Implications of subcutaneous or intravenous delivery of trastuzumab: further insight from patient interviews in the PrefHer study

BACKGROUND: The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. METHODS: The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. RESULTS: 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). CONCLUSIONS: Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. EUDRACT NUMBER: 2010-024099-25

A proposal for the New Shape Prize: CIVICS: Changing Incentives for Voters in International Cooperation through Sampling

This model is built around the principle that any actor in a global governance institution should have interests aligned with mankind’s. This means creating an incentive structure to make sure that in each different component, every member’s best interest is to faithfully play their role, which is sadly not the case today.Despite widespread awareness of the dangers of inaction on issues such as climate change, policy on the matter evolves very slowly, although a strong majority in most countries would prefer their government do more to prevent or counter its effects (including India, China and the USA). This is only one specific case of humanity agreeing on the need for action (and even often on what needs to be done), only for most policy-makers to shrink from pursuing truly effective policies due to personal or electoral risks and diverse lobbying interests. Current policy-makers do have an advantage, however, in that they are able to spend more time focused on the issue with teams of experts, and have access to more detailed and current information.The goal is then to have decision-makers with the same interests as the general population, but with a decent understanding of the consequences of any decision taken. Once we make sure that the decision-makers are incorruptible, well-intentioned and well-informed, it is enough to design a system by which their decisions are respected and implemented by the international community. This model presents one way of obtaining such a set of decision-makers, and the tools they need to enforce the decisions taken. Our model has a traditional parliamentary structure with some nuances. The upper house is mostly present to bring expertise and guidance from the international community, while the lower house composed of anonymous citizens is in charge of the final decision. An executive council then makes sure that the decisions are respected by all the member countries. We will first explain some recent theoretical and technological developments which are at the heart of the model. Once this is done, we will present its different components and show how the model could be implemented before analyzing its potential weaknesses and their respective solutions

Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study

Aim To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). Patients and methods Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin ® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin ® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation. Results A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients). Conclusions Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected

Personalized and adaptive learning: educational practice and technological impact

Education Technology advances many aspects of learning. More and more learning is taking place online. Learners’ learning behaviors, style, and performance can be easily profiled through learning analytics which collects their online learning footage. It enables and encourages educational research, learning software application development, and online education practices towards personalized and adaptive learning. As we continue to see personalized and adaptive learning progress, we must also pay attention to the negative impacts that feed into our research. In this paper, we will present our introspection of personalized and adaptive learning and argue that it is the social and moral responsibility of educators and institutions to apply personalized and adaptive learning wisely in their education practice. Educators and institutions should also recognize the realistic diversities of individual students’ learning styles and variable learning progress, contextually dependent learning accessibility, and their correspondent support needs for the fine-grained learning activities. We argue that the strategically balanced practices and innovated learning technology are crucial towards an optimized learning experience for the learners. A Tecnologia da Educação avança muitos aspectos da aprendizagem. Cada vez mais aprendizagem está ater lugar online. Os comportamentos de aprendizagem, estilo e desempenho dos aprendentes podem serfacilmente perfilados através de análises de aprendizagem que recolhem as suas filmagens de aprendizagemon-line. Permite e encoraja a investigação educacional, o desenvolvimento de aplicações de software deaprendizagem, e práticas de educação em linha para uma aprendizagem personalizada e adaptativa. À medidaque continuamos a ver progressos na aprendizagem personalizada e adaptativa, devemos também prestaratenção aos impactos negativos que alimentam a nossa investigação. Neste documento, apresentaremos anossa introspecção de aprendizagem personalizada e adaptativa e argumentaremos que é da responsabilidade social e moral dos educadores e instituições aplicar sabiamente a aprendizagem personalizada e adaptativa nasua prática educativa. Os educadores e as instituições devem também reconhecer as diversidades realistas dosestilos de aprendizagem dos estudantes individuais e o progresso variável da aprendizagem, a acessibilidade àaprendizagem contextualmente dependente, e as suas necessidades de apoio correspondente para as actividadesde aprendizagem de grão fino. Argumentamos que as práticas estrategicamente equilibradas e a tecnologiade aprendizagem inovadora são cruciais para uma experiência de aprendizagem optimizada para os alunos

Cambios fonológicos vs obsolescencia lingüística: ¿Cuál es su impacto en la revitalización del rama?

Este estudio presenta una mirada cruzada entre los cambios fonológicos de una lengua en período de extinción y el impacto de esos cambios sobre los esfuerzos de revitalización de la lengua. El trabajo está basado en un estudio de caso del idioma rama el cual se consideraba casi extinto en los años ochenta, y que desde entonces ha sido beneficiado de un programa de descripción, documentación y revitalización. Luego de una presentación de la situación sociolingüística del rama y del contexto en el cual se inscribe el proyecto de revitalización, el fenómeno de obsolescencia lingüística será descrito a través del estudio de la pérdida de un fonema, la nasal velar / ŋ /. Finalmente será analizado el reto que representa para los esfuerzos de revitalización la emergencia de nuevas ‘variantes’ debidas a este tipo de fenómeno de obsolescenci

Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy.

Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease. In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m(2) (equivalent to eribulin 1.23 mg/m(2) [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2-5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m(2) orally twice daily on days 1-14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above. Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05). Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various subgroups of interest, including patients with HER2-negative and triple-negative disease

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

BACKGROUND: Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (SC) trastuzumab, delivered via single-use injection device (SID), over the intravenous (IV) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where SC trastuzumab was delivered via hand-held syringe. PATIENTS AND METHODS: Patients were randomized to receive 4 adjuvant cycles of 600 mg fixed-dose SC trastuzumab followed by 4 cycles of standard IV trastuzumab, or vice versa. The primary endpoint was overall preference proportions for SC or IV, assessed by patient interviews in the evaluable ITT population. RESULTS: A total of 245 patients were randomized to receive SC followed by IV and 243 received IV followed by SC (evaluable ITT populations: 235 and 232 patients, respectively). SC was preferred by 415/467 (88.9%; 95% CI, 85.7-91.6; P<.0001; two-sided test against null hypothesis of 65% SC preference); 45/467 preferred IV (9.6%; 7-13); 7/467 indicated no preference (1.5%; 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled SC and IV periods, respectively (P<.05; 2x2 chi2); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5. CONCLUSION: PrefHer revealed compelling and consistent patient preferences for SC over IV trastuzumab, regardless of SID or hand-held syringe delivery. SC was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared to the known IV profile in EBC. PrefHer and HannaH confirm that SC trastuzumab is a validated and preferred option over IV for improving patients' care in HER2-positive breast cancer

A proposal for the New Shape Prize: CIVICS: Changing Incentives for Voters in International Cooperation through Sampling

International audienceThis model is built around the principle that any actor in a global governance institution should have interests aligned with mankind’s. This means creating an incentive structure to make sure that in each different component, every member’s best interest is to faithfully play their role, which is sadly not the case today.Despite widespread awareness of the dangers of inaction on issues such as climate change, policy on the matter evolves very slowly, although a strong majority in most countries would prefer their government do more to prevent or counter its effects (including India, China and the USA). This is only one specific case of humanity agreeing on the need for action (and even often on what needs to be done), only for most policy-makers to shrink from pursuing truly effective policies due to personal or electoral risks and diverse lobbying interests. Current policy-makers do have an advantage, however, in that they are able to spend more time focused on the issue with teams of experts, and have access to more detailed and current information.The goal is then to have decision-makers with the same interests as the general population, but with a decent understanding of the consequences of any decision taken. Once we make sure that the decision-makers are incorruptible, well-intentioned and well-informed, it is enough to design a system by which their decisions are respected and implemented by the international community. This model presents one way of obtaining such a set of decision-makers, and the tools they need to enforce the decisions taken. Our model has a traditional parliamentary structure with some nuances. The upper house is mostly present to bring expertise and guidance from the international community, while the lower house composed of anonymous citizens is in charge of the final decision. An executive council then makes sure that the decisions are respected by all the member countries. We will first explain some recent theoretical and technological developments which are at the heart of the model. Once this is done, we will present its different components and show how the model could be implemented before analyzing its potential weaknesses and their respective solutions