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Contact dermatitis from frullania mainly affects people living in the country. The 2 most frequent species in Europe, Frullania dilatata and Frullania tamarisci, do not cross-react: both species must be patch tested when frullania intolerance is suspected. Yet patch testing with frullania may be hazardous: 9 out of 37 cases recorded in Strasbourg correspond to active sensitization by the tests. Since routine testing is risky, only aimed testing can be recommended. [ABSTRACT FROM AUTHOR]

Background: A lack of medication adherence among patients with rheumatoid arthritis (RA) has been reported. Inter-professional collaborations seem essential for an optimal therapeutic management of patients. The aim of this study was to analyse the barriers and facilitators of general practitioners (GPs) for the implementation of collaborative support programmes in RA., Methods: A qualitative semi-structured study using face-to-face or telephone interviews was conducted. Eligible participants included French GPs referring patients with RA. Interviews were audio-recorded and then transcribed. Data were analysed using Braun and Clarke's thematic analysis framework with Nvivo ® 12 software., Results: Nineteen GPs were interviewed between August 2019 and February 2020. Five themes were identified in the care of their patients with RA. GPs reported being mainly involved in diagnosis and orientation, and frequently asked for pain management and explanation/reformulation of previously given information. They perceived their patients to be adherent to their treatments, although they frequently identified reasons for non-adherence. Regarding their perception of the community-hospital relationship, they sometimes considered it insufficient and expected more immediate interactions. Additionally, most interviewed GPs had no expectation regarding increased collaborations with community pharmacists (CPs) and several GPs were motivated to be more involved in a patient support programme. However, barriers were identified: lack of time and training, and insufficient payment., Conclusions: The implementation of a collaborative patient support programme in RA should be developed taking into account the barriers and facilitators identified by GPs who appeared to be aware of the causes of potential non-adherence, and were particularly interested in receiving more information about the therapeutic monitoring of patients by hospital professionals., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was obtained from the ethics committee of the Université Claude Bernard Lyon 1 (No. IRB: 2019-05-21-03) on the 21th May 2019. Informed consent was obtained from the participants prior to study participation. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication: All participants provided written consent for publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Current clinical trials indicate that repetitive transcranial magnetic stimulation (rTMS) is effective in reducing drug-resistant neuropathic pain (NP). However, there is a lack of studies evaluating the long-term feasibility and clinical efficacy of rTMS in large patient cohorts in real-world conditions., Methods: In this retrospective cohort study, we analysed 12 years of clinical data to assess the long-term analgesic effects of 20 Hz rTMS over the primary motor cortex in patients with NP. Subgroup analyses were conducted to identify predictive factors and assess the potential role of epidural motor cortex stimulation (eMCS) as a sustained solution., Results: In total, 193 patients completed test period of 4 rTMS sessions and 42% of them reported a pain relief (PR) greater than 30%, with concurrent improvement in their most disabling symptom. Iterative rTMS sessions maintained analgesic effects over 10 years in certain patients identified as responders (≥10% PR) without adverse effects. Success probability was higher in patients with central NP compared to peripheral NP (OR = 2.03[1.04;4.00]), and among those with central post-stroke pain, this probability was higher in ischemic versus hemorrhagic strokes (OR = 3.36[1.17;10.05]). PR obtained with iterative rTMS sessions was an excellent predictor of eMCS efficacy., Conclusions: While rTMS shows promise as a therapeutic option for some patients with drug-resistant NP, it does not benefit all patients. Efficacy varies by NP aetiology, aiding patient selection. For responders, eMCS may offer a permanent solution. These findings support a tailored approach to rTMS in NP management, while recognizing both its potential and limitations across diverse patient profiles., Significance Statement: Multiple rTMS sessions demonstrate long-term efficacy and safety in treating drug-resistant neuropathic pain. Extending session numbers for the test period can enhance responder identification, especially in patients with initial low pain relief. This identification refines patient selection for neurosurgery, reducing non-responders. Central neuropathic pain shows higher success rates than peripheral. For post-stroke central pain, patients with ischemic stroke are more likely to respond than those with hemorrhagic stroke. These results support integrating rTMS into clinical practice for managing neuropathic pain., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Objectives: We aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months., Patients and Methods: French patients were prospectively recruited in two centers in 2015-2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files., Results: Previous antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20-2.21], 1.59 [1.02-2.48], 3.01 [1.90-4.77], and 2.60 [1.75-3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41-1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18])., Conclusions: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery., (Copyright © 2024. Published by Elsevier Masson SAS.)

Introduction: In France, 40% of patients diagnosed with lung cancer are ≥70 years old, but these are under-represented in clinical trials. Using data from the French Epidemiological Strategy and Medical Economics (ESME) platform on Lung Cancer (LC), the objective is to provide an overview of the management and the prognosis of older patients with advanced or metastatic non-small cell lung cancer (AM-NSCLC) in a real-world context., Materials and Methods: From the ESME-LC database, we selected patients with AM-NSCLC (stage IIIB, IIIC, and IV), diagnosed between 2015 and 2019, and who received first-line systemic treatment. Demographics, tumour characteristics, and treatment received were described in patients ≥70, and compared to younger ones. Real-world progression-free survival (rwPFS) and overall survival (OS) were evaluated using the multivariable Cox model., Results: Among 10,002 patients with AM-NSCLC, the median age was 64 years, with 2,754 (27.5%) aged ≥70. In comparison with patients <70, older patients were more often male, with worse performance status and more comorbidities, but they were less underweight and more often non-smokers. The proportion of EGFR mutated non-squamous NSCLC was higher in older patients (25.0% vs 12.8%, p < 0.001), particularly among smokers and former smokers (12.7% vs 7.3%, p < 0.001). Among patients ≥70, 76.6% received first-line chemotherapy (including 67.0% treated with a platinum-based doublet), 15.0% received only targeted therapy, and 11.0% received immunotherapy (alone or in combination). Median first-line rwPFS was 5.1 months (95% confidence interval [CI] = [4.8;5.4]) for patients ≥70 and 4.6 months (95%CI = [4.4;4.8]) for patients <70, but age was not associated with rwPFS in multivariable analysis. Median OS was 14.8 months (95%CI = [13.9;16.1]) for patients ≥70 and 16.7 months (95%CI = [15.9;17.5]) for patients <70, with a significant effect of age in multivariable analysis for patients treated with chemotherapy and/or with targeted therapy, but not for patients treated with immunotherapy (alone or in combination with chemotherapy)., Discussion: In this real-world cohort of patients with AM-NSCLC, age was not associated with first-line rwPFS regardless of treatment received, nor with OS for patients receiving immunotherapy. However, OS was significantly shorter for patients aged ≥70 treated with chemotherapy or with targeted therapy alone., Competing Interests: Declaration of Competing Interest Mathilde Cabart reports non-financial support from Janssen, non-financial support from Pfizer, outside the submitted work. Loïc Mourey reports personal fees and non-financial support from Sanofi, personal fees from Astellas, personal fees and non-financial support from Janssen, personal fees and non-financial support from MSD, personal fees and non-financial support from BMS, personal fees and non-financial support from Ipsen, personal fees and non-financial support from Astra-Zeneca, personal fees and non-financial support from Pfizer, personal fees from Merck, outside the submitted work. David Pasquier has nothing to disclose. Sophie Schneider has nothing to disclose. Hervé Léna reports personal fees and non-financial support from Roche, personal fees from Astrazeneca, personal fees and non-financial support from MSD, personal fees and non-financial support from Novartis, personal fees and non-financial support from Takeda, personal fees from BMS, personal fees and non-financial support from Pfizer, non-financial support from Lilly, personal fees and non-financial support from Amgen, outside the submitted work. Nicolas Girard reports grants and personal fees from AstraZeneca, personal fees from Daiichi, grants and personal fees from Roche, grants and personal fees from MSD, grants and personal fees from BMS, grants and personal fees from Pfizer, grants and personal fees from Janssen, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Takeda, grants and personal fees from Novartis, grants and personal fees from Sanofi, outside the submitted work; and Family Member employee of AstraZeneca. Christos Chouaid reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, grants, personal fees and non-financial support from GSK, grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Sanofi Aventis, grants, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Lilly, grants, personal fees and non-financial support from Novartis, grants, personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from Takeda, grants, personal fees and non-financial support from Bayer, grants, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from Viatris, grants, personal fees and non-financial support from Chugai, grants, personal fees and non-financial support from Pierre Fabre, grants, personal fees and non-financial support from Amgen, outside the submitted work. Roland Schott reports personal fees and non-financial support from Roche, non-financial support from Takeda, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Pfizer, non-financial support from IPSEN, personal fees and non-financial support from BMS, outside the submitted work. Sandrine Hiret reports non-financial support from Roche, non-financial support from Novartis, other from Sanofi, other from Astra Zeneca, other from Takeda, other from BMS, outside the submitted work. Didier Debieuvre has nothing to disclose. Xavier Quantin has nothing to disclose. Anne Madroszyk has nothing to disclose. Pascale Dubray-Longeras reports personal fees from MSD, personal fees from AstraZeneca, personal fees and non-financial support from Takeda, non-financial support from Pfizer, outside the submitted work. Eric Pichon reports personal fees and non-financial support from Takeda, personal fees from AstraZeneca, personal fees from MSD, outside the submitted work. Anne Baranzelli has nothing to disclose. Grégoire Justeau has nothing to disclose. Maurice Pérol reports personal fees and non-financial support from Takeda, personal fees from Janssen, personal fees and non-financial support from AstraZeneca, outside the submitted work. Lise Bosquet has nothing to disclose. Bastien Cabarrou has nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Influenza vaccines are effective in decreasing hospitalizations and mortality related to influenza and its complications. However, the Vaccine Coverage Rate of influenza remains low and multifaceted efforts are required to improve it. The aim of this study was to assess the impact on influenza vaccine perception using a digital tool among outpatients and health care workers (HCWs)., Methods: A study was performed among outpatients and the HCWs of 23 hospital departments from 4 hospitals affiliated to Lyon university Hospitals (France), between October 2022 and February 2023. By scanning QR (Quick Response) codes, displayed on posters for patients, their companions, as well as in the letters sent to HCWs, users accessed anonymously to a web-application (ELEFIGHT®), which provided information on influenza and invited them to initiate a discussion on influenza prevention with their physicians during the consultation. Patients were also invited to complete a questionnaire regarding their perception of influenza vaccination before and after reading the information on ELEFIGHT®. The retention rate (RR = proportion of people who remain on the page for >2 s), the conversion rate (CR = proportion of people who click on the "Call-To-Action" button) and the absolute variation (difference in the perception before/after) and relative variation (absolute change as a percentage of the initial perception) in perception regarding influenza vaccination before and after consulting the application were calculated., Results: 3791 scans were performed by 3298 patients and/or their companions with a RR of 52% and a CR of 55.1% and 253 scans by 221 HCWs with a RR of 71.2% and a CR of 115.3%. Participants spent an average of 47 s on the application. The questionnaire on influenza vaccination perception was completed by 1533 participants (46.5%); 1390 (90.7%) maintained the same position (neutral, favorable or unfavorable) on this vaccination before and after consulting the application. The relative variations in favor of vaccination were + 7.2% (unfavorable then favorable) and + 19.8% (neutral then favorable)., Conclusion: This study suggests that a facilitated direct access to medical information through QR codes disseminated in health settings can help nudge people to foster their awareness of influenza and its prevention. Future deployments in a similar context or to other populations could be envisaged. Other vaccine-preventable and/or chronic diseases could also be the target of similar projects as part of public health programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nagham Khanafer, Florence Ader, Frédéric Berard, Françoise Bouhour, Roland Chapurlat, Sybil Charriere, Cyrille Confavreux, Gilles Devouassoux, Emmanuel Disse, Jean-Pierre Fauvel, Denis Fouque, Herve Ghesquieres, Sophie Hyvert, Anne Jolivot, Gilles Leboucher, Catherine Lombard, Géraldine Martin-Gaujard, Jean-Francois Mornex, Marc Nicolino, Nathalie Obadia, Gérald Raverot, Philippe Reix, Alain Ruffion, Pascal Seve, Eric Truy, Fabien Zoulim and Philippe Vanhems have no conflicts of interest related to this study to declare. Catherine Planckaert, Rym Bouhalila, Camille Mena and Nadège Trehet Mandel have been mandated and paid by the HCL. Sylvain Oudot, Margot Maligeay, Joséphine Clamens and Marie-Pierre Ayala are employed by Sanofi., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools., Methods: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist., Results: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002)., Conclusions: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Document Reviewers: Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception., Methods: The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis., Results: PT decreased between 3 periods, from 1.1% in 2000-2005 (58/5123) to 0.7% in 2006-2010 (30/4600) and to 0.2% in 2011-2017 (10/4907; P < .001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000-2005 to 0.03% (1/3117) in 2011-2017 (P = .007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011-2017 period., Conclusions: In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero., Competing Interests: Potential conflicts of interest. C. D. reports support for attending meetings and/or travel from ViiV Healthcare for conference on retroviruses and opportunistic infections registration fees. P. F. reports grants or contracts and participation on a data and safety monitoring board or advisory board from ANRS-MIE; consulting fees from MSD France and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and support for attending meetings and/or travel from MSD France, Gilead Sciences, ViiV Healthcare, Bristol Myers Squibb, and Janssen Cilag. J. G. reports grants or contracts from ViiV Healthcare and Gilead Sciences (paid to institution) and consulting fees from ViiV Healthcare, Gilead, MSD France, Astra Zeneca, Theratechnologies, and Janssen (paid to author). J. W. reports an academic grant from INSERM-ANRS and support for attending meetings and/or travel from INSERM-ANRS (academic grant). V. A.-F. reports grants or contracts from ANRS, MSD Avenir Foundation, and ViiV Healthcare (paid to institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead and ViiV Healthcare (paid to author); and support for attending meeting and/or travel from ViiV Healthcare (paid to author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To assess whether antiretroviral therapy (ART) prescriptions differ between naive and virally suppressed HIV patients born in France (PBFs) and in Sub-Saharan Africa (PBSSAs)., Setting: Observational single-center study., Methods: We included all PBFs and PBSSAs who entered into care at Pitié-Salpêtrière Hospital, Paris, France, from 01/01/2000 to 31/12/2018, with plasma HIV-RNA>200 copies/mL. We first compared the initial ART in naive PBFs and PBSSAs. Second, we compared the last-prescribed ART (including drug-reduced ART: daily 2-drug regimens, daily 1-drug regimens and intermittent 3-drug regimens) in virally suppressed PBFs and PBSSAs, by focusing on patients in care in 2018 with HIV-RNA <50 copies for at least 24 months. A univariable and multivariable logistic regression model was used to assess the impact of geographical origin on ART prescriptions., Results: A total of 1944 naive patients were included (915 PBSSAs and 1029 PBFs). PBSSAs were more frequently women, hepatitis B coinfected, with a lower pretherapeutic CD4 T-cell count, and most had tuberculosis at HIV diagnosis. After adjustment for confounders, PBSSAs were more likely to receive a first-line protease inhibitor-based regimen (OR 1.61, 95% CI: 1.31 to 1.98), and less likely to receive an integrase inhibitor-based regimen (OR 0.61, 95% CI: 0.42 to 0.88). Of the 968 virally suppressed patients (431 PBSSAs and 537 PBFs), PBSSAs were less likely to receive drug-reduced ART, including 2-drug regimens and intermittent three-drug regimens (OR 0.48, 95% CI: 0.36 to 0.65)., Conclusions: Differences in ART prescriptions between PBSSAs and PBFs were not only explained by different clinical and virologic situations. Personal motivations of doctors in choosing ART according to country of birth need to be explored., Competing Interests: R.P., L.C., S.S., C.S., R.T., M.A.V., L.S., V.P., and C.K. have received travel grants and honoraria from Gilead, ViiV Healthcare, and Merck. AGM has received travel and research grants and honoraria from Gilead, ViiV Healthcare, Theratechnologies and Merck. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The Institute of Pharmacology of the University of Strasbourg played an eminent role in the development and international spread of pharmacology between 1872 and 1918. In this article, genealogy and biographies of key players are documented. Unfortunately, lack of data did not permit the complete biographical description of all scientists. Oswald Schmiedeberg played a decisive role in the global establishment of pharmacology, having trained most of the professors of his time. From Strasbourg, pharmacology spread into many countries including Germany, Austria, Switzerland, Italy, Norway, the UK, and the USA. The Institute of Pharmacology in Strasbourg played a major role in the establishment of both academic pharmacology and the modern pharmaceutical industry. The Institute of Pharmacology in Strasbourg also mirrors the history of Germany and France and the Nazi period., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage diseases caused by defective enzyme activity involved in the catalysis of glycosaminoglycans. Published data on adult patients with MPS remains scarce. Therefore, the present qualitative survey study was aimed at understanding knowledge of the disease, unmet needs, expectations, care, and overall medical management of adult/adolescent patients with MPS I, II and VI and their caregivers in France., Results: A total of 25 patients (MPS I, n p  = 11; MPS II, n p  = 9; MPS VI, n p  = 5) were included and about 36 in-depth interviews (caregivers alone, n c  = 8; patients-caregiver pair, n c+p  = 22; patients alone, n p  = 6) were conducted. Except one (aged 17 years), all patients were adults (median age: 29 years [17-50]) and diagnosed at median age of 4 years [0.4-30], with mainly mothers as caregivers (n c  = 16/19). Patients were classified into three groups: Group A, Patients not able to answer the survey question because of a severe cognitive impairment (n p  = 8); Group B, Patients able to answer the survey question with low or no cognitive impairment and high motor disability (n p  = 10); and Group C, Patients able to answer the survey question with low or no cognitive impairment and low motor disability (n p  = 7). All groups were assessed for impact of disease on their daily lives based on a scale of 0-10. Caregivers in Group A were found to be most negatively affected by the disease, except for professional activity, which was most significantly impacted in Group B (4.7 vs. 5.4). The use of orthopaedic/medical equipments, was more prevalent in Groups A and B, versus Group C. Pain management was one of the global unmet need expressed by all groups. Group A caregivers expected better support from childcare facilities, disability clinics, and smooth transition from paediatric care to adult medicine. Similarly, Group B caregivers expected better specialised schools, whereas Group C caregivers expected better psychological support and greater flexibility in weekly infusion schedules for their patients., Conclusions: The survey concluded that more attention must be paid to the psychosocial status of patients and caregivers. The preference for reference centre for follow-up and treatment, hospitalizations and surgeries were evident. The most significant needs expressed by the patients and caregivers include better understanding of the disease, pain management, monitoring of complications, flexibility in enzyme replacement therapy, home infusions especially for attenuated patients, and improved transitional support from paediatric to adult medicine., (© 2022. The Author(s).)

Regarding animal experiments in pharmacology teaching, ethical considerations led us to examine an alternative approach to the use of living animals. This study aimed to assess whether digital tools could replace live animal experiments in terms of motivation and knowledge acquisition. The study was carried out with students enrolled in the 5th year of the industry/research stream at the Faculty of Pharmacy of the University of Limoges. The participants were randomly assigned to groups of traditional or digital teaching methods, with the common theme of the class being the effect of a diuretic agent (furosemide) in rats. The scenario and learning objectives were identical for the two groups. Before the class and after randomization, the acceptance of the digital educational material was assessed with a scale, which predicts the acceptability of users according to individual dimensions and social representations, followed by the assessment of the motivation by a situational motivation scale (SIMS) for both groups. After the class, the students' motivation was assessed by a questionnaire based on Deci and Ryan's self-determination theory. In the end, the participants were evaluated for homogeneity, based on general knowledge of renal pharmacology, and for knowledge acquisition concerning specific knowledge related to this teaching session. This study revealed a good acceptance of the digital tool and a good motivation toward the digital method among all the students. It found the two teaching methods (digital and traditional) to be equivalent in terms of motivation and knowledge acquisition. In our study, digital pedagogical tools as an alternative to live animals did not affect students' motivation and knowledge acquisition., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Context: High fracture risk in individuals with low muscle strength is attributed to high risk of falls., Objective: This work aims to study the association of muscle mass and physical performance with bone microarchitecture decline and risk of fall and nonvertebral fracture in men., Methods: A prospective, 8-year follow-up of a cohort was conducted among the general population. A total of 821 volunteer men aged 60 and older participated. Hip areal bone mineral density (aBMD) and appendicular lean mass (ALM) were assessed at baseline by dual x-ray absorptiometry. Lower-limb relative ALM (RALM-LL) is ALM-LL/(leg length)2. The physical performance score reflects the ability to perform chair stands and static and dynamic balance. Bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and after 4 and 8 years. Statistical analyses were adjusted for shared risk factors. Outcome measurements included the rate of change in the HR-pQCT indices, incident falls, and fractures., Results: Cortical bone loss and estimated bone strength decline were faster in men with low vs normal RALM-LL (failure load: -0.74 ± 0.09 vs -0.43 ± 0.10%/year; P < .005). Differences were similar between men with poor and those with normal physical performance (failure load: -1.12 ± 0.09 vs -0.40 ± 0.05%/year; P < .001). Differences were similar between men having poor performance and low RALM-LL and men having normal RALM-LL and performance (failure load: -1.40 ± 0.17 vs -0.47 ± 0.03%/year; P < .001). Men with poor physical performance had a higher risk of fall (hazard ratio [HR] = 3.52; 95% CI, 1.57-7.90, P < .05) and fracture (HR = 2.68; 95% CI, 1.08-6.66, P < .05)., Conclusion: Rapid decline of bone microarchitecture and estimated strength in men with poor physical performance and low RALM-LL may contribute to higher fracture risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT)., Methods: Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221-C-001 trial and SoC outcomes obtained from a real-world chart review of patients in France., Results: Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61-1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47-0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72-13.24) and 4.76 months for SoC (95% CI, 3.81-8.21). Results remained robust across all sensitivity analyses conducted., Conclusions: PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The present study aimed to compare the precarious migrants' health problems managed in Médecins du Monde's health and social care centres (CASO) with those of patients attending general practice in France. Methods: We compared the most frequent health problems managed in the 19 CASO in metropolitan France with those of a national sample of usual general practice consultations, after standardisation for age and sex. Results: Precarious migrants had fewer health problems managed per consultation than other patients (mean: 1.31 vs. 2.16), and these corresponded less frequently to chronic conditions (21.3% vs. 46.8%). The overrepresented health problems among CASO consultations were mainly headache (1.11% vs. 0.45%), viral hepatitis (1.05% vs. 0.20%), type 1 diabetes (1.01% vs. 0.50%) and teeth/gum disease (1.01% vs. 0.23%). Their underrepresented health problems were mainly lipid disorder (0.39% vs. 8.20%), depressive disorder (1.36% vs. 5.28%) and hypothyroidism (0.50% vs. 3.08%). Prevention issues were nominal in precarious migrants (0.16%). Conclusion: Both chronic somatic and mental conditions of precarious migrants are presumably underdiagnosed. Their screening should be improved in primary care., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Halley, Giai, Chappuis, Tomasino, Henaine and Letrilliart.)

Organic matter has an important role in biogeochemistry in aquatic environments. This study investigated impact of suspended particulate organic matter (SPOM) on fluorescence signal of mixtures of three water types (river water RW, sea water SW, effluent wastewater WW) using fluorescence (excitation-emission matrix, EEM) spectroscopy and parallel factor analysis (PARAFAC) and multilinear regression. Four irradiation experiments (Expt-1, Expt-2, Expt-3, and Expt-4) were conducted during different times of the year ( two in autumn, one in winter, and one in spring season). Samples were exposed to natural sunlight on laboratory rooftop in University of Toulon, France, with another set of samples kept in dark as control samples. Three component (C1, C2, C3) model was validated by split-half and Concordia from the whole EEM dataset of all irradiation experiments. No protein-like fluorophores was found. The study revealed the effect of SPOM presence/absence on fluorescence signal of DOM and on resulting parameters of multilinear regression MLR model and kinetic constant of these MLR parameters. Kinetic constant (k) for all MLR coefficients was in order of greatness as Expt-1 (SPOM of WW only in mixtures) > Expt-3 (SPOM of SW only in mixtures) > Expt-2 (SPOM of RW only in mixtures)> Expt-4 (SPOM of RW + SW + WW in mixtures) indicating that SPOM of WW is the most resistant to photodegradation. For dark control samples, only relative standard deviation RSD could be calculated from dataset. RSD values for C3 were the highest indicating its chaotic variations, and the lowest RSD values were found for both C1 and C2 for all experiments. Statistical differences has been found between control and irradiated experiments. These models developed in this study can be used to predict fluorescence signal of anthropogenic effluent DOM during its transport in river systems to coastal zone., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

[Figure: see text].

Background: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer., Methods: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m 2 from day 1 to day 3]) or oral topotecan (2·3 mg/m 2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02738346., Findings: Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0-37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9-5·5 vs 2·7 months, 2·3-3·2; stratified hazard ratio 0·57, 90% CI 0·41-0·73; p=0·0041). The most frequent grade 3-4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group., Interpretation: Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer., Funding: Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The monitoring of bioaerosol concentrations in the air is a relevant endeavor due to potential health risks associated with exposure to such particles and in the understanding of their role in climate. In this context, the atmospheric concentrations of bacteria were measured from January 2018 to May 2020 at Saclay, France. The aim of the study was to understand the seasonality, the daily variability, and to identify the geographical origin of airborne bacteria. Methods: 880 samples were collected daily on polycarbonate filters, extracted with purified water, and analyzed using the cultivable method and flow cytometry. A source receptor model was used to identify the origin of bacteria. Results: A tri-modal seasonality was identified with the highest concentrations early in spring and over the summer season with the lowest during the winter season. Extreme changes occurred daily due to rapid changes in meteorological conditions and shifts from clean air masses to polluted ones. Conclusion : Our work points toward bacterial concentrations originating from specific seasonal-geographical ecosystems. During pollution events, bacteria appear to rise from dense urban areas or are transported long distances from their sources. This key finding should drive future actions to better control the dispersion of potential pathogens in the air, like persistent microorganisms originating from contaminated areas.

The aim of the study was to evaluate the acceptability and to describe the perception of vaccination against herpes zoster (HZ) for outpatients and hospitalized patients in Lyon, France, aged 65 years and over. An observational study was based on a questionnaire completed from a face-to-face interview from January 2018 to March 2019. Volunteer outpatients who attended private medical laboratories or who were hospitalized in the geriatric department, or who were at the ambulatory medical clinic for a consultation were asked to participate. A total of 907 individuals were interviewed, with a mean age of 75.8 years. A large majority 87.6% (795) knew about HZ and 68.9% (625) would agree to be vaccinated against HZ if they had risk factors. The participants had knowledge of HZ as a disease but vaccine awareness is still lacking among the general public., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Karst systems, as well as springs, are vulnerable to water perturbation brought by infiltration. In this research, sources of water perturbations were examined. The first objective is to provide a method that can determine the origin of the water flowing in the karst outlet. The second objective is to identify the associated water quality hazards caused by the infiltration source. The method relies on these parameters: turbidity, DOC, NO 3 - , particle size, and bacteria (E. coli, enterococcus and total coliforms). As the method was applied during flood events, measurement of the water flow is also needed to have a basic knowledge on the hydrodynamic of the water resource. The proposed method is based on a high resolution monitoring of physico chemical parameters of the water flowing during flood events. Using this proposed method, (1) the origin of the water can be identified, (2) the type and nature of water perturbation can be described, and (3) the type of water perturbation that accompanies contaminants such as the one with anthropogenic source (e.g. NO 3 - ) and bacterial nature can be determined. In identifying the water origin, this proposed method employed NO 3 - and DOC data normalization. Values are projected in the NO 3 ), and presence or absence of bacteria were examined. This method was applied in the springs of the Toulon, an important drinking water source of the city of Périgueux in France. This site was chosen considering the following factors: (1) its karst nature being vulnerable to infiltrations, having fractures and sinkholes; (2) its land use being influenced by the anthropogenic activities such as agriculture; and (3) its observed pronounced turbidity incidence. The first flood events of two hydrological cycles were assessed. Three water origins of the spring water and the respective water quality hazards were identified: (i) water from saturated zone with minerals, (ii) water from unsaturated zone with nitrate, and (iii) water from surface runoff with the presence of bacteria. The second and third types of water perturbation gave evidence that the Toulon springs can be contaminated. Hence, in terms of resource management, the information obtained can be used as a basis in forecasting and planning the management actions or water quality treatments needed.- &#95;norm = f(DOC&#95;norm) reference frame. These are aligned to the slope. Depending on the obtained slope (α), water origin can be disclosed. If α > 1, the increase of concentration of DOC weighs more, characterizing water from surface runoff. Whereas, if α < 1, the consideration is more on the increase of NO 3 - concentration, characterizing water from unsaturated zone. However if α cannot be calculated because there is no evident slope, this characterizes the water already present in the system. Water originating from the surface runoff is prone to inorganic and bacterial contamination adsorbed by the particles. Identifying the type of water perturbation needing water treatment is important in managing the water resource. Hence, the evolution through time of NO 3 - and DOC with the particle size distribution, anthropogenic nature type of contaminant (i.e. in this study NO 3 - ), and presence or absence of bacteria were examined. This method was applied in the springs of the Toulon, an important drinking water source of the city of Périgueux in France. This site was chosen considering the following factors: (1) its karst nature being vulnerable to infiltrations, having fractures and sinkholes; (2) its land use being influenced by the anthropogenic activities such as agriculture; and (3) its observed pronounced turbidity incidence. The first flood events of two hydrological cycles were assessed. Three water origins of the spring water and the respective water quality hazards were identified: (i) water from saturated zone with minerals, (ii) water from unsaturated zone with nitrate, and (iii) water from surface runoff with the presence of bacteria. The second and third types of water perturbation gave evidence that the Toulon springs can be contaminated. Hence, in terms of resource management, the information obtained can be used as a basis in forecasting and planning the management actions or water quality treatments needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Several studies documented declines in treatment adherence with generic forms of oral bisphosphonates in osteoporosis compared to branded forms, while others did not support this relation. Our aim was to compare medication adherence with brand versus generic forms of oral bisphosphonates. A new-user cohort study was conducted using routinely collected administrative and healthcare data linked at the individual level extracted from a nationwide representative sample of the French National Healthcare Insurance database. We included all patients aged 50 and older, new users of oral bisphosphonates for primary osteoporosis between 01/01/2009 and 31/12/2015. Two components of adherence were measured: implementation (continuous multiple-interval measure of medication availability version 7; CMA7) and persistence (time to discontinuation). The sample was composed of 1,834 in the "brand bisphosphonate" group and 1,495 patients in the "generic bisphosphonate" group. Initiating oral bisphosphonate treatment with brand was associated with a higher risk of discontinuation within 12 months (Hazard Ratio = 1.08; 95%CI = [1.02;1.14]). The risk of good implementation (CMA7 ≥ 0.90) was significantly lower in "brand bisphosphonate" group (Risk Ratio = 0.90; 95%CI = [0.85; 0.95]). We did not find any evidence to support the hypothesis of a lower adherence to generic bisphosphonates. In fact, prescribing of generic bisphosphonates led to a higher persistence rate and to better implementation at 1 year.

Abri Pataud (France) is the type site in studies focusing on the appearance of modern humans and the development of classic Upper Paleolithic technocomplexes in Europe. It contains important evidence of successful adaptation strategies of modern humans to new territories and in response to sharply changing climatic conditions that characterized Marine Isotope Stages 3 and 2. Despite being for decades one of the best excavated and most studied Paleolithic sites, the chronology of Abri Pataud has lacked precision and revealed large discrepancies. The chronology of the lowermost part of the sequence (Levels 14-5) was refined in 2011 with the publication of 32 new radiocarbon determinations, mainly from the Aurignacian levels. In contrast, the Gravettian levels (Levels 5-2) remained poorly dated until now. Here, we present 18 new radiocarbon dates on cut-marked animal bones from the Gravettian part of the site, which complete the dating of this important sequence. The determinations are analyzed using Bayesian statistical modeling, and the results allow us to place the start of the Gravettian at the site between ∼33,000 and 32,000 cal BP (∼29,000-28,000 BP). We discuss the succession of the Gravettian facies across the sequence (Bayacian, Noaillian, Rayssian), as well as the likely duration of each archaeological level. With a total of more than 50 radiocarbon determinations, Abri Pataud offers secure information for the appearance and development of the technocomplexes linked with early modern humans and their establishment in western Europe. Based on published genetic data, it appears that it is the Gravettian hunter-gatherers and subsequent human groups, rather than the earlier Aurignacian and pre-Aurignacian groups, that contributed to the genetic signature of later and living Europeans. Hence, elucidating the precise timing of the Gravettian appearance has broad implications in our understanding of late human evolution across Europe., Competing Interests: Conflict of interest The authors disclose no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Osteoporosis (OP) is responsible for an important economic burden, but OP care is far from meeting therapeutic guidelines. Some interventions were effective to improve OP management. Our objective was to evaluate the cost-effectiveness of these interventions. Structural interventions and interventions consisting in sending educational material were dominant strategies., Purpose: Osteoporosis (OP) causes many osteoporotic fractures worldwide and an important economic burden as a result. OP care is far from meeting treatment guidelines, but in a recent meta-analysis, we showed that some interventions were effective to improve appropriate bone mineral density (BMD) and treatment prescriptions. In the context of limited resources, it is of major importance to measure these interventions' efficiency. Our objective was to evaluate the cost-effectiveness of existing effective intervention types., Methods: We used a decision tree incorporating Markov models to compare costs and benefits (quality-adjusted life-years or QALYs) between usual care and three intervention types: structural (I), direct educational through conversation (II), and indirect educational by sending material (III). We adopted the collectivity perspective and chose a 30-year time horizon. The model included efficacy of interventions and risk of further fracture or death, depending on BMD T-score results and OP management, obtained from published literature. The model was populated to reflect a French setting. Deterministic and probabilistic sensitivity analyses were conducted. Costs were presented in 2018 euros (€)., Results: Interventions type I and III were dominant strategies compared with usual care (cost-saving with a QALY gain). Our results were consistent through sensitivity analyses., Conclusion: Our results suggest that structural interventions and indirect interventions to improve OP care (BMD and OP treatment prescription), in women 50 years old with a first fragility fracture, were dominant strategies.

Background: Herbicides inhibiting the synthesis of very long-chain fatty acids (HRAC group K 3 , WSSA group 15), such as flufenacet, play an important role in weed management strategies, particularly when herbicide resistance to inhibitors with other modes of action, such as acetolactate synthase or acetyl coenzyme A carboxylase (ACCase), has already evolved. So far, only a few cases of resistance towards inhibitors of the synthesis of very long-chain fatty acids have been described. In this study, we characterized the level of flufenacet resistance in several Lolium spp. field populations and investigated the resistance mechanism., Results: The screening for flufenacet resistance revealed the ability of Lolium spp. populations from several continents to survive flufenacet treatments at and above the field rate. This study demonstrates the way in which flufenacet is detoxified in resistant weed populations. Glutathione was found to be conjugated to flufenacet in Lolium spp. seedlings, and there was evidence that glutathione transferase activity was enhanced in protein extracts from flufenacet-resistant seedlings. A significant correlation was found between the resistance factor obtained by biotests and the degradation half-time of flufenacet in ryegrass plants obtained by high-performance liquid chromatography (HPLC)., Conclusion: At present, flufenacet resistance is not widespread; however, in certain Lolium spp. populations resistance levels could reach agronomic relevance due to detoxification by glutathione transferases. In Europe especially, only a few herbicide modes of action are registered for the control of Lolium spp. and therefore it is becoming increasingly important to apply best management practices to prevent the spread of flufenacet resistance. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Purpose: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles., Methods: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included., Results: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04)., Conclusion: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

The aim of this study is to assess the species status of the Middle-European Thanasimus Latreille, 1806 species using mitochondrial CO1 sequence data. Molecular biological results clearly support the synonymy of T. pectoralis (Fuss, 1863) and T. rufipes (Brahm, 1797) with T. femoralis (Zetterstedt, 1828) as already proposed by Kolibáč (1992). Results of the present study indicate high genetic variation within T. formicarius (Linné, 1758) and emphasize the study of population dynamics of T. formicarius within Europe. Furthermore, preliminary screening of all available T. formicarius sequences on BOLD and Genbank (shorter than 500bp) indicates the presence of a "Continental" and a more "Atlantic" clade in T. formicarius. To support our hypothesis of a probably cryptic species among T. formicarius, more studies, with more specimens from different populations, especially from southern England, northern France and the northern part of the Iberian Peninsula, will be necessary.

North Africa is one of the rare regions where the HIV epidemic is growing. In France, 5% of the migrants discovering their HIV infection are from North Africa. The objective of this study was to compare the sociodemographic characteristics and outcomes of North African and French HIV-infected patients. This study was conducted in the HIV clinic of Bichat Hospital (Paris, France). The North African HIV-infected patients were born in Algeria, Tunisia, or Morocco or had lived there for more than 6 months. They were matched for age and gender (1:2) to patients born in France who had never lived outside France for more than 6 months. Sociodemographic, clinical, and immunovirological characteristics of North African and French patients were compared using conditional logistic regression. Among 4,738 eligible patients, 285 North Africans were identified. CD4 levels at HIV diagnosis were not significantly different between North African and French patients, but were more frequently <200/mm 3 in the former than the latter at treatment initiation ( p  = .02). CDC stage 3 disease occurred more frequently in the first 3 years of care in our center in North African patients than in French patients ( p  = .01), and control of the HIV viral load over the 12 months preceding inclusion was better in French patients ( p  = .0001). There was no difference regarding loss to care. These results highlight possible issues in adherence to antiretroviral treatment in North African patients, which may be related to differences in the acceptability of the disease.

Influenza D virus (IDV) has first been identified in 2011 in the USA and was shown to mainly circulate in cattle. While IDV is associated with mild respiratory signs, its prevalence is still unknown. In the present study we show that IDV has been circulating throughout France in cattle and small ruminants, with 47.2% and 1.5% seropositivity, respectively. The high prevalence and moderate pathogenicity of IDV in cattle suggest that it may play an initiating role in the bovine respiratory disease complex.

Background: Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis., Methods: Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality., Results: Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (Δ H24-H0 ) show good prediction of mortality. These results suggest that NMR-based metabolomic analysis is useful for a better overall assessment of septic shock patients., Conclusions: Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes., Trial Registration: All human serum samples were collected and stored, provided by the "center of biologic resources for liver disease", in Jean Verdier Hospital, Bondy, France (BB-0033-00027).

Background: Reliable epidemiological data on Alzheimer's disease are scarce. However, these are necessary to adapt healthcare policy in terms of prevention, care and social needs related to this condition. To estimate the prevalence rate in the Alpes-Maritimes on the French Riviera, with a population of one million, we present a capture-recapture procedure applied to cases of Alzheimer's disease, based on two epidemiological surveillance systems., Methods: To estimate the total number of patients affected by Alzheimer's disease, a capture-recapture study included a cohort of patients with Alzheimer's disease or receiving medications only eligible for use for this condition, recorded by a specific health insurance information system (Health Insurance Cohort, HIC), and those registered in the French National Alzheimer's Data Bank ("Banque Nationale Alzheimer", BNA) in 2010 and 2011. We applied Bayesian estimation of the Mt ecological model, taking into account age and gender as covariates, i.e. factors of inhomogeneous catchability., Results: Overall, 5,562 patients with Alzheimer's disease were recorded, of whom only 856 were common to both information systems. Mean age and F/M sex ratio differed between BNA and HIC surveillance systems, 81 vs 84 years and 2.7 vs 3.2, respectively. A Bayesian estimation, with age and gender as covariates, yields an estimate of 15,060 cases of Alzheimer's disease [95%HPDI: 14,490-15,630] in the Alpes-Maritimes. The completeness of the HIC and BNA databases were respectively of 25.4% and 17.2%. The estimated prevalence rate among the population over 65 years old was 6.3% in 2010-2011., Conclusions: This study demonstrates that it is possible to determine the number of subjects affected by Alzheimer's disease in a geographical unit, using available data from two existing surveillance systems in France, i.e. 15,060 cases in the Alpes-Maritimes. This is the first stage of a population-based approach in view of adapting available resources to the population's needs., Competing Interests: The authors have declared that no competing interests exist.

Background: High rates of liver enzyme elevation (LEE) in women receiving antiretroviral treatment (ART) during pregnancy have been reported, but causes remain unclear. We estimated the prevalence and risk factors of LEE in a national prospective multicenter cohort., Methods: We studied 5748 pregnant women living with HIV enrolled in the French Perinatal Cohort 2005-2014, treated with ART, with no active hepatitis B or C coinfection. Adjusted hazard ratio (aHR) was estimated using Cox models with ART as time-dependent variable, separately for women on ART at conception and those initiating ART during pregnancy., Results: LEE (grade ≥ 1) was observed in 16.7%, grade 3-4 in 2%. Among women with LEE, 6.7% had pre-eclampsia, 9.8% intrahepatic cholestasis of pregnancy, and 1.4% other identified medical causes. Most LEEs (82.2%) were unexplained. In women with unexplained LEE, LEE was the reason for hospitalization in 51 (6%) women, cesarean section in 13 (2%), induction of labor in 3 (0.4%), and change in ART regimen in 49 (6%) women. Unexplained LEE was associated with higher risk of preterm births, P < 0.001. Among women on ART at conception, the risk of unexplained LEE was lower with NNRTI-based regimens than with PI-based regimens: aHR = 0.5 (0.3-0.7), with no difference among the PI drugs. Most women initiating ART during pregnancy were on a PI-based regimen (89%). Among them, LEE was less frequent for women on nelfinavir vs. lopinavir/r [aHR = 0.4 (0.2-0.8)]., Conclusions: Rates of LEE among pregnant women living with HIV are high and impact obstetrical care management. The possible role of PIs needs further investigation.

Introduction: Limited "real life" data on raltegravir (RAL) use during pregnancy are available. Thus, we aimed at describing effectiveness and safety of RAL-based combined antiretroviral therapy (cART) in this setting., Methods: HIV-1-infected women receiving RAL during pregnancy between 2008 and 2014 in ten French centers were retrospectively analysed for: (1) proportion of women receiving RAL anytime during pregnancy who achieved a plasma HIV-RNA (pVL) < 50 copies/mL at delivery, and (2) description of demographics, immuno-virological parameters and safety in women and new-borns., Results: We included 94 women (median age, 33 years) of which 85% originated from Sub-Saharan Africa and 16% did not have regular health insurance coverage. Sixteen women were cART-naïve (median HIV diagnosis at 30 weeks of gestation), whereas 78 were already on cART before pregnancy (40% with pVL < 50 copies/mL). RAL was initiated before pregnancy (n = 33), during the second trimester (n = 11) and the third trimester of pregnancy (n = 50). No RAL discontinuations due to adverse events were observed. Overall, at the time of delivery, pVL was < 50 copies/mL in 70% and < 400 copies/mL in 84% of women. Specifically, pVL at delivery was < 50 copies/mL in 82%, 55% and 56% of cases when RAL was started before pregnancy, during the second or third trimester of pregnancy, respectively. Median term was 38 weeks of gestation, no defect was reported and all new-borns were HIV non-infected at Month 6., Conclusions: RAL appears safe and effective in this "real-life" study. No defect and no HIV transmission was reported in new-borns., Competing Interests: We have the following interests: Dominique TRIAS is employed by Merck Sharp Dohme France, who also provided funding for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Objectives: With HIV treatment as a prevention strategy, retention in care remains a key for sustained viral suppression. We sought to identify HIV-infected patients at risk for medical care interruption (MCI) in a high-income country., Methods: The HIV-infected patients enrolled had to attend the clinic at least twice between January 2010 and October 2014 and were followed up until May 2016. MCI was defined as patients not seeking care in or outside the clinic for at least 18 months, regardless of whether they returned to care after the interruption. The association between MCI and sociodemographic, clinical, and immuno-virological characteristics at HIV diagnosis and during follow-up was assessed using Cox models., Results: The incidence rate of MCI was 2.5 per 100 persons-years (95% confidence interval [CI] = 2.3-2.7). MCI was more likely in patients who accessed care >6 months after diagnosis (hazard ratio [HR] = 1.30, 95% CI = 1.10-1.54 vs. ≤6 months) or did not report a primary care physician (HR = 2.40; 95% CI = 2.03-2.84). MCI was less likely in patients born in sub-Saharan Africa (HR = 0.75, 95% CI = 0.62-0.91 vs. born in France). During follow-up, the risk of MCI increased when the last CD4 count was ≤350 (HR = 2.85, 95% CI = 2.02-4.04 vs. >500 cells/mm3) and when the patient was not on antiretroviral therapy (HR = 3.67, 95% CI = 2.90-4.66)., Conclusions: The incidence of MCI is low in this hospital that serves a large proportion of migrants. Low or no recorded CD4 counts for a medical visit could alert of a higher risk of MCI, even more in patients who accessed HIV care late or did not report a primary care physician., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following updated competing interests: YY has served as a speaker and as a consultant for Abbott, Bristol-Myers Squibb, Gilead, MSD, Roche, Tibotec and ViiV Healthcare outside the present work. KC has served as a speaker and as a consultant for Gilead outside the present work. RV received travel grants from Gilead, Merck and ViiVHealthCare outside the present work. JJP reports grants from ViiV Healthcare and MSD, and personal fees from Gilead, ViiV Healthcare and MSD outside the present work. RL reports grants from ViiV Healthcare, MSD, and personal fees from Gilead, ViiV Healthcare, Janssen and MSD outside the present work. SL reports personal fees from MSD outside the present work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure., Methods: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants., Results: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries., Conclusions: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence., (© 2019 S. Karger AG, Basel.)

Background: Pharmacists contribute to reduce the number of medication errors during medication review. Nevertheless, few French studies report the potential clinical impact of pharmacists' interventions performed after detecting drug-related problems. The objective was to evaluate the clinical relevance of pharmacists' interventions in a rheumatology ward from medical and pharmaceutical perspectives., Method: The analysis was conducted on pharmacists' interventions performed between January 1 and December 31, 2015 in a French teaching hospital. Similar pharmacists' interventions were grouped in one item and they were analysed according to 11 drug categories. The clinical significance of pharmacists' interventions was considered independently by a pharmacist and a rheumatologist using a validated French scale that categorises drug-related problems from minor to catastrophic. The agreement between the two professionals was analysed using the weighted kappa coefficient., Results: Of 1313 prescriptions reviewed, 461 pharmacists' interventions (171 items) were formulated for drug-related problems with an acceptance rate of 67.2%. Of the 418 interventions selected for clinical significance analysis, 235 interventions (56.2%) for the physician and 400 interventions (95.7%) for the pharmacist were at least significant. The two professionals evaluated equally the clinical relevance of 90 items (50.6%). The categories with the most similarities were the analgesics/anti-inflammatory drugs (78.1%), the antidiabetics (75.0%) and the anticoagulants (71.4%). The agreement was estimated by a weighted kappa coefficient of 0.29., Conclusion: This work highlights the positive clinical relevance of pharmacists' interventions in rheumatology and the importance of medico-pharmaceutical collaboration to prevent medication errors., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To update the 2012 recommendations on pharmacotherapy for postmenopausal osteoporosis, under the aegis of the Bone Task Force of the French Society for Rheumatology (SFR) and of the Osteoporosis Research and Information Group (GRIO), in collaboration with scientific societies (Collège national des généralistes enseignants, Collège national des gynécologues et obstétriciens français, Fédération nationale des collèges de gynécologie médicale, Groupe d'étude de la ménopause et du vieillissement hormonal, Société française de chirurgie orthopédique, Société française d'endocrinologie, and Société française de gériatrie et de gérontologie)., Methods: Updated recommendations were developed by a task force whose members represented the medical specialties involved in the management of postmenopausal osteoporosis. The update was based on a literature review and developed using the method advocated by the French National Authority for Health (HAS)., Discussion and Conclusion: The updated recommendations place strong emphasis on the treatment of women with severe fractures, in whom the use of osteoporosis medications is recommended. All the available osteoporosis medications are suitable in patients with severe fractures; zoledronic acid deserves preference as the fist-line drug after a hip fracture. In patients with or without non-severe fractures, the decision to use osteoporosis medications is based on bone mineral density values and in challenging cases, on probabilities supplied by prediction tools such as FRAX ® . All osteoporosis medications are suitable; raloxifene should be reserved for patients at low risk for peripheral fractures. The fracture risk should be reevaluated every 2 to 3 years to decide on the best follow-up treatment. These updated recommendations discuss the selection of first-line osteoporosis medications and treatment sequences., (Copyright © 2018. Published by Elsevier Masson SAS.)

Release of heavy metals into the soil pose a significant threat to the environment and public health because of their toxicity accumulation in the food chain and persistence in nature. The potential of soil microbial diversity of cadmium (Cd) contaminated site was exploited through functional metatranscriptomics by construction of cDNA libraries A (0.1-0.5 kb), B (0.5-1.0 kb), and C (1-4 kb) of variable size, from the eukaryotic mRNA. The cDNA library B was further screened for cadmium tolerant transcripts through yeast complementation system. We are reporting one of the transformants ycf1 Δ PLBe1 capable of tolerating high concentrations of Cd (40 μM - 80 μM). Sequence analysis revealed that PLBe1 cDNA showed homology with ubiquitin domain containing protein fused with AN1 type zinc finger protein of Acanthameoba castellani. Further, this cDNA was tested for its tolerance towards other heavy metals such as copper (Cu), zinc (Zn) and cobalt (Co). Functional complementation assay of cDNA PLBe1 showed a range of tolerance towards copper (150 μM - 300 μM), zinc (10 mM - 12 mM) and cobalt (2 mM - 4 mM). This study promulgates PLBe1 as credible member of multi-metal tolerant gene in the eukaryotic soil microbial community and can be used as potential member to revitalise the heavy metal contaminated sites or can be used as a biomarker to detect heavy metal contamination in the soil environment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still, there is a lack of unbiased data to conclude on its efficacy. The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in patients with cirrhosis., Methods and Analysis: This study is a multicentre, randomised, double-blind, placebo-controlled trial, for adult patients with cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or placebo (saline). Physicians from emergency mobile services, emergency departments (EDs) or intensive care units (ICUs) can include patients. Besides study intervention, standard care for UGIB will be performed as recommended. Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or saline, immediately followed by three identical intravenous infusions over 8 hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main analyses will be conducted in intention to treat on every patient included, then in modified intention to treat on patients with underlying lesion of portal hypertension visualised by endoscopy. The main objective is to show efficacy of TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes and mortality). Secondary objectives aim at showing the efficacy of TXA on each individual component of the main outcome measure and others at 6 weeks and later (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific complications, length of stay in ICU and in hospital, safety and tolerance of TXA, liver transplantation). Included patients will be followed up to 1 year after inclusion.500 patients will be necessary to show a reduction in the prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of 5% and a power of 80%., Ethics and Dissemination: Ethical approval has been obtained from the Comité de Protection des Personnes Ile-de-France 1 (CPP-IDF1). Results will be disseminated via publications in peer-review medical journals and scientific forums., Protocol Version: This protocol is based on the latest version, as established on 11 October 2017 and validated by the IRB CPP Ile-de-France 1., Trial Registration Number: NCT03023189., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study describes the time trend of renal replacement therapy for end-stage renal disease (ESRD) in the Provence-Alpes Côte d'Azur region (PACA) between 2004 and 2015, and forecasts up to 2030., Methods: A longitudinal study was conducted on all ESRD patients treated in PACA and recorded in the French Renal Epidemiology and Information Network (REIN) during this period. Time trends and forecasts to 2030 were analyzed using Poisson regression models., Results: Since 2004, the number of new patients has steadily increased by 3.4% per year (95% CI, 2.8-3.9, p < 0.001) and the number of patients receiving RRT has increased by 3.7% per year (RR 1.037, 95% CI: 1.034-1.039, p < 0.001). If these trends continue, the PACA region will be face with 7371 patients on dialysis and 3891 with a functional renal transplant who will need to be managed in 2030. The two most significant growth rates were the percentage of obese people (RR 1.140, 95% CI: 1.131-1.149, p < 0.001) and those with diabetes (RR 1.070, 95% CI; 1.064-1.075, p < 0.001)., Conclusion: This study highlights the increase in the number of ESRD patients over 12 years, with no prospect of stabilization. These findings allow us to anticipate the quality and quantity of care offered and to propose more preventive measures to combat obesity and diabetes.

Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection., Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years., Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death., Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred., Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.

Background: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is frequent in HIV-infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART)., Methods: Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available., Results: Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6.2% (95% confidence interval: 5.4 to 6.8) and 1.7% (1.3 to 2.1), respectively. HCV coinfection was strongly associated with a history of drug use; HBV coinfection was 6 times more frequent in women born in Sub-Saharan Africa than in European France. Baseline HIV viral load, CD4 count, and HIV care during pregnancy were similar in coinfected and monoinfected HIV mothers, except that 90% of HBV/HIV women were receiving tenofovir and/or lamivudine or emtricitabine. HCV coinfection was significantly associated with cholestasis [adjusted odds ratio: 4.1 (1.5-10.8), P = 0.005], preterm delivery [3.0 (1.6-5.7), P < 0.001], lower CD4 [2.6 (1.0-6.4), P < 0.001], and detectable viral load [2.3 (1.0-5.5), P = 0.06] at the end of pregnancy. HBV coinfection was not associated with any of these outcomes., Conclusions: In HIV-infected women, chronic HBV infection, mostly treated using targeted ART, had no major impact on the course of pregnancy. By contrast, chronic HCV infection was associated with a higher risk of obstetrical complications and a poorer immune-virological response to ART. It is yet unknown whether cure of HCV infection before conception can limit these adverse outcomes.

Background/aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme., Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described., Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >-2). No new or unexpected safety concerns were noted., Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged., (© 2018 S. Karger AG, Basel.)

Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world's population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.