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Abstract Background The genome of measles virus consists of a non-segmented single-stranded RNA molecule of negative polarity, which is encapsidated by the viral nucleoprotein (N) within a helical nucleocapsid. The N protein possesses an intrinsically disordered C-terminal domain (aa 401–525, NTAIL) that is exposed at the surface of the viral nucleopcapsid. Thanks to its flexible nature, NTAIL interacts with several viral and cellular partners. Among these latter, the Interferon Regulator Factor 3 (IRF-3) has been reported to interact with N, with the interaction having been mapped to the regulatory domain of IRF-3 and to NTAIL. This interaction was described to lead to the phosphorylation-dependent activation of IRF-3, and to the ensuing activation of the pro-immune cytokine RANTES gene. Results After confirming the reciprocal ability of IRF-3 and N to be co-immunoprecipitated in 293T cells, we thoroughly investigated the NTAIL-IRF-3 interaction using a recombinant, monomeric form of the regulatory domain of IRF-3. Using a large panel of spectroscopic approaches, including circular dichroism, fluorescence spectroscopy, nuclear magnetic resonance and electron paramagnetic resonance spectroscopy, we failed to detect any direct interaction between IRF-3 and either full-length N or NTAIL under conditions where these latter interact with the C-terminal X domain of the viral phosphoprotein. Furthermore, such interaction was neither detected in E. coli nor in a yeast two hybrid assay. Conclusion Altogether, these data support the requirement for a specific cellular environment, such as that provided by 293T human cells, for the NTAIL-IRF-3 interaction to occur. This dependence from a specific cellular context likely reflects the requirement for a human or mammalian cellular co-factor.

Purpose: Genital lymphedema is a chronic debilitating condition associated with highly impaired health-related quality of life (QoL). This prospective multicenter study evaluated the use of a new compressive garment in patients with secondary and primary genital lymphedema. Methods: Thirty-two patients prospectively enrolled were advised to wear the compressive garment for 12 weeks (day and night). The primary endpoint was change in patient-reported QoL at 12 weeks via the patient global impression of change (PGI-C) instrument. Secondary outcomes included change in other QoL measures at 12 weeks (visual analog scale, Lymphedema Quality of Life Inventory [LyQLI], and EQ-5D questionnaires), lymphedema severity (genital lymphedema score [GLS]), and physician assessment (Clinical Global Impression-Improvement [CGI-I]). Safety and tolerability were also assessed. Results: After 12 weeks, improvement was reported in 78.6% of patients (PGI-C). Physician assessment (CGI-I) indicated clinical improvement in 82.8% of patients. Patient assessment of lymphedema symptoms showed a significant decrease in discomfort ( p  = 0.02) and swelling ( p  = 0.01). Significant declines in the mean global GLS ( p  < 0.0001), and in the proportion of patients reporting heaviness, tightness, swelling, or urinary dysfunction ( p  < 0.05 for all), were also observed. LyQLI scores decreased (indicating improved QoL) in each of the physical, psychosocial ( p  = 0.05), and practical domains. The compressive garment was well tolerated with high compliance, and adverse events (due to swelling or discomfort) led to permanent discontinuation in only three patients. Conclusion: The use of a new genital compression garment over 12 weeks improves the QoL and clinical measures in patients with genital lymphedema (ClinicalTrials.gov ID: NCT04602559; Registration: October 20, 2020).

Background: Breast cancer-related lymphedema (BCRL) after primary therapy is a common condition, causing physical and psychological distress. Decongestive lymphedema therapy (DLT) using multi-layered compression bandages is an effective treatment. We conducted a randomized controlled trial evaluating the use of a specific mobilizing bandage (Mobiderm ® ) on lymphedema volume reduction during the intensive phase of DLT. Methods and Results: Fifty female BCRL patients were randomized to receive either conventional multi-layered bandages or mobilizing bandaging by using Mobiderm. Affected limb volume and excess volume were evaluated at baseline (D0) and after 15 days. The primary outcome was change in affected limb volume after adjustment for baseline. Symptom scores were evaluated by visual analogue scale (VAS); safety and tolerability were also assessed. Baseline characteristics were comparable. Affected limb volume reduction was observed in both study groups after 15 days: by 19.0% in the Mobiderm arm and 8.6% in controls (adjusted values). The between-group mean difference in adjusted volume reduction at day 15 was 256 mL (95% confidence interval [CI], 92.5 to 421.3 mL; p  = 0.003) favoring Mobiderm. Reductions in excess volume of 57.3% (Mobiderm) and 25.1% (controls) were observed (adjusted values); with between-group mean difference in adjusted excess volume of 220.2 mL (95% CI, 69.3 to 371.3 mL; p  = 0.006) favoring Mobiderm. Pain/heaviness VAS scores fell significantly in both groups, with mean reductions of 1.84 (Mobiderm) versus 0.83 (control; p  = 0.001). Both regimens were well tolerated. Conclusion: The use of Mobiderm in multilayer compression bandaging shows benefit in lymphedema reduction and in alleviating functional symptoms/pain in patients with BRCL.

Background: Home hospitalization at the end of life can sometimes be perturbed by unplanned hospital admissions (UHAs, defined as any admission that is not part of a preplanned care procedure), which increase the likelihood of death in hospital. The objectives were to describe the occurrence and causes of UHAs in cancer patients receiving end-of-life care at home, and to identify factors associated with UHAs and death in hospital., Methods: A retrospective, single-center study (performed at a regional cancer center in the city of Lille, northern France) of advanced cancer patients discharged to home hospitalization between January 2014 and December 2017. We estimated the incidence of UHA over time using Kaplan-Meier method and Kalbfleish and Prentice method. We investigated factors associated with the risk UHA in cause-specific Cox models. We evaluated factors associated with death in hospital in logistic regressions., Results: One hundred and forty-two patients were included in the study. Eighty-two patients (57.7 %) experienced one or more UHAs, a high proportion of which occurred within 1 month after discharge to home. Most UHAs were related to physical symptoms and were initiated by the patient's family physician. A post-discharge palliative care consultation was associated with a significantly lower incidence of UHAs. Sixty-five patients (47.8 % of the deaths) died in hospital. In a multivariate analysis, living alone and the presence of one or more children at home were associated with death in hospital., Conclusions: More than 40 % of cancer patients receiving end of life home hospitalization were not readmitted to hospital, reflecting the effectiveness of this type of palliative care setting. However, over half of the UHAs were due to an acute intercurrent event. Our results suggest that more efforts should be focused on anticipating these events at home - primarily via better upstream coordination between hospital physicians and family physicians.

Objective: Since February 2016, French Claeys-Leonetti law has recognized patients' right to confront incurable diseases with short-term prognosis and refractory physical or psychological or existential symptoms by requesting continuous deep sedation until death (CDSUD). Determining when psychological or existential distress is refractory and unbearable remains complex and controversial.This review provides a comprehensive thought on CDSUD for advanced incurable patients with refractory psychological and/or existential distress in palliative care settings. It offers guidance on psychiatric or psychological diagnosis for explaining patients' requests for CDSUD., Method: A narrative literature review (2000-2019) was conducted on the MedLine search about the use of palliative sedation in cases of refractory psychological and/or existential distress., Results: (1) Definitions of "refractory symptom," "refractory psychological distress," and "refractory existential distress" are inconsistent; (2) alternative diagnoses might obscure or be obscured by psycho-existential distress; and (3) criteria on meanings, reasons for requests, decision-making processes, and functions are evolving in practice., Significance of Results: Before implementing CDSUD, palliative healthcare professionals should seek input from psycho-oncologists in palliative care. Mental health professionals should analyze and assess the reasons for psychological and/or existential distress, consider the intentionality processes of requests, and explore alternative diagnoses, such as depressive or adjustment disorders, demoralization syndrome, desire to hasten death, and desire for euthanasia. Therapeutic responses (e.g., pharmacological and psychotherapeutic) should be implemented before deciding that psycho-existential distress is refractory.

Background: French legislation about sedation in palliative medicine evolved in 2016 with the introduction of a right to deep and continuous sedation, maintained until death. The objective was to describe midazolam sedation at the COL (Centre Oscar Lambret [Oscar Lambret Center], French regional center for cancer control), in order to establish a current overview before the final legislative changes., Methods: Descriptive, retrospective and single-center study, concerning major patients in palliative care hospitalized from 01/01/2014 to 12/31/2015, who had been sedated by midazolam. The proven sedations (explicitly named) and the probable sedations were distinguished., Results: A total of 54 sedations were identified (48 proven, 6 probable). Refractory symptoms accounted for 48.1% of indications, complications with immediate risk of death 46.3%, existential suffering 5.6%. Titration was performed in 44.4% of cases. Sedation was continuous until death for 98.1% of the cases. Probable sedation had a higher failure rate than proven sedation. Significant differences existed for the palliative care unit compared to other units regarding information to the patient, their consent, anticipation, mention by correspondence and carrying out titrations. When patients had already been treated with midazolam, the induction doses, initial maintenance doses, and doses at the time of death were significantly higher. For those receiving opioids, the maintenance dose at the time of death was higher. No comparison found a difference in overall survival., Conclusions: After a sufficient follow-up has enabled teams to familiarize with this new legislation, reflection on sedation should be conducted to adapt to final recommendations.

Purpose: The identification and referral of patients in need of palliative care should be improved. The French society for palliative support and care recommended to use the PALLIA-10 questionnaire and its score greater than 3 to refer patients to palliative care. We explored the use of the PALLIA-10 questionnaire and its related score in a population of advanced cancer patients., Methods: This prospective multicentric study is to be conducted in authorized French comprehensive cancer centers on hospitalized patients on a given day. We aimed to use the PALLIA-10 score to determine the proportion of palliative patients with a score >3. Main secondary endpoints were to determine the proportion of patients already managed by palliative care teams at the study date or referred to palliative care in six following months, the prevalence of patients with a score greater than 5, and the overall survival using the predefined thresholds of 3 and 5., Results: In 2015, eighteen French cancer centers enrolled 840 patients, including 687 (82%) palliative patients. 479 (69.5%) patients had a score >3, 230 (33.5%) had a score >5, 216 (31.4%) patients were already followed-up by a palliative care team, 152 patients were finally referred to PC in the six subsequent months. The PALLIA-10 score appeared as a reliable predictive (adjusted OR R ef≤3 : 1.9 [1.17-3.16] and 3.59 [2.18-5.91]) and prognostic (adjusted HR R ef≤3  = 1.58 [95%CI 1.20-2.08] and 2.18 [95%CI 1.63-2.92]) factor for patients scored 4-5 and >5, respectively., Conclusion: The PALLIA-10 questionnaire is an easy-to-use tool to refer cancer inpatients to palliative care in current practice. However a score greater than 5 using the PALLIA-10 questionnaire would be more appropriate for advanced cancer patients hospitalized in comprehensive cancer center., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Over-the-counter medicines may be proposed by pharmacists for children with acute cough. Study objectives were to describe the sociodemographic profile of children who were proposed a cough syrup by a pharmacist, the nature of the cough and type(s) of cough syrup proposed and to assess the evolution of the cough, tolerance and satisfaction with treatment., Methods: Observational, prospective, longitudinal, multicentre study with 157 pharmacies in France. Children who were proposed a cough syrup by a pharmacist were recruited. Questionnaires were completed by the pharmacists and/or parents at inclusion and by the parents after 5 days of treatment., Results: Four hundred fourteen children were included (mean age: 6.0±2.9 years); 45.9% had a dry and 43.3% a productive cough. 30.4% were proposed an allopathic antitussive syrup, 28.3% an allopathic expectorant syrup and 23.7% a homeopathic syrup. Children with a dry cough were more likely to be given an allopathic antitussive (55.2%) or homeopathic (28.2%) syrup. Children with a productive cough or cough of several days duration were more likely to be given an allopathic expectorant syrup (70.1%). Cough disappearance was more frequent with homeopathic syrups compared to allopathic expectorants (P=0.002), or allopathic antitussives (P=0.042). Adverse events were most common with allopathic antitussive syrups (18.7%) (P<0.001). Two-thirds of parents were satisfied with the treatment their child received., Conclusions: Pharmacists play an important role in the management of acute cough in children. Homeopathic cough syrups may have an interest in terms of public health.

Background: Anxiety and sleep disorders (SDS) are frequently treated with psychotropic drugs. Health authorities in France have been advised to improve access to alternative treatments such as homeopathic medicines. Our aim was to describe the socio-demographic characteristics and clinical progression of patients prescribed homeopathic medicine Passiflora Compose (PC) for anxiety and/or SDS., Material and Methods: This was an open-label, observational study. Randomly selected general practitioners (GPs) known to prescribe homeopathic medicines recruited consecutive patients (≥18-years) prescribed PC. The following data were recorded at inclusion by the GP: socio-demographic data and anxiety severity (Hamilton anxiety rating scale or HAM-A); and by the patients: level of anxiety (STAI Spielberger self-assessment questionnaire) and SDS (Jenkins sleep scale or JSS). Anxiety and SDS were reassessed after 4 weeks of treatment using the same scales., Results: A total of 639 patients (mean age: 46.3 ± 17.5 years; 78.6% female) were recruited by 98 GPs. Anxiety was present in 85.4% (HAM-A) and 93.3% (Spielberger State) at inclusion (mean scores: 17.8 ± 8.91 and 54.59 ± 11.69, respectively) and SDS was present in 74.0% (mean score: 15.24 ± 5.28). A total of 401 (62.7%) patients received PC alone and 167 (26.1%) PC + psychotropics. After 4 weeks, mean anxiety scores decreased by more than 7, 12 and 6 points (HAM-A, Spielberger State and Trait respectively), and SDS score by more than 4 points (JSS)., Conclusion: Anxiety and/or SDS improved significantly in patients included on this study. PC could be an alternative to the use of psychotropic drugs for first intention treatment of anxiety and SDS. Further studies are needed to confirm those results., (Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.)

Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Aim: Physical or psychological well-being is an essential component of quality care assessment in palliative unit. This assessment is mainly based on self-assessment (questionnaires or interviews). The aim of this study is to compare the clinical characteristics of patients able to fulfill a questionnaire and those not able to do that., Methods: The clinical characteristics of 166 cancer patients admitted in palliative care unit from December 2006 to February 2008 have been collected. Characteristics of patients able to fulfill a questionnaire (80, 48.2%) have been compared to other patients (86, 51.8%). Moreover, functional independence measure (FIM) had been evaluated by nurses., Results: Median age (60 versus 62) and sex ratio (40/40 versus 42/44) are similar in both groups. Lung primaries are significantly less frequent in patients able to fulfill the questionnaire (4% versus 17%, P=0.005). Patients able to fulfill the questionnaire had had better performance status (Karnofsky Index≤30%: 54% versus 21%, P<0.0001). The total score of FIM (56.0 versus 91.5, P<0.00001) and the median overall survivals (2.3 weeks versus 6.6 weeks, P=0.0001) were significantly lower in the group of patients non able to fulfill the questionnaire., Conclusions: Patients able to fulfill a questionnaire represent only 48.2% of all consecutive admitted patients. These patients are not representative of all patients since they had better performance status, they are less dependent and they display significant better survival. We have to think about new methods to avoid the biases generated by the use of patient-reported outcomes., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The modest impact of specific treatments is a major problem in oncology and particularly for metastatic lung cancer patients. Therapeutic progress achieved by some targeted therapies is, in fact, only relevant for a small proportion of patients. The vast majority of people with this condition are rapidly confronted by the limits of specific therapies and management is or becomes entirely palliative. This article addresses therapeutic limitations in the management of metastatic lung cancer, as well as legislative aspects and guidelines for practitioners when discussing these issues with patients, together with a discussion of the psychological consequences for patients., (Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.)