Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study.

Funder: This work was supported by Bristol Myers Squibb (no grant number is applicable).BACKGROUND: Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. METHODS: IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. RESULTS: Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti-programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab-treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab-treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. CONCLUSIONS: With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01511913. Registered January 19, 2012 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913

Idea original, coordinación y maquetación por Deborah González Jurado

La traducción de las canciones de Virginia Rodrigo al francés comporta, como casi todas las traducciones de obras de la cultura popular contemporánea, ricas en semánticas específicas, lenguaje común coloquial, frases hechas y giros idiomáticos, comportó ciertas dificultades que fueron solucionadas por estudiantes de máster y doctorado francófonas con conocimientos avanzados de francés. Aún así, ciertas expresiones "intraducibles", hubieron de ser explicadas de forma concreta y paratextual. Dada la amplia casuística generada a lo largo del proceso de traducción, inferimos que estos textos pueden servir como ejemplo para la praxis del estudio del español en general y de la traductología en particular, por lo que creemos puede ser de interés ponerlos a disposición de estudiantes, profesores y del público en general.El presente cuadernillo es el resultado de la idea de traducir las letras de las canciones de Virginia Rodrigo al francés, con motivo del evento de dos jornadas (Concierto —día 6 de diciembre 2021— y Conferencia musicalizada —7 de diciembre 2021—) del Seminario 'Humor y Feminismo(s)' del subequipo CHISPA del equipo AMERIBER, organizado por Deborah González Jurado en la Universidad Bordeaux-Montaigne. Al tratarse de un evento abierto a toda la comunidad universitaria, y no solo a los/las estudiantes de las licenciaturas de español, se decidió aportar al público este cuadernillo para ayudar a los no hispanoparlantes en la comprensión del humor feminista español, más un power point que se proyectó en directo en la sala donde se celebró el concierto. Todas las canciones forman parte del repertorio de Virginia Rodrigo, y en su mayoría pertenecen al disco "La Intrusa", aunque algunas podemos encontrarlas en otros de sus álbumes publicados. Casi todas son accesibles para su escucha desde la plataforma Youtube en abierto

Drug Utilization Studies in Pregnant Women for Newly Licensed Medicinal Products: A Contribution from IMI ConcePTION

Purpose. Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation. However, there is often less information for subpopulations, such as pregnant or breastfeeding women, particularly when new medicines are considered. It is important to understand what information can be obtained from drug utilization studies (DUS) involving pregnant women in the early years postmarketing to provide supportive information for safety studies. The aims of this literature review are to (1) identify and review DUS for new medicines in pregnancy and breastfeeding and (2) list and summarise key information items to be reported in a DUS for new medicines in pregnancy. Methods. To identify postmarketing DUS of new prescription medicines or enantiomers in pregnancy, a systematic literature review was undertaken in PubMed and Embase between January 2015 and June 2022. In addition, the complete database of the ENCePP EU PAS Register was systematically searched to June 2022. Results. We identified 11 published DUS on new medicines in pregnancy from the ENCePP EU PAS Register and none from other sources. No studies on breastfeeding were identified. The 11 identified publications reported the medicine’s use for the first 3 to 5 years after marketing approval. No reports assessed utilization in the first 3 years of approval. It was usual to issue interim reports annually (7 studies). All studies concerned conditions managed in ambulatory care (primary care and outpatient facilities) and included some primary care prescribing. Most (n=8) only had prescribing/dispensing data available at individual level for ambulatory care; outpatient prescribing was included in three of these studies Three studies held a limited amount of in-hospital prescribing data. A DUS can confirm at an early stage whether there are sufficient exposed pregnancies in available data sources to ensure a safety study is powered to detect a difference in the prevalence of adverse pregnancy or infant outcomes or if additional data from other databases are needed. A DUS may also help address methodological considerations such as selection of comparators. DUS can be performed embedded in a DUS in the general population, in a cohort of women of childbearing age, or in a cohort of pregnant women. Conclusion. This review summarises key aspects of a DUS for new medicines in pregnancy. DUS for new medicines in pregnancy should be planned before marketing, scheduled for the first 3 to 5 years after release, with annual interim/progress reports, and reported in peer-reviewed journals. By offering detailed information on data sources, exposure timing, prevalence and location, coprescribing, comorbidities, coexposures, and demographics, a DUS will offer a firm foundation for safety studies and will help to contextualize spontaneous reporting of serious adverse events

Coworkers, Makers and Hackers in the city : Reinventing policies, corporate strategies and citizenship ?

The world of work is changing. A century after moving from an agriculture-centered world to an Industrial one, from self-employed workers to salaried employees, our modern economies are slowly transitioning towards a new model: based on simultaneous collaboration and competition, the boundaries of contemporary organizations are blurring; information technologies are allowing individuals and companies to set base away from cities; shared working spaces are triggering new forms of collaborations between individuals and corporations.This White Paper aims at diagnosing key institutional tensions related to new work practices in the city, and putting forward questions and general propositions likely to overcome these tensions. The idea is to analyze how new collaborative communities and collaborative logics (of coworkers, hackers, makers, fabbers, and teleworkers) and more traditional collective activity and modes of decision making (of the city and corporations in the city) can jointly contribute to the co-production of harmonious new ways of life and new ways of working. Reinventing joint public policies, corporate strategies and citizenship appear here as a key stake where usual dichotomies between private-public, collaborative-non-collaborative economy, traditional citizens and hacktivists need to be overcome.We thus identify in this document a set of controversies around four strong political issues both for the city and the field of management, linked to the emergence of collaborative spaces:o Topic 1. Space, territories, and public policy on collaborative communities in the city;o Topic 2. Collaborative communities and their roles in education in the city;o Topic 3. Business models and their communication in the context of collaborative spaces and collaborative communities;o Topic 4. Collaborative spaces and their roles in innovation and entrepreneurial dynamics at the level of the cityBeyond our controversies, we underline three paradoxes which should be at the heart of new questions for policy-makers, hacktivists, actors of collaborative movements, and citizens (distinctions which may become less and less relevant in the years to come):o Social versus economic orientations of both the city and the collaborative communities it can host;o Critical/revolutionary versus more incremental relationships between cities, organizations, societies, collaborative communities, and new work practices;o Local territory (district/proximate area) grounded versus broader city-oriented or connectivity related issues about collaborative movement and new work practices.To balance these tensions, we elaborate seven general areas of questions and propositions for all stakeholders:o The generalization of infra-organization (physical collaborative platforms);o The emergence of “ ‘inclusive lab’ labels” (elaborated and managed by collaborative communities themselves);o A renewed academic presence in the city and in the country-side (with more virtual, distributed and ‘experiential’ logics);o Ephemeral and mobile labs managed jointly by public, collaborative and private stakeholders;o “Open open” innovation in public and semi-public spaces of the city;o Rise of mega-spaces for creativity in the city;o Development of a global infrastructure for coworkers, mobile workers and teleworkers.These are directions we see as particularly promising to manage the tensions, paradoxes and stakes explicated by our controversies.We hope that these questions and propositions will inspire both academics, politicians, hacktivists and entrepreneurs for future collaborations on the study and joint transformation of public policies, corporate strategies, and citizenship

Coworkers, Makers and Hackers in the city : Reinventing policies, corporate strategies and citizenship ?

The world of work is changing. A century after moving from an agriculture-centered world to an Industrial one, from self-employed workers to salaried employees, our modern economies are slowly transitioning towards a new model: based on simultaneous collaboration and competition, the boundaries of contemporary organizations are blurring; information technologies are allowing individuals and companies to set base away from cities; shared working spaces are triggering new forms of collaborations between individuals and corporations.This White Paper aims at diagnosing key institutional tensions related to new work practices in the city, and putting forward questions and general propositions likely to overcome these tensions. The idea is to analyze how new collaborative communities and collaborative logics (of coworkers, hackers, makers, fabbers, and teleworkers) and more traditional collective activity and modes of decision making (of the city and corporations in the city) can jointly contribute to the co-production of harmonious new ways of life and new ways of working. Reinventing joint public policies, corporate strategies and citizenship appear here as a key stake where usual dichotomies between private-public, collaborative-non-collaborative economy, traditional citizens and hacktivists need to be overcome.We thus identify in this document a set of controversies around four strong political issues both for the city and the field of management, linked to the emergence of collaborative spaces:o Topic 1. Space, territories, and public policy on collaborative communities in the city;o Topic 2. Collaborative communities and their roles in education in the city;o Topic 3. Business models and their communication in the context of collaborative spaces and collaborative communities;o Topic 4. Collaborative spaces and their roles in innovation and entrepreneurial dynamics at the level of the cityBeyond our controversies, we underline three paradoxes which should be at the heart of new questions for policy-makers, hacktivists, actors of collaborative movements, and citizens (distinctions which may become less and less relevant in the years to come):o Social versus economic orientations of both the city and the collaborative communities it can host;o Critical/revolutionary versus more incremental relationships between cities, organizations, societies, collaborative communities, and new work practices;o Local territory (district/proximate area) grounded versus broader city-oriented or connectivity related issues about collaborative movement and new work practices.To balance these tensions, we elaborate seven general areas of questions and propositions for all stakeholders:o The generalization of infra-organization (physical collaborative platforms);o The emergence of “ ‘inclusive lab’ labels” (elaborated and managed by collaborative communities themselves);o A renewed academic presence in the city and in the country-side (with more virtual, distributed and ‘experiential’ logics);o Ephemeral and mobile labs managed jointly by public, collaborative and private stakeholders;o “Open open” innovation in public and semi-public spaces of the city;o Rise of mega-spaces for creativity in the city;o Development of a global infrastructure for coworkers, mobile workers and teleworkers.These are directions we see as particularly promising to manage the tensions, paradoxes and stakes explicated by our controversies.We hope that these questions and propositions will inspire both academics, politicians, hacktivists and entrepreneurs for future collaborations on the study and joint transformation of public policies, corporate strategies, and citizenship

Association of Early Norepinephrine Administration With 24-Hour Mortality Among Patients With Blunt Trauma and Hemorrhagic Shock

International audienceImportance Hemorrhagic shock is a common cause of preventable death after injury. Vasopressor administration for patients with blunt trauma and hemorrhagic shock is often discouraged. Objective To evaluate the association of early norepinephrine administration with 24-hour mortality among patients with blunt trauma and hemorrhagic shock. Design, Setting, and Participants This retrospective, multicenter, observational cohort study used data from 3 registries in the US and France on all consecutive patients with blunt trauma from January 1, 2013, to December 31, 2018. Patients were alive on admission with hemorrhagic shock, defined by prehospital or admission systolic blood pressure less than 100 mm Hg and evidence of hemorrhage (ie, prehospital or resuscitation room transfusion of packed red blood cells, receipt of emergency treatment for hemorrhage control, transfusion of >10 units of packed red blood cells in the first 24 hours, or death from hemorrhage). Blunt trauma was defined as any exposure to nonpenetrating kinetic energy, collision, or deceleration. Statistical analysis was performed from January 15, 2021, to February 22, 2022. Exposure Continuous administration of norepinephrine in the prehospital environment or resuscitation room prior to hemorrhage control, according to European guidelines. Main Outcomes and Measures The primary outcome was 24-hour mortality, and the secondary outcome was in-hospital mortality. The average treatment effect (ATE) of early norepinephrine administration on 24-hour mortality was estimated according to the Rubin causal model. Inverse propensity score weighting and the doubly robust approach with 5 distinct analytical strategies were used to determine the ATE. Results A total of 52 568 patients were screened for inclusion, and 2164 patients (1508 men [70%]; mean [SD] age, 46 [19] years; median Injury Severity Score, 29 [IQR, 17-36]) presented with acute hemorrhage and were included. A total of 1497 patients (69.1%) required emergency hemorrhage control, 128 (5.9%) received a prehospital transfusion of packed red blood cells, and 543 (25.0%) received a massive transfusion. Norepinephrine was administered to 1498 patients (69.2%). The 24-hour mortality rate was 17.8% (385 of 2164), and the in-hospital mortality rate was 35.6% (770 of 2164). None of the 5 analytical strategies suggested any statistically significant association between norepinephrine administration and 24-hour mortality, with ATEs ranging from –4.6 (95% CI, –11.9 to 2.7) to 2.1 (95% CI, –2.1 to 6.3), or between norepinephrine administration and in-hospital mortality, with ATEs ranging from –1.3 (95% CI, –9.5 to 6.9) to 5.3 (95% CI, –2.1 to 12.8). Conclusions and Relevance The findings of this study suggest that early norepinephrine infusion was not associated with 24-hour or in-hospital mortality among patients with blunt trauma and hemorrhagic shock. Randomized clinical trials that study the effect of early norepinephrine administration among patients with trauma and hypotension are warranted to further assess whether norepinephrine is safe for patients with hemorrhagic shock