjunctive therapies.
Published: 2018

27. Suppressing Inflammation in Rheumatoid Arthritis:Does Patient Global Assessment Blur the Target? A Practice-Based Call for a Paradigm Change

Author: Cátia Duarte, Ricardo J O Ferreira, Maarten de Wit, Mwidimi Ndosi, Laure Gossec, J. A. P. Da Silva, Centro Hospitalar e Universitário [Coimbra], University of the West of England [Bristol] (UWE Bristol), VU University Medical Center [Amsterdam], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ethics, Law & Medical humanities, and AII - Inflammatory diseases
Subjects: Male, medicine.medical_specialty, Cross-sectional study, Health Status, Clinical Decision-Making, Anti-Inflammatory Agents, Arthritis, Disease, Decision Support Techniques, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Predictive Value of Tests, Internal medicine, Humans, Medicine, Artrite Reumatóide, 030212 general & internal medicine, Depression (differential diagnoses), Aged, 030203 arthritis & rheumatology, Portugal, biology, business.industry, Remission Induction, C-reactive protein, Middle Aged, medicine.disease, 3. Good health, Inflamação, C-Reactive Protein, Cross-Sectional Studies, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Rheumatoid arthritis, Predictive value of tests, Physical therapy, biology.protein, Anxiety, Female, Joints, Inflammation Mediators, medicine.symptom, business, Biomarkers
Abstract: Objective: In current management paradigms of rheumatoid arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role. Methods: This was a cross-sectional, single-center study including consecutive ambulatory RA patients. Data collection comprised swollen 28-joint count (SJC28), tender 28-joint count (TJC28), C-reactive protein (CRP) level, PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorized using American College of Rheumatology/European League Against Rheumatism Boolean-based criteria: remission, near-remission (only PGA >1), and nonremission. A binary definition without PGA (3v-remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state. Results: A total of 309 patients were included (remission 9.4%, near-remission 37.2%, and nonremission 53.4%). Patients in near-remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in nonremission. In multivariable analyses, PGA in near-remission was explained (R2 adjusted = 0.50) by fatigue, pain, anxiety, and function. Fatigue and pain had no relationship with disease activity measures. Conclusion: In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP level ≤1) does not equate to low disease impact: a large proportion of these patients are considered in nonremission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This consideration suggests that clinical practice should be guided by 2 separate remission targets: inflammation (3v-remission) and disease impact.
Published: 2018

28. The controversy of using PGA to define remission in RA

Author: Maarten de Wit, Cátia Duarte, J. A. P. Da Silva, Ricardo J O Ferreira, Mwidimi Ndosi, Laure Gossec, Rheumatology, AII - Inflammatory diseases, Epidemiology and Data Science, APH - Methodology, CCA - Imaging and biomarkers, Centro Hospitalar e Universitário [Coimbra], University of Coimbra [Portugal] (UC), University of the West of England [Bristol] (UWE Bristol), VU University Medical Center [Amsterdam], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Ethics, Law & Medical humanities
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, Inflammation, medicine.medical_specialty, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Prostaglandins A, business.industry, Arthritis, Rheumatoid, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Internal medicine, Antirheumatic Agents, Medicine, Humans, business
Abstract: This is a response to "Views & News" by van Tuyl and Boers entitled "Remission - keeping the patient experience front and centre"; International audience
Published: 2018

29. Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy

Author: Fabian Hofmann, Alessandro Volpe, Peter F.A. Mulders, Lorenzo Marconi, Michael Staehler, Fiona Stewart, Markus A. Kuczyk, Thomas B. Lam, Börje Ljungberg, Thomas Powles, Milan Hora, Saeed Dabestani, John Norrie, Steven E. Canfield, Axel Bex, Axel S. Merseburger, Karim Bensalah, Centro Hospitalar e Universitário [Coimbra], Division of Molecular Biology, The Netherlands Cancer Institute, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charles University Hospital, Queen Mary University of London (QMUL), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Division of Urology, Amedeo Avogadro University of Eastern Piedmont, CCSD, Accord Elsevier, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pathology, medicine.medical_specialty, Percutaneous, Needle core biopsy, Urology, 030232 urology & nephrology, Diagnostic accuracy, Renal tumour, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Biopsy, Diagnosis, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, Renal mass, Accuracy, Fine-needle aspiration, [SDV.IB] Life Sciences [q-bio]/Bioengineering, medicine.diagnostic_test, business.industry, medicine.disease, 3. Good health, Meta-analysis, 030220 oncology & carcinogenesis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, business
Abstract: Item does not contain fulltext CONTEXT: The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety. OBJECTIVE: We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade. EVIDENCE ACQUISITION: Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (kappa) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2). EVIDENCE SYNTHESIS: A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (kappa=0.683) and a fair (kappa=0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien >/=2 complications was reported. Study limitations included selection and differential-verification bias. CONCLUSIONS: RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required. PATIENT SUMMARY: We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer.
Published: 2016

30. Malaria: looking for selection signatures in the human PKLR gene region

Author: Machado, Patricia, Pereira, Rui, Rocha, Ana Mafalda, Anco, Licínio, Fernandes, Natércia, Miranda, Juliana, Ribeiro, M. Letícia, Do Rosário, Virgílio E., Amorim, António, Gusmão, Leonor, Arez, Ana Paula, Malaria, Centre for Malaria and Tropical Diseases, Instituto de Higiene e Medicina Tropical (CMDT.LA/IHMT), Population Genetics, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Instituto de Medicina Legal, Universidade de Santiago de Compostela [Spain] (USC ), Sequencing Service, Anthropology, Centre of Research in Anthropology in Health, Universidade de Coimbra, Haematology, Centro Hospitalar e Universitário [Coimbra], Faculty of Medicine, Universidade Eduardo Mondlane, Central Hospital of Maputo, Paediatrics, and Paediatric Hospital David Bernardino
Subjects: parasitic diseases, Medicine
Abstract: International audience; The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. in vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations, from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.
Published: 2010

31. Tiotropium improves FEV in patients with COPD irrespective of smoking status

Author: Moita, J., Bárbara, C., Cardoso, J., Costa, R., Sousa, M., Ruiz, J., Santos, M.L., and Centro Hospitalar e Universitário [Coimbra]
Subjects: Medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2008

32. Evolving the comprehensive management of rheumatoid arthritis: identification of unmet needs and development of practical and educational tools

Author: Burmester, GR, Álvaro-Gracia, JM, Betteridge, N, Calvo Alén, J, Combe, B, Durez, P, Fautrel, B, Ferreira, RJO, Gabay, C, Iagnocco, A, Montecucco, C, Østergaard, M, Ramiro, S, Rubbert-Roth, A, Stamm, T, Szekanecz, Z, Taylor, PC, Van de Laar, M, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt-Universität zu Berlin, Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Universitario de Araba, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Cliniques Universitaires Saint-Luc [Bruxelles], Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centro Hospitalar e Universitário [Coimbra], University of Geneva [Switzerland], Università degli studi di Torino (UNITO), Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Copenhagen = Københavns Universitet (KU), Leiden University Medical Center (LUMC), Zuyderland Hospital [Heerlen, The Netherlands], Brustzentrum Kantonsspital St. Gallen, Medizinische Universität Wien = Medical University of Vienna, University of Debrecen, University of Oxford [Oxford], University of Twente [Netherlands], Psychology, Health & Technology, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: ddc:616, MESH: Arthritis, Rheumatoid, MESH: Humans, Arthritis, Rheumatoid/diagnosis/therapy, Europe, Humans, Surveys and Questionnaires, Arthritis, Rheumatoid, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid, MESH: Rheumatology, MESH: Europe, MESH: Surveys and Questionnaires
Abstract: OBJECTIVES: Despite availability of efficacious treatments, unmet needs still exist, preventing optimal and comprehensive management of rheumatoid arthritis (RA). Evolving the management of RA (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs. METHODS: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe. RESULTS: Five areas of priority need were identified: increasing early recognition of RA and treatment initiation; treating RA to target; optimal, holistic approach to selection of treatment strategy, including shared decision-making; improving identification and management of comorbidities; and non-pharmacological patient management. A suite of 14 eRA tools included educational slides, best-practice guidance, self‑assessment questionnaires, clinical checklists, a multidisciplinary team training exercise, an interactive patient infographic, and case scenarios. By April 2020, rheumatology professionals in 17 countries had been actively engaged in the eRA programme; in 11 countries, eRA tools were selected by national leaders in rheumatology and translated for local dissemination. A web platform, with country-specific pages, was developed to support access to the translated tools (https://www.evolvingthemanagementofra.com/). CONCLUSIONS: The eRA programme supports comprehensive management of RA across Europe through development and dissemination of practical educational tools. The eRA tools address priority needs and are available free of charge to the rheumatology community.

33. Comparison of different measuring methods in the assessment of the ISNT rule and its variants in a normal population: A cross-sectional study.

Author: Soares I, Gravito-Soares M, Gravito-Soares E, Vaz S, and Almeida V
Subjects: Humans, Cross-Sectional Studies, ROC Curve, Retinal Ganglion Cells, Intraocular Pressure, Tomography, Optical Coherence methods, Optic Disk
Abstract: Purpose: The aim of this study was to compare five different neuroretinal rim (NRR) measurement methods, based on quadrants and NRR widths, in the assessment of the ISNT (inferior (I) > superior (S) > nasal (N) > temporal (T)) rule, and its variants IST (inferior (I) > superior (S) > temporal (S)) rule, IS (inferior (I) > superior (S)) rule and T (temporal is the thinnest) rule in a normal population. Factors influencing compliance with this rule and its variants were also evaluated., Methods: Stereoscopic fundus images were analysed through a dichoptic viewing system. Two graders labelled the optic disc and cup, as well as the fovea. Custom-made software automatically determined the limits of the optic disc and cup and examined the ISNT rule and its variants using several NRR measurement methods., Results: Sixty-nine subjects with normal eyes were enrolled. For the various NRR measuring methods, the percentage of eyes following the rules, that is, validity ranges were 0.0%-15.9% for the ISNT rule, 31.9%-59.4% for the IST rule, 46.4%-59.4% for the IS rule and 50.7%-100.0% for the T rule. Significant intra-measurement agreement ranges were IST (κ = 0.50-0.85), IS (κ = 0.68-1.00) and T (κ = 0.24-0.77). Only the IST and IS rules achieved significant inter-measurement agreement (κ = 0.47-1.00). After multivariate and receiver operating characteristic (ROC) curve analyses, the vertical cup position cup y (area under the ROC curve (AUROC) = 0.60-0.96; cut-off = |0.005|) was the most important predictor for virtually all NRR measurement agreements for the ISNT, IST and IS rules. The horizontal cup position (AUROC = 0.50-0.92; cut-off = -0.028 to 0.05) was the most important predictive factor for the majority of the NRR measurement agreements for the T rule., Conclusions: Only the IST and IS rules are valid for the same normal subjects. The most important factor affecting the validity of the ISNT rule and its variants was the anatomical cup position. NRR measurement agreements based on NRR quadrants exhibited larger validity and better agreement. The IST and IS rules can be combined with the alternative SIT (superior (S) > inferior (I) > temporal (T)) and SI (superior (S) > inferior (I)) rules to detect almost all normal subjects., (© 2023 College of Optometrists.)
Published: 2023
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34. An Immunohistochemical Study of Breast Cancer Brain Metastases: The Role of CD44 and AKT in the Prognosis.

Author: Martins Gama J, Caetano Oliveira R, Teixeira P, Silva F, Abrantes C, Figueiredo P, Simões S, Rebelo O, and Cipriano MA
Subjects: Humans, Female, Proto-Oncogene Proteins c-akt, Retrospective Studies, Biomarkers, Tumor metabolism, Hyaluronan Receptors, Breast Neoplasms pathology, Brain Neoplasms
Abstract: Breast cancer is a major health burden, and up to one-third of patients with breast cancer develop brain metastases, which are linked to a very poor prognosis. Few biomarkers are available to predict the prognosis of patients with metastases. Assessment by immunohistochemistry may be used as a tool to predict the behavior of these tumors. A retrospective transversal study including 114 patients (diagnosed between 2000 and 2016) with breast cancer brain metastases was carried out using archival biological material from 114 patients with breast cancer brain metastases. Expression of CD44, HER2, ER, PR, CA9, PDL-1, CD133, ALDH1, PTEN, AKT, PI3K, and AR markers was assessed by immunohistochemistry. The overexpression of CD44 and AKT was associated with worse overall survival ( P =0.047 and P =0,034, respectively), on univariate analysis, in the cohort of parenchymal and bone metastases; the impact of AKT expression was also evident in the parenchymal cohort on uni ( P =0.021) and multivariate analysis ( P =0.027). The remaining markers did not exhibit a statistical correlation. Immunohistochemistry markers such as CD44 and AKT may have a prognostic impact on survival in patients with breast cancer brain metastases. The conjugation with other markers may help with the stratification of patients and therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2023
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35. Reply on: International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia.

Author: Kundakci B, Hall M, Atzeni F, Branco J, Buskila D, Clauw D, Crofford LJ, Fitzcharles MA, Georgopoulos V, Gerwin RD, Kosek E, Macfarlane GJ, Neal C, Rudin NJ, Ryan S, da Silva JAP, Taylor AM, Turk DC, Whibley D, Doherty M, Zhang W, and Abhishek A
Subjects: Humans, Delphi Technique, Consensus, Fibromyalgia
Published: 2023
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36. International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia.

Author: Kundakci B, Hall M, Atzeni F, Branco J, Buskila D, Clauw D, Crofford LJ, Fitzcharles MA, Georgopoulos V, Gerwin RD, Kosek E, Macfarlane GJ, Neal C, Rudin NJ, Ryan S, da Silva JAP, Taylor AM, Turk DC, Whibley D, Doherty M, Zhang W, and Abhishek A
Subjects: Humans, Consensus, Delphi Technique, Canada, Fatigue etiology, Fatigue therapy, Pain, Fibromyalgia therapy, Sleep Wake Disorders
Abstract: Objectives: To develop evidence-based expert recommendations for non-pharmacological treatments for pain, fatigue, sleep problems, and depression in fibromyalgia., Methods: An international, multidisciplinary Delphi exercise was conducted. Authors of EULAR and the Canadian Fibromyalgia Guidelines Group, members of the American Pain Society and clinicians with expertise in fibromyalgia were invited. Participants were asked to select non-pharmacological interventions that could be offered for specific fibromyalgia symptoms and to classify them as either core or adjunctive treatments. An evidence summary was provided to aid the decision making. Items receiving >70% votes were accepted, those receiving <30% votes were rejected and those obtaining 30-70% votes were recirculated for up to two additional rounds., Results: Seventeen experts participated (Europe (n = 10), North America (n = 6), and Israel (n = 1)) in the Delphi exercise and completed all three rounds. Aerobic exercise, education, sleep hygiene and cognitive behavioural therapy were recommended as core treatments for all symptoms. Mind-body exercises were recommended as core interventions for pain, fatigue and sleep problems. Mindfulness was voted core treatment for depression, and adjunctive treatment for other symptoms. Other interventions, namely music, relaxation, hot bath, and local heat were voted as adjunctive treatments, varying between symptoms., Conclusions: This study provided evidence-based expert consensus recommendations on non-pharmacological treatments for fibromyalgia that may be used to individualise treatments in clinical practice targeting the diverse symptoms associated with fibromyalgia., Competing Interests: Declaration of Competing Interest FA reports grants/contracts from BMS, Celgene, Novartis and Sandoz; consulting fees from AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and Sanofi-Aventis. LC reports grants/contracts from NIH/NIAMS; participation on a data safety monitoring/advisory board for NIH/NIAMS; a leadership/fiduciary role with American College of Rheumatology. MAF reports expert testimony for the plaintiff and the defendant; leadership/fiduciary role with Health Canada, Australian Centre for Cannabinoid Clinical and Research Excellence, Arthritis Foundation US, Canadian Rheumatology Association, American College of Rheumatology abstract committee. EK reports royalties/licenses for studentlitteratur and liber; consulting fees from Eli Lilly; leadership/fiduciary role with IASP Terminology Task Force and IASP ICD-11 Task Force. SR reports grants/contracts from General Nursing Council Trust, Haywood Foundation and CRN. JAPS reports grants/contracts from Pfizer; payment/honoraria from Eli Lilly and Amgen; participation on a data safety monitoring/advisory board for Eli Lilly and Abbvie; and owner of MyFibromyalgia.org. AT reports consulting fees from Pfizer. RG reports leadership/fiduciary roles with International Myopain Society. DW reports grants/contracts from Versus Arthritis Foundation and Michigan Medicine Dan Barry., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2022
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37. Lymphoma presented as dysphagia: a diagnosis hard to swallow.

Author: João M, Bento-Miranda M, Gravito-Soares E, Gravito-Soares M, and Figueiredo P
Subjects: Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Female, Fluorodeoxyglucose F18 therapeutic use, Humans, Positron-Emission Tomography, Prednisone therapeutic use, Rituximab therapeutic use, Vincristine therapeutic use, Deglutition Disorders etiology, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy
Abstract: An 18-year-old woman presented with progressive oesophageal dysphagia, weight loss and night sweats over a 6-month period. Oesophagogastroduodenoscopy revealed a diffuse luminal narrowing with normal mucosa, whose biopsies were inconclusive. A cervical and thoracic CT scan showed a thickening of the upper oesophagus, densification of the mediastinal fat, several adenopathies and a 4.3×2.4 cm mass with infiltrative appearance and heterogeneous enhancement in right cervical paravertebral location. Positron emission tomography-CT showed marked increased fluorodeoxyglucose uptake in supradiaphragmatic lymph nodes, pleuropulmonary tissue, paraspinal musculature and bone marrow. Imaging-guided and surgical incisional biopsies of the paravertebral mass were inconclusive. During hospitalisation, she developed right cervicobrachial paraesthesia. Only excisional biopsy of the mass allowed the diagnosis of high-grade B-cell lymphoma not otherwise specified, Ann Arbor stage IV-B. The patient underwent chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), followed by R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride). Follow-up at 12 months revealed complete response., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2021
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38. Ischemic Cerebellar Stroke in a 4-Year-Old Boy After Chickenpox: An Atypical Vascular Involvement.

Author: Marques P, Pereira C, Silva F, Garcia T, and Ribeiro JA
Subjects: Anticoagulants therapeutic use, Antiviral Agents therapeutic use, Cerebral Arteries diagnostic imaging, Chickenpox complications, Chickenpox diagnosis, Chickenpox drug therapy, Child, Preschool, Glucocorticoids therapeutic use, Host-Pathogen Interactions, Humans, Ischemic Stroke diagnostic imaging, Ischemic Stroke drug therapy, Male, Treatment Outcome, Vertebrobasilar Insufficiency diagnostic imaging, Vertebrobasilar Insufficiency drug therapy, Cerebellum blood supply, Cerebral Arteries virology, Chickenpox virology, Herpesvirus 3, Human pathogenicity, Ischemic Stroke virology, Vertebrobasilar Insufficiency virology
Abstract: Cerebrovascular events in pediatric population are very rare. Up to 30% may result from varicella zoster (VZV) arteriopathy, usually as a delayed complication of varicella primary infection. The most typical pattern includes involvement of anterior brain circulation arteries, probably by VZV migration from the trigeminal ganglia. Strokes related with VZV usually have a good prognosis, but risk of recurrence is greater when compared to other stroke etiologies in this age group. We report the case of a 4-year-old boy, immunocompetent, who presented a basilar artery stenosis and a cerebellar stroke, an extremely rare presentation of VZV arteriopathy. The investigation workup and treatment are detailed, as the clinical and imaging follow-up after one year., (Copyright © 2021 Elsevier Inc. All rights reserved.)
Published: 2021
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39. Pseudoaneurysm of the gastroduodenal artery with arterio-duodenal fistulization secondary to acute pancreatitis: an unusual endoscopic diagnosis.

Author: Macedo C, Gravito-Soares E, and Gravito-Soares M
Subjects: Acute Disease, Gastrointestinal Hemorrhage, Hepatic Artery, Humans, Aneurysm, False complications, Aneurysm, False diagnostic imaging, Pancreatitis complications, Pancreatitis diagnostic imaging
Abstract: Not applicable.
Published: 2021
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40. Safety and Effectiveness of Biologic Disease-Modifying Antirheumatic Drugs in Older Patients with Rheumatoid Arthritis: A Prospective Cohort Study.

Author: Freitas R, Godinho F, Madeira N, Fernandes BM, Costa F, Santiago M, Neto A, Azevedo S, Couto M, Sequeira G, Dias JM, Bernardes M, Miranda L, Pereira JP, Fonseca JE, and Santos MJ
Subjects: Adult, Age Factors, Aged, Antibodies, Monoclonal adverse effects, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid epidemiology, Biological Products adverse effects, Cohort Studies, Comorbidity, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Portugal, Prospective Studies, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Biological Products therapeutic use
Abstract: Background and Objective: The number of older patients with rheumatoid arthritis is increasing, but data on drug effectiveness and safety in these patients are scarce. This study assessed the effectiveness and safety of biologic disease-modifying antirheumatic drugs in older patients with rheumatoid arthritis., Methods: This prospective cohort study was based on data recorded in the Rheumatic Diseases Portuguese Register (Reuma.pt). Treatment persistence, European League Against Rheumatism response at 6 and 12 months, and adverse events were compared between adult (age < 65 years), old (age 65-74 years), and very old (age ≥ 75 years) patients., Results: In total, 2401 patients were included, of which 379 were old and 83 were very old. Older patients had higher disease activity at baseline (Disease Activity Score 28: 5.5 in adults, 5.7 in old patients, and 6 in very old patients; p = 0.02) and more comorbidities, with patients aged 65-74 years beginning biologic disease-modifying antirheumatic drugs later in the course of rheumatoid arthritis. Treatment persistence was similar in the three patient groups (p = 0.07). The European League Against Rheumatism response rates were comparable in the three groups at 6 months (81.6% of adults, 75.2% of old patients, and 81.8% of very old patients; p = 0.19), and inferior in old patients at 12 months. The proportion of patients who experienced adverse events was also similar in the three groups (21% of adults, 22.5% of old patients, and 22.9% of very old patients; p = 0.76), but the rate of serious adverse events was higher in old patients (1.94/100 patient-years) and very old patients (4.29/100 patient-years) compared with 1.03/100 patient-years in adult patients with rheumatoid arthritis (p < 0.05)., Conclusions: Adults, old patients, and very old patients with rheumatoid arthritis benefit similarly from biologic disease-modifying antirheumatic drug treatments, although older patients have more active disease at baseline and more comorbidities. However, it is necessary to consider the risk of serious adverse events in older patients when prescribing a biologic.
Published: 2020
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41. Airway management in a patient with Crouzon syndrome proposed to orthognathic surgery.

Author: Fernandes M, Eufrásio A, Bonifácio J, and Marcelino J
Subjects: Adult, Airway Obstruction surgery, Female, Humans, Treatment Outcome, Airway Management methods, Craniofacial Dysostosis surgery, Orthognathic Surgical Procedures methods, Osteotomy, Le Fort methods
Abstract: Airway management is one of the most important anaesthetist's skills as major complications of airway management, although rare, can be among the most life threatening in medicine. Crouzon syndrome is a rare condition with physical characteristics that can result in difficult airway manipulation. A correct preanaesthetic evaluation and a planned preinduction strategy should be designed to facilitate intubation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Published: 2018
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42. Small-Bowel Diverticulosis: Enteroscopic Diagnosis of an Unusual Cause of Overt Small Bowel Bleeding.

Author: Gravito-Soares E, Gravito-Soares M, and Figueiredo P
Subjects: Aged, 80 and over, Double-Balloon Enteroscopy, Histocytochemistry, Humans, Male, Microscopy, Diverticulum diagnosis, Diverticulum pathology, Gastrointestinal Hemorrhage etiology, Gastrointestinal Hemorrhage pathology, Intestinal Diseases diagnosis, Intestinal Diseases pathology, Jejunum pathology
Published: 2018
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43. Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration.

Author: Hogg RE, Silva R, Staurenghi G, Murphy G, Santos AR, Rosina C, and Chakravarthy U
Subjects: Age Factors, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Male, Middle Aged, Tomography, Optical Coherence, Visual Acuity, Choroidal Neovascularization pathology, Macular Degeneration pathology, Retinal Drusen diagnosis
Abstract: Purpose: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function., Design: Cohort study., Participants: We recruited 105 patients (age range, 52-93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe., Methods: Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts., Main Outcome Measures: Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume., Results: Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1-28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline., Conclusions: Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Published: 2014
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44. Choroidal thickness after treatment for myopic  choroidal neovascularization.

Author: Farinha CL, Baltar AS, Nunes SG, Franqueira NF, Figueira JP, Pires IA, Cachulo ML, and Silva RM
Subjects: Adult, Age Factors, Aged, Aged, 80 and over, Axial Length, Eye pathology, Choroidal Neovascularization physiopathology, Cross-Sectional Studies, Female, Fluorescein Angiography, Humans, Male, Middle Aged, Myopia, Degenerative physiopathology, Organ Size, Ranibizumab, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity physiology, Angiogenesis Inhibitors therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Choroid pathology, Choroidal Neovascularization drug therapy, Myopia, Degenerative drug therapy, Photochemotherapy
Abstract: Purpose: To evaluate choroidal thickness in highly myopic eyes with choroidal neovascularization (CNV), 3 or more years after treatment with photodynamic therapy (PDT), intravitreal ranibizumab (IVR), or both (PDT + IVR)., Methods: The medical records of patients with high myopia and CNV treated with PDT or IVR in our department were reviewed. Eyes meeting the inclusion criteria were assigned to 3 groups: PDT, IVR, and PDT + IVR. A fourth group, "dry myopic maculopathy," included the contralateral highly myopic eyes that never developed CNV. All patients performed a cross-sectional evaluation with best-corrected  visual acuity (BCVA), measurement of axial length, color fundus photography, and enhanced depth imaging with spectral domain optical coherence tomography., Results: Forty-two eyes (21 patients) were included: 11 eyes (26.2%) in the PDT group, 8 (19.0%) in the IVR group, 9 (21.4%) in the PDT + IVR group, and 14 (33.3%) in the dry maculopathy group. Subfoveal choroidal thickness showed no significant differences between groups (p>0.05). Positive correlation was found between BCVA and macular choroidal thickness (r = +0.293, p<0.001). Regression analysis showed that age (p<0.001), axial length (p<0.001), sex (p = 0.001), and myopic lesions such as tessellated fundus (p = 0.046) and patchy atrophy (p = 0.008) were predictive of choroidal thickness. Type of treatment was not predictive of choroidal thickness., Conclusions: Older age and greater axial length are the major factors associated with macular choroidal thinning in highly myopic eyes submitted to CNV treatment. The type of treatment performed for myopic CNV had no predictive contribution for choroidal thickness.
Published: 2013
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