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Introduction: The 2017 reform of the third cycle of medical studies (R3C) was accompanied by modifications in the formats and number of specialty diplomas. The aim of this study was to investigate the evolution of the choice of the internal medicine and clinical immunology specialty before and after 2017., Methods: We used the median ranking and its evolution, as well as incoming and outgoing remorse rights, as markers of attractiveness. Data on the number of position offered, rankings and affectation were collected from decrees published in the French "Journal Officiel" each year. A survey conducted by the "Amicale des Jeunes Internistes" investigated the reasons for the outgoing or incoming rights to remorse., Results: Before 2017, internal medicine was accessible to 52% of students on average, with a median rank of 1118 [339-2640]. From 2017 onwards, the internal medicine specialty was accessible to an average of 76.6% of students, with a median rank of 2772 [1039-5155]. The balance of incoming and outgoing remorse rights was -4.7% before 2017 and varied between -4.1 and -12.4% from 2017., Conclusion: Since 2017, the median and cut-off ranks of students choosing internal medicine specialty have increased, and balance of incoming and outgoing remorse rights was increasingly negative. A reflection on the attractiveness of the internal medicine specialty is undertaken by the National College of Internal Medicine Teachers in order to make the richness of the specialty and its different modes of practice known to future residents., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this prospective study was to evaluate the tolerance and feasibility of using virtual reality headsets with patients during interventional radiology procedures., Material and Method: In this single-center prospective study, the use of a virtual reality headset in addition to the usual analgesic and anxiolytic treatment was proposed to all patients presenting in the interventional radiology department from December 2020 to June 2022. Exclusion criteria were as follows: (1) patients with whom it was not possible to communicate (2) epileptic patients, (3) non-verbal patients, and (4) pregnant women. The main objective was to evaluate the safety of the procedure by screening complications during and after the procedure. The second objective was to evaluate feasibility, as defined by the number of patients using the helmet until the end of the procedure. Effectiveness (patient's self-evaluation of pain and anxiety), comfort, satisfaction, emotions felt, sense of security, and feeling of immersion were also evaluated. Caregivers completed a feedback questionnaire., Results: Virtual reality headsets were offered to 100 patients, 9 of whom declined. Procedures were achieved in 93.5% of cases: 6/91 patients removed the headset before the end of the procedure. There were minor adverse events in 2/85 (2.3%) procedures (discomfort and nausea) and no major adverse events. 93.9% of patients found an overall benefit, and 90.2% would recommend virtual reality to another patient. 94.4% of caregivers were satisfied with the virtual reality equipment. The mean pain level was 2.5 ± 2.7 before the procedure, 3.3 ± 2.5 during the procedure, and 1.6 ± 2.7 after the procedure. Mean anxiety scores were 4.6 ± 2.9 before the procedure, 3.1 ± 2.7 during the procedure, and 1.1 ± 1.9 after the procedure., Conclusion: The use of virtual reality technology as a complement to traditional therapy for procedures under local anesthesia is feasible and safe in interventional radiology and can be beneficial for pain and anxiety management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people., Method: We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score., Results: From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05)., Conclusion: Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The 2017 reform of the 3rd cycle of medical studies introduced the concept of supervised autonomy with the creation of a new junior doctor (JD) status. The aim of this work was to interview the first class of JDs in internal medicine and clinical immunology (IMCI) regarding the progress and implementation of this final year of internship., Methods: The IMCI JDs were invited to complete an anonymous online survey, contacted by email and social networks., Results: The questionnaire received 36 responses out of an estimated fifty JDs. The majority of JDs spent more than 70% of their time on conventional hospitalisation and less than 20% on scheduled hospitalisation. Most of them would have preferred to do more consultations and provide expert counsels. Weekly working hours were not respected for the majority of JDs. Personal education and academic formation were not respected for 77.8% of JDs. Overall, 75% were satisfied with their empowerment and 88.6% felt that the transition to post residency would be easier with the consolidation phase. A third reported that their residency had confirmed their apprehension about practising as an internist, and even that this apprehension might call into question their future practice., Conclusion: This survey is an initial assessment of the implementation of the JD year in the IMCI residency. A collective effort around this last year of internship seems to be essential to ensure the personal and professional development of young internists., (Copyright © 2023 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Herbicides cause oxidative stress in nontarget microorganisms, which may exhibit adaptive responses to substances they have not previously encountered. Nevertheless, it is unclear whether these characteristics occur in bacteria isolated from agricultural soil. Two possible adaptation strategies of Stenotrophomonas sp. CMA26 was evaluated in agricultural soil in Brazil, which is considered stressful due to the intense use of pesticides. The study focused on degradation and antioxidant enzymes in response to the herbicide Heat, which was absent at the isolation site. The results indicated that higher concentrations of herbicide led to more intense stress conditions during the initial periods of growth. This was evidenced by elevated levels of malondialdehyde and peroxide, as well as a significant reduction in growth. Our data show that herbicide degradation is a selection-dependent process, as none of the 35 isolates from the same environment in our collection were able to degrade the herbicide. The stress was controlled by changes in the enzymatic modulation of catalase activity in response to peroxide and glutathione S-transferase activity in response to malondialdehyde, especially at higher herbicide concentrations. This modulation pattern is related to the bacterial growth phases and herbicide concentration, with a specific recovery response observed during the mid phase for higher herbicide concentrations. The metabolic systems that contributed to tolerance did not depend on the specific prior selection of saflufenacil. Instead, they were related to general stress responses, regardless of the stress-generating substance. This system may have evolved in response to reactive oxygen species, regardless of the substance that caused oxidative stress, by modulating of the activities of various antioxidant enzymes. Bacterial communities possessing these plastic tolerance mechanisms can survive without necessarily degrading herbicides. However, their presence can lead to changes in biodiversity, compromise the functionality of agricultural soils, and contribute to environmental contamination through drift., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Osteoarthritis is a chronic pathology that involves multidisciplinary management. Self-management for patients is an essential element, present in all international guidelines. During the time of the spa therapy, the patient is receptive to take the advantage of self-management workshops. The aim of this study is to assess the effects of 18 days spa therapy associated with a self-management intervention in patients with knee osteoarthritis in comparison with spa therapy alone on a priority objective, personalized and determined with the patient, chosen in the list of 5 objectives determined during the self-management initial assessment., Methods and Analysis: Two hundred fifty participants with knee osteoarthritis will participate to this multicenter, prospective, randomized, controlled study. All patients will benefit 18 days of spa therapy and patients randomized in the intervention group will participate to 6 self-management workshops. Randomization will be centralized. The allocation ratio will be 1:1. Data analysts and assessor will be blinded. The primary outcome is the effectiveness of the educational workshops associated with spa therapy in comparison with spa therapy alone on a priority objective, measured by Goal Attainment Scaling (GAS). The secondary outcomes are disability, health-related quality of life, and pain intensity., Ethics and Dissemination: Ethics were approved by the CPP Sud-Méditerranée II. The results will be disseminated in a peer-reviewed journal and disseminated at PRM, rheumatology, and orthopedics conferences. The results will also be disseminated to patients., Trial Registration: Trial registration number NCT03550547. Registered 8 June 2018. Date and version identifier of the protocol. Version N°6 of March 12, 2018., (© 2022. The Author(s).)

Objective: To develop and validate a patient knowledge questionnaire regarding axial spondyloarthritis (axSpA)., Methods: Knowledge considered essential for patients with axSpA was identified through Delphi rounds among rheumatologists, healthcare professionals (HCPs), and patients, then reformulated to develop the knowledge questionnaire. Cross-sectional validation was performed in 14 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin concordance correlation coefficient), and sensitivity to change (knowledge score before vs after patient education sessions and effect size)., Results: The Spondyloarthritis Knowledge Questionnaire (SPAKE) is a self-administered 42-item questionnaire with a 32-item short form, both scored 0 to 100, assessing knowledge of disease, comorbidities, pharmacological treatments, nonpharmacological treatments, self-care, and adaptive skills. In the validation study (130 patients; 67 [51.5%] male, mean age 43.5 [SD 12.9] yrs), the mean (SD) score of the long-form questionnaire was 71.6 (15.4), with higher scores (better knowledge) in nonpharmacological treatments and adaptive skills and lower scores in cardiovascular comorbidity and pharmacological treatments. Acceptability was good, with no missing data; the internal validity coefficient was 0.85. Reproducibility was good (0.81, 95% CI 0.72-0.89). SPAKE showed good sensitivity to change; scores were 69.2 (15.3) then 82.7 (14.0) after patient education sessions (Hedges effect size = 0.92, 95% CI 0.52-1.31)., Conclusion: SPAKE is a knowledge questionnaire for patients with axSpA, developed with the involvement of HCPs and patients and reflecting current recommendations for the management of axSpA. SPAKE will be useful in assessing knowledge acquisition and self-management strategies in routine care and research., (Copyright © 2023 by the Journal of Rheumatology.)

Introduction: The aim of this retrospective monocentric study was to assess the safety and efficacy of spontaneous soft-tissue hematoma transarterial embolization (TAE) and to evaluate predictive factors for early mortality (≤30 days) after TAE for spontaneous soft-tissue hematoma (SSTH)., Materials and Methods: Between January 2010 and March 2022, all patients referred to our hospital for spontaneous soft-tissue hematoma and treated by emergency TAE were reviewed. Inclusion criteria were patients: ≥18-year-old, with active bleeding shown on preoperative multidetector row computed tomography, with spontaneous soft-tissue hematoma, and treated by TAE. Exclusion criteria were patients with soft-tissue hematomas of traumatic, iatrogenic, or tumoral origin. Clinical, biological, and imaging records were reviewed. Imaging data included delimitation of hematoma volume and presence of fluid level. Univariate and multivariate analyses were performed to check for associations with early mortality., Results: Fifty-six patients were included. Median age was 75.5 [9-83] ([Q1-Q3] years and 23 (41.1%) were males. Fifty-one patients (91.1%) received antiplatelet agent and/or anticoagulant therapy. All 56 patients had active bleeding shown on a preoperative CT scan. Thirty-seven (66.0%) hematomas involved the retroperitoneum. Median hemoglobin level was 7.6 [4.4-8.2] g/dL. Gelatine sponge was used in 32/56 (57.1%) procedures. Clinical success was obtained in 48/56 (85.7%) patients and early mortality occurred in 15/56 (26.8%) patients. In univariate and multivariate analysis, retroperitoneal location and volume of hematoma were associated with early mortality., Conclusion: Retroperitoneal location and volume of hematoma seem to be risk factors for early death in the context of TAE for spontaneous soft-tissue hematoma. Larger multicenter studies are necessary to identify others predictive factors for early mortality and to anticipate which patients may benefit from an interventional strategy with TAE.

Purpose: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis., Source: A systematic review and a meta-analysis were conducted to identify and assess randomised control trials and observational studies with prospective enrolment that included trauma patients and compared adjustment of LMWH thromboprophylaxis versus no adjustment. The primary and secondary endpoints were VTE and bleeding, respectively. The Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated using the Mantel-Haenszel method., Principal Findings: Nine studies were included in the meta-analysis. No significant reduction in the risk of VTE was observed with adjusted doses of LMWH compared with fixed doses when considering only randomised control trials (OR 1.02 [95% CI, 0.09 to 11.6]) or all trials (OR 0.70 [95% CI, 0.34 to 1.42]). Similarly, there was no significant difference in bleeding risk (OR 1.36, 95% CI 0.59 to 3.10)., Conclusion: This meta-analysis shows that, to date, there is no evidence to justify adjusting LMWH doses, in agreement with the recommendations of the American College of Chest Physicians., (Copyright © 2022 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0-100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with < 5% missing data. Internal validity coefficient was 0.90. Mean (standard deviation) long-form score was 72.8 ± 17.8, with lower scores in comorbidity and self-care and higher scores in adaptive skills. Reproducibility was good (0.86 [0.80; 0.92]). RAKE score was positively correlated with the patients' level of education and the HPs' opinion on the patients' knowledge. RAKE score showed good sensitivity to change: 66.8 ± 16.4 then 83.8 ± 12.7, representing a hedges effect size of 1.14 [95% CI 0.73; 1.55]. RAKE is an updated questionnaire assessing essential knowledge for patients with RA to enhance self-management according to current guidelines and the patients' perspective. RAKE can usefully inform patient education interventions, routine care and research., (© 2022. The Author(s).)

Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020-July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective. Overall, these studies are consistent in showing that NSAIDs neither increase the likelihood of SARS-CoV-2 infection nor worsen outcomes in patients with COVID-19. This is reflected in current recommendations from major public health authorities across the world, which support NSAID use for analgesic or antipyretic treatment during COVID-19. Thus, there is no basis on which to restrict or prohibit use of these drugs by consumers or patients to manage their health conditions and symptoms during the pandemic., (© 2022. The Author(s).)

Background: Mobile health applications (apps) are increasing in interest to enhance patient self-management. Few apps are actually used by patients and have been developed for patients with inflammatory arthritis (IA) treated with disease-modifying anti-rheumatic drugs which use entails risk of adverse effects such as infections., Objective: To develop Hiboot, a self-management mobile app for patients with IA, by using a user-centred step-by-step approach and assess its real-life use., Methods: The app development included first a qualitative study with semi-guided audiotaped interviews of 21 patients to identify the impact of IA on daily life and patient treatments practices and an online cross-sectional survey of 344 patients to assess their health apps use in general and potential user needs. A multidisciplinary team developed the first version of the app via five face-to-face meetings. After app launch, a second qualitative study of 21 patients and a users' test of 13 patients and 3 rheumatologists led to the app's current version. The number of app installations, current users and comments were collected from the Google Play store and the Apple store., Results: The qualitative study revealed needs for counselling, patient-health professional partnership, and skills to cope with risk situations; 86.8% participants would be ready to use an app primarily on their rheumatologist's recommendation. Six functionalities were implemented: a safety checklist before treatment administration, aids in daily life situations based on the French academic recommendations, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary. The Hiboot app was installed 20,500 times from September 2017 to October 2020, with 4300 regular current users. Scores were 4.4/5 stars at Android and iOS stores., Conclusion: Hiboot is a free self-management app for patients with IA developed by a step-by-step process including patients and health professionals. Further evaluation of the Hiboot benefit is needed., Competing Interests: CB, TP, AL, CV, GD, PB, SD, FT, DL, LG, FAL, MA, SP and JS declare no competing interests in relation is this study. SG, FM were paid by Unknowns Research department for their contribution to the study. GM, JLC, MQ, were employed by Unknowns Conseil en stratégie et innovation, Paris, France HJ and LB are owners of Unknowns Conseil en stratégie et innovation, Paris, France Disclosures of interest apart from the study Catherine Beauvais reports research grants from BMS, Fresenius Kabi, Lilly, Mylan and was an occasional speaker for BMS, Abbvie, MSD, Mylan, Pfizer, Roche, Sanofi, UCB. She participated to a medical board for Sandoz and Novartis. Thao Pham reports speaker and consulting fees from Abbvie, Amgen, Biogen, BMS, Celgene, Fresenius-Kabi, Janssen, Lilly, MSD, Nordic, Novartis, Pfizer, Sandoz, Sanofi and UCB. Florence TUBACH is head of the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique – Hôpitaux de Paris and the Clinical Research Unit of Pitié-Salpêtrière hospital; both of these structures have received unrestricted research funding and grants for the research projects handled and fees for consultant activities from a large number of pharmaceutical companies that have contributed indiscriminately to the salaries of its employees. Florence Tubach is not employed by these structures and did not receive any personal remuneration from these companies. Jérémie Sellam reports fees from MSD, Pfizer, Abbvie, Fresenius Kabi, BMS,Roche Chugai, Sandoz, Lilly, Gilead, Novartis, Janssen, grant research fromSchwa Medico, MSD and Roche.

Background: Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands associated with sicca syndrome. TAFRO syndrome is a systemic inflammatory disease of unknown cause, characterized by Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Renal dysfunction and Organomegaly, first reported in 2010 in Japanese patients. Despite their rarity, both conditions have been concurrently reported in several patients during the recent years, hence questioning the existence of shared or related features., Methods: A systematic review of the literature regarding SjS associated with TAFRO syndrome (SjS-TAFRO) was performed. The 2019 updated Masaki diagnostic criteria were used for TAFRO syndrome and SjS was considered when the diagnosis was mentioned by the authors, necessarily with either anti-Sjogren's Syndrome A (SSA) ± anti-Sjogren's Syndrome B (SSB) antibodies and/or histological evidence of focal lymphocytic sialadenitis., Results: Ten cases of SjS-TAFRO have been reported in the literature to date. Compared to SjS patients without TAFRO syndrome, these 10 SjS-TAFRO had a lower female predominance (2.3:1 vs 9:1 women to man ratio) and a higher frequency of anti-SSA antibodies (90% vs 70%). All fulfilled the three major Masaki criteria i.e., anasarca, thrombocytopenia, and systemic inflammation. Seven of them (70%) had megakaryocyte hyperplasia or reticulin fibrosis in the bone marrow. Lymph node biopsy was performed in 8 out of 10 cases (80%) and results were consistent with Castleman disease in 6 (75%). Eight of them had developed renal failure (80%) within six months. Nine of them (90%) had organomegaly, with hepatosplenomegaly in 8 cases and splenomegaly alone in 1., Conclusion: This review brings new insights regarding TAFRO syndrome and suggests it could be a severe manifestation of SjS. The identification of shared abnormal signaling pathways could help in the therapeutic management of both diseases, which face an unmet therapeutic need., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bone marrow biopsies are largely used for the diagnosis and prognostic of various hematological diseases. Complications are rare but can be as serious as hemorrhage. However, little is known about management of patients deemed at high hemorrhagic risk like thrombocytopenic patients or patients receiving antithrombotic drugs. The aim of the study was to describe the management of patients regarding their laboratory profile and antithrombotic treatment prior to bone marrow biopsy and the short-term outcomes, notably hemorrhage. We conducted a retrospective observational study between February 2007 and March 2018. A standardized form was used to collect data from patients' records, blood tests results, management of antiplatelet and anticoagulant treatment before biopsy and complications including bleeding and thromboembolic events until 3 months after the biopsy. A total of 524 bone marrow biopsies were performed. No major bleeding events were reported. The incidence of clinically relevant non-major bleeding was 0.19% (CI 95% 0.00-1.20) and was linked to low platelets counts (p = 0.002) and not to abnormal coagulation profile or antithrombotic therapy, whether or not a bridging therapy has been used. Anticoagulants were temporarily stopped before biopsy in most cases without subsequent thrombotic complications. Our data suggest that thrombocytopenic patients have a non-negligible bleeding risk. Coagulation profiling seems irrelevant. We propose an algorithm to assist the management of those patients, notably when receiving antithrombotic drugs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bradyrhizobium japonicum strain SEMIA 5079 (= CPAC 15) is a nitrogen-fixing symbiont of soybean broadly used in commercial inoculants in Brazil. Its genome has about 50% of hypothetical (HP) protein-coding genes, many in the symbiosis island, raising questions about their putative role on the biological nitrogen fixation (BNF) process. This study aimed to infer functional roles to 15 HP genes localized in the symbiosis island of SEMIA 5079, and to analyze their expression in the presence of a nod-gene inducer., Results: A workflow of bioinformatics tools/databases was established and allowed the functional annotation of the HP genes. Most were enzymes, including transferases in the biosynthetic pathways of cobalamin, amino acids and secondary metabolites that may help in saprophytic ability and stress tolerance, and hydrolases, that may be important for competitiveness, plant infection, and stress tolerance. Putative roles for other enzymes and transporters identified are discussed. Some HP proteins were specific to the genus Bradyrhizobium, others to specific host legumes, and the analysis of orthologues helped to predict roles in BNF., Conclusions: All 15 HP genes were induced by genistein and high induction was confirmed in five of them, suggesting major roles in the BNF process., (© 2022. The Author(s).)

Competing Interests: L. Grange déclare des interventions ponctuelles pour Sublimed1, Thuasne1, Remedee1 Labs, MSD, GSK, BMS, Genevrier, AbbVie, Pfizer, Roche Chugai, Roche, Lilly, Expanscience, Novartis, Amgen, AG2R, Becton Dickinson, Sanofi, Janssen, UCB, Mylan, Roche Diagnostics, Arrow, Theramex, Galapagos et avoir été pris en charge à l’occasion de déplacements pour congrès, par Lilly, AbbVie, MSD, BMS.

Objectives: This study aimed to quantify the relative importance of barriers to better secondary prevention of osteoporotic fractures and of care expectations expressed by patients with osteoporotic fractures in France., Methods: A qualitative exploration of potential barriers to care and expectations was undertaken through a systematic literature review and in-depth patients interviews. A list of 21 barriers and 21 expectations was identified. These were presented to 324 subjects with osteoporotic fractures, identified in a representative sample of the French population, in the form of best-worst scaling questionnaires. Patients rated the relative importance of the attributes, and arithmetic mean importance scores were calculated and ranked. A Bayesian hierarchical model was also performed to generate a relative importance score. Latent class analysis was performed to identify potential subgroups of patients with different response profiles., Results: A total of 7 barriers were rated as the most important, relating to awareness of osteoporosis and coordination of care. The highest-ranked barrier, "my fracture is not related to osteoporosis," was significantly more important than all the others (mean importance score 0.45; 95% confidence interval 0.33-0.56). A similar ranking of attributes was obtained with both the arithmetic and the Bayesian approach. For expectations, no clear hierarchy of attributes was identified. Latent class analysis discriminated 3 classes of respondents with significant differences in response profiles (the educated environmentalists, the unaware, and the victims of the system)., Conclusions: Better quality of care of osteoporosis and effective secondary fracture prevention will require improvements in patient education, training of healthcare professionals, and coordination of care., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Systemic autoimmune and inflammatory diseases have a complex and only partially known pathophysiology with various abnormalities involving all the components of the immune system. Among these components, antibodies, and especially autoantibodies are key elements contributing to autoimmunity. The interaction of antibody fragment crystallisable (Fc) and several distinct receptors, namely Fc receptors (FcRs), have gained much attention during the recent years, with possible major therapeutic perspectives for the future. The aim of this review is to comprehensively describe the known roles for FcRs (activating and inhibitory FcγRs, neonatal FcR [FcRn], FcαRI, FcεRs, Ro52/tripartite motif containing 21 [Ro52/TRIM21], FcδR, and the novel Fc receptor-like [FcRL] family) in systemic autoimmune and inflammatory disorders, namely rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, Crohn's disease, ulcerative colitis, immunoglobulin (Ig) A vasculitis, Behçet's disease, Kawasaki disease, IgG4-related disease, immune thrombocytopenia, autoimmune hemolytic anemia, antiphospholipid syndrome and heparin-induced thrombocytopenia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: L. Grange déclare avoir été pris en charge à l’occasion de déplacements pour congrès, par Lilly AbbVie, MSD, BMS et participer à des interventions ponctuelles pour : Sublimed1, Thuasne1, Remedee1 Labs, MSD, GSK, BMS, Genevrier, Abbvie, Pfizer, Roche Chugai, Roche, Lilly, Expanscience, Novartis, Amgen, AG2R, Becton Dickinson, Sanofi, Janssen, UCB, Mylan, Roche diagnostics, Arrow, Theramex, Arrow, Galapagos. 1Essais cliniques F. Alliot-Launois déclare n’avoir aucun lien d’intérêts.

The adenovirus 12 early region 1B55K (Ad12E1B55K) protein has long been known to cause non-random damage to chromosomes 1 and 17 in human cells. These sites, referred to as Ad12 modification sites, have marked similarities to classic fragile sites. In the present report we have investigated the effects of Ad12E1B55K on the cellular DNA damage response and on DNA replication, considering our increased understanding of the pathways involved. We have compared human skin fibroblasts expressing Ad12E1B55K (55K + HSF), but no other viral proteins, with the parental cells. Appreciable chromosomal damage was observed in 55K + HSFs compared to parental cells. Similarly, an increased number of micronuclei was observed in 55K + HSFs, both in cycling cells and after DNA damage. We compared DNA replication in the two cell populations; 55K + HSFs showed increased fork stalling and a decrease in fork speed. When replication stress was introduced with hydroxyurea the percentage of stalled forks and replication speeds were broadly similar, but efficiency of fork restart was significantly reduced in 55K + HSFs. After DNA damage, appreciably more foci were formed in 55K + HSFs up to 48 h post treatment. In addition, phosphorylation of ATM substrates was greater in Ad12E1B55K-expressing cells following DNA damage. Following DNA damage, 55K + HSFs showed an inability to arrest in cell cycle, probably due to the association of Ad12E1B55K with p53. To confirm that Ad12E1B55K was targeting components of the double-strand break repair pathways, co-immunoprecipitation experiments were performed which showed an association of the viral protein with ATM, MRE11, NBS1, DNA-PK, BLM, TOPBP1 and p53, as well as with components of the replisome, MCM3, MCM7, ORC1, DNA polymerase δ, TICRR and cdc45, which may account for some of the observed effects on DNA replication. We conclude that Ad12E1B55K impacts the cellular DNA damage response pathways and the replisome at multiple points through protein-protein interactions, causing genomic instability.

Climate-related disturbance regimes are changing rapidly with profound consequences for ecosystems. Disturbance is often perceived as detrimental to biodiversity; however, the literature is divided on how they influence each other. Disturbance events in nature are diverse, occurring across numerous interacting trophic levels and multiple spatial and temporal scales, leading to divergence between empirical and theoretical studies. The shallow Antarctic seafloor has one of the largest disturbance gradients on earth, due to iceberg scouring. Scour rates are changing rapidly along the Western Antarctic Peninsula because of climate change and with further changes predicted, the Antarctic benthos will likely undergo dramatic shifts in diversity. We investigated benthic macro and megafaunal richness across 10-100 m depth range, much of which, 40-100 m, has rarely been sampled. Macro and megafauna species richness peaked at 50-60 m depth, a depth dominated by a diverse range of sessile suspension feeders, with an intermediate level of iceberg disturbance. Our results show that a broad range of disturbance values are required to detect the predicted peak in biodiversity that is consistent with the Intermediate Disturbance Hypothesis, suggesting ice scour is key to maintaining high biodiversity in Antarctica's shallows., (© 2021. The Author(s).)

Aim: To assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases (RMDs)., Methods: REUMAVID is a cross-sectional study using an online survey developed by an international multidisciplinary patient-led collaboration across seven European countries targeting unselected patients with RMDs. Healthcare access, daily activities, disease activity and function, well-being (WHO Five Well-Being Index (WHO-5)), health status, anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and access to information were evaluated. Data were collected in April-July 2020 (first phase)., Results: Data from the first phase included 1800 patients with 15 different RMDs (37.2% axial spondyloarthritis, 29.2% rheumatoid arthritis, 17.2% osteoarthritis and others). Mean age was 53, 80% female and 49% had undertaken university studies. During the beginning of the pandemic, 58.4% had their rheumatology appointment cancelled and 45.6% reported not having received any information relating to the possible impact of SARS-CoV-2 infection in their RMDs, with the main source being patient organisations (27.6%).Regarding habits, 24.6% increased smoking, 18.2% raised their alcohol consumption, and 45.6% were unable to continue exercising. Self-reported disease activity was high (5.3±2.7) and 75.6% reported elevated pain. Half the patients (49.0%) reported poor well-being (WHO-5) and 46.6% that their health had changed for the worse during lockdown. According to HADS, 57.3% were at risk of anxiety and 45.9% of depression., Conclusion: Throughout the first wave of the COVID-19 pandemic, patients with RMDs have experienced disruption in access to healthcare services, poor lifestyle habits and negative effects on their overall health, well-being and mental health. Furthermore, information on COVID-19 has not reached patients appropriately., Competing Interests: Competing interests: HM-O reports grant/research support from: Janssen and Novartis, consultant for: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB, speakers’ bureau: AbbVie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB. HM-O is supportedby the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre.LC is an employee of Novartis Pharma AG. CJ has received grant funding from Abbvie, Amgen, Biogen, Eli Lilly, Gilead, Janssen, Pfizer, Roche, Sanofi and UCB. DW has received grant funding from AbbVie, Biogen, Janssen, Lilly, Novartis and UCB. SI has received funding from the Coronavirus Community Support Fund, distributed by The National Lottery Community Fund. SM reports unrelated honoraria from Novartis, GSK and Bayer. EF-M has received support for specific activities: grants and non-financial from Pfizer, grants from Lilly Portugal, Sanofi, AbbVie, Novartis, Grünenthal. SA., MSD, Celgene, Medac, Janssen-Cilag, Pharmakern and GAfPA, and non-financial support from Grünenthal GmbH. VN-C reports honoraria/research support from: Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Covid-19 pandemic has caused havoc in the world, radically changing our lives and raising new and old questions, both existential and educational. This pandemic has revealed the underbelly of South African society in general and its education system more specifically-it has laid bare the gross inequalities that are the legacies of apartheid and the consequences of neoliberal capitalism. Drawing on ideas articulated in the four introductory chapters of the International Handbook of Curriculum Research , edited by William Pinar in 2014, this article discusses Covid-19 and the prospects of education in South Africa. The article shows how understanding the wisdom of indigenous traditions along with the moral dimensions of education, race, and the new technologies of surveillance, neoliberalism, and education can provide a nuanced awareness of the nature of the Covid-19 pandemic. It then explores the implications of such insights for the field of curriculum studies and, where relevant, for the school curriculum. It concludes by showing how these broad themes intersect and gel around the notion of Ubuntu-currere., (© UNESCO IBE 2020.)

Objectives: To establish recommendations for pharmacological treatment of knee osteoarthritis specific to France., Methods: On behalf of the French Society of Rheumatology (SFR), a bibliography group analyzed the literature on the efficacy and safety of each pharmacological treatment for knee osteoarthritis. This group joined a multidisciplinary working group to draw up recommendations. Strength of recommendation and quality of evidence level were assigned to each recommendation. A review committee gave its level of agreement., Results: Five general principles were established: 1) need to combine pharmacological and non-pharmacological treatments, 2) personalization of treatment, 3) symptomatic and/or functional aim of pharmacological treatments, 4) need to regularly re-assess the treatments and 5) discussion about arthroplasty if medical treatment fails. Six recommendations involved oral treatments: 1) paracetamol should not necessarily be prescribed systematically and/or continuously, 2) NSAIDs, possibly as first-line, 3) weak opioids, 4) strong opioids, 5) symptomatic slow-acting drugs of osteoarthritis, and 6) duloxetine (off-label use). Two recommendations involved topical agents (NSAIDs and capsaicin<1%). Three recommendations involved intra-articular treatments: corticosteroid or hyaluronic acid injections that can be proposed to patients. The experts did not draw a conclusion about the benefits of platelet-rich plasma injections., Conclusion: These are the first recommendations of the SFR on the pharmacological treatment of knee osteoarthritis., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To describe the care trajectories of adults aged ≥50 years with fragility fractures in France., Methods: A postal questionnaire was sent to 15,000 individuals aged ≥50 years extracted from a representative panel of the French population (METASKOPE) in April-May 2018. Respondents experiencing a single fragility fracture in the previous three years constituted the study population. Information was collected regarding diagnosis, hospitalisations, physician visits and treatment related to the fractures., Results: 13,914 participants returned a questionnaire (92.8%), of whom 436 reported a single fragility fracture. Their mean age was 68.7±10.3 years. 11.9% of this sample had undergone bone densitometry (DXA) prior to the fracture and 11.9% had received a diagnostic of osteoporosis. Following the fracture, a further 17.4% underwent DXA and 8.5% were diagnosed with osteoporosis. 74.3% of fractures were initially managed in an emergency department and 29.6% led to immediate hospitalisation. Prior to fracture, 3.4% received a specific anti-osteoporotic treatment, 10.1% vitamin D and 6.4% calcium supplementation. After the fracture, these figures rose to 10.8%, 26.8% and 19.0% respectively. 86.2% participants made at least one follow-up visit to a physician., Conclusions: The rate of DXA screening following fragility fractures in subjects over fifty is very low. Most patients with fragility fractures did not receive a diagnosis of osteoporosis. The proportion of patients treated with a specific anti-osteoporotic treatment after a fracture is low even though around half consulted their general practitioner after the fracture. Practice guidelines are thus not being adhered to in everyday clinical practice in France., (Copyright © 2020. Published by Elsevier Masson SAS.)

Abdominal aneurysm is a common pathology that affects mainly men and for which there are many risk factors. This pathology predominantly stays asymptomatic until rupture and symptoms depend on location. We report the case of a 71-year-old patient. She is presenting herself to the emergency room for a nagging pain, typical of a left cruralgia as she is both febrile and shivering. The abdominal scanner is showing a ruptured infra renal aortic aneurysm. The patient is transferred to universities for an uncomplicated stent. Despite a cruralgia that seemed quite banal, both clinical and anamnestic arguments suggested an abdominal aortic rupture., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Pain in rheumatic diseases is primarily due to mechanical or inflammatory mechanism, but neuropathic pain (NP) component is also occurring in many conditions and is probably underdiagnosed. The purpose of this article is to provide an overview of prevalence, pathophysiological and currently available treatment of NP in rheumatic diseases. When associated with clinical evaluation assessing neurological clinical signs and neuroanatomical distribution, Douleur Neuropathique 4 Questions, painDETECT, Leeds assessment of neuropathic symptoms and signs and Neuropathic Pain Questionnaire can detect NP component. Inflammatory or connective diseases, osteoarthritis, back pain or persistent pain after surgery are aetiologies that all may have a neuropathic component. Unlike nociceptive pain, NP does not respond to usual analgesics such as paracetamol and non-steroidal anti-inflammatory drugs. Entrapment neuropathy, peripheral neuropathy or small-fibre neuropathy are different aetiologies that can lead to NP. A part of the pain labelled neuropathic is rather nociplastic, secondary to a central sensitisation mechanism. Identifying the right component of pain (nociceptive vs neuropathic or nociplastic) could help to better manage pain in rheumatic diseases with pharmacological and non-pharmacological treatments., Competing Interests: Competing interests: FB reports personal fees from Grünenthal, during the conduct of the study; personal fees from Lilly, Boston and Novartis, outside the submitted work; AC reports personal fees from Grunhental, outside the submitted work; PB reports personal fees from Grünenthal, during the conduct of the study; SP reports personal fees from Grünenthal, grants and personal fees from Sanofi and Pfizer, during the conduct of the study; TT reports personal fees from Grünenthal, during the conduct of the study; grants and personal fees from Amgen, Chugai, UCB, Pfizer, MSD and Novartis, personal fees from Gilead, Arrow, Biogen, BMS, Expanscience, Gilead, LCA, Lilly, Medac, Nordic, Sandoz, Sanofi, Theramex, Thuasne and TEVA, grants from Bone Therapeutics, outside the submitted work; TL reports personal fees from Grunenthal, Allergan, IPSEN and MERZ, outside the submitted work; LG reports personal fees from Grünenthal, during the conduct of the study; DW reports personal fees from Grünenthal, during the conduct of the study, personal fees from AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Celgene, Hospira, Lilly and Sandoz, outside the submitted work, indirect interests: AbbVie, Pfizer, Roche Chugai, MSD, UCB, Mylan, Fresenius Kabi. CD reports personal fees from Grünenthal, during the conduct of the study; A-PT reports personal fees from Menarini, personal fees from Recordati, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since December 2019, the COVID-19 pandemic has become a major public health problem. To date, there is no evidence of a higher incidence of COVID in patients with autoimmune rheumatic diseases and we support the approach of maintaining chronic rheumatological treatments. However, once infected there is a small but significant increased risk of mortality. Among the different treatments, NSAIDs are associated with higher rates of complications, but data for other drugs are conflicting or incomplete. The use of certain drugs for autoimmune inflammatory rheumatisms appears to be a potentially interesting options for the treatment. The rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines (Il1, IL6, TNFα) in severe forms of the disease. Notably, patients on chloroquine or hydroxychloroquine as a treatment for their autoimmune rheumatic disease are not protected from COVID-19., (Copyright © 2020 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)