Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre

Bioreactor for microalgal cultivation systems: strategy and development

Microalgae are important natural resources that can provide food, medicine, energy and various bioproducts for nutraceutical, cosmeceutical and aquaculture industries. Their production rates are superior compared to those of terrestrial crops. However, microalgae biomass production on a large scale is still a challenging problem in terms of economic and ecological viability. Microalgal cultivation system should be designed to maximize production with the least cost. Energy efficient approaches of using light, dynamic mixing to maximize use of carbon dioxide (CO2) and nutrients and selection of highly productive species are the main considerations in designing an efficient photobioreactor. In general, optimized culture conditions and biological responses are the two overarching attributes to be considered for photobioreactor design strategies. Thus, fundamental aspects of microalgae growth, such as availability of suitable light, CO2 and nutrients to each growing cell, suitable environmental parameters (including temperature and pH) and efficient removal of oxygen which otherwise would negatively impact the algal growth, should be integrated into the photobioreactor design and function. Innovations should be strategized to fully exploit the wastewaters, flue-gas, waves or solar energy to drive large outdoor microalgae cultivation systems. Cultured species should be carefully selected to match the most suitable growth parameters in different reactor systems. Factors that would decrease production such as photoinhibition, self-shading and phosphate flocculation should be nullified using appropriate technical approaches such as flashing light innovation, selective light spectrum, light-CO2 synergy and mixing dynamics. Use of predictive mathematical modelling and adoption of new technologies in novel photobioreactor design will not only increase the photosynthetic and growth rates but will also enhance the quality of microalgae composition. Optimizing the use of natural resources and industrial wastes that would otherwise harm the environment should be given emphasis in strategizing the photobioreactor mass production. To date, more research and innovation are needed since scalability and economics of microalgae cultivation using photobioreactors remain the challenges to be overcome for large-scale microalgae production

O sentido olfato no cuidado de enfermagem hospitalar El sentido olfato en la atención de enfermería hospitalar The olfactory sense in a hospital nursing care

O objetivo deste estudo foi identificar as percepções e reações relacionadas ao sentido olfato durante o cuidado. Apresenta o resultado de três pesquisas de doutorado sobre as pistas olfativas na compreensão das alterações clínicas e padrão de cuidado de enfermagem em setores hospitalares. Estudo exploratório, descritivo, com abordagem qualitativa valorizando princípios do método Sociopoético e dos Sentidos Sociocomunicantes do Corpo. Os sujeitos utilizam o sentido olfato como instrumento para: diagnosticar os desvios de saúde fisiológicos e psicoafetivos; avaliar o estado de higiene, de limpeza corporal do paciente e do ambiente; e nortear o cuidado de enfermagem necessário. Identificamos repulsa pelo mau odor que emana do paciente e as estratégias utilizadas para minimizá-lo. Possibilitou-se instituir um espaço de diálogo para conhecer as reações aos odores, reconhecer as próprias limitações aos estímulos olfativos e redimensionar os mecanismos de respostas que possibilitem o conforto e a segurança dos envolvidos no cuidado de enfermagem.<br>El objetivo es identificar las percepciones y reacciones relacionadas al sentido del olfato en la atención de enfermería hospitalaria. Presenta los resultados de tres investigaciones de doctorado que centran sus datos sobre el sentido olfato a partir de la atención de enfermería hospitalaria en el trauma ortopédico, clínica quirúrgica y centro quirúrgico. Son estudios exploratorios, con enfoque cualitativo, utilizando los principios del método Sociopoético y Sentidos Sociocomunicantes. La transversalidad de los datos muestra el uso del olfato como herramienta para la atención, para evaluar el estado de higiene y limpieza del paciente y medio ambiente, e identifica rechazado por el mal olor que emana del paciente. Permiten reconocer esas reacciones a los olores de sus pacientes y el medio ambiente, para el reconocimiento de sus propias limitaciones a los estímulos y desarrollar mecanismos de respuesta que permiten la comodidad y seguridad de las personas involucradas en la atención.<br>The goal is to identify the perceptions and reactions related to the olfactory sense in the care provided. It presents the results of three doctoral researches on olfactory cues in understanding the clinical and standard variations of nursing care in hospital sectors. It's an exploratory and descriptive study with a qualitative approach, emphasizing the principles of Sociopoetic method and the body socio-communicating senses. It shows the use of this as a tool to diagnose the physiological and psychoaffective health deviations; assess the state of hygiene, the cleaning of patient's body and environment and to guide the nursing care needed. It was identified the repulse for the bad smell emanating from the patient and the strategies used to minimize them. Allowed to set up a space for dialogue to see the reactions to odors, recognize their own limitations on olfactory stimuli and adjust the response mechanisms that enable the comfort and safety of those involved in nursing care