ABSTRACT
BACKGROUND: Neurological disorders pose a profound unmet medical need for which new solutions are urgently needed. The consideration of both biological (sex) and socio-cultural (gender) differences between men and women is necessary to identify more efficacious, safer and tailored treatments. Approaches for putting sex and gender medicine into practice have gathered momentum across Europe, but it is currently unclear to what extent they have been implemented in the field of neurology and neuroscience. METHODS: We mapped current activities in research, funding and education aimed at integrating sex and gender consideration in neuroscience and neurology in Europe. We examined and analyzed data gathered from (1) literature searches, (2) policy documents and reports by the European Commission and national funding agencies, (3) web-based searches, (4) "Web of Science", and (5) searches of project databases of funding agencies. An informative / non-systematic search was performed for sections on policies and funding, education, basic research, while a systematic literature and database review was conducted forquantitative analysis of research output and funded projects in terms of sex and gender analysis. RESULTS: Our mapping shows that there is a growing interest and attention towards sex and gender consideration in neurological fields, both from funding agencies and researchers. However, most activities, especially for education, are limited to the individual motivation of researchers and are not organically built within curricula and strategic research priorities. DISCUSSION: We recommend actions that might help increase the consideration of sex and gender specifically in the field of neuroscience and neurology.
ABSTRACT
It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged >50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10-19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2. FLT3 and NPM1 mutations and monocytic morphology occurred more commonly in AML30 than in RAEBT. RAEBT patients were treated less often with induction therapy than AML30, whereas allogeneic stem cell transplant frequency was similar. The median and 4-year OS of RAEBT patients were longer than those of AML30 patients (20.5 vs 12.0 months and 28.6% vs 20.4%, respectively, P = 0.003); this difference in OS was manifested in patients in the intermediate UKMRC karyotype risk group, whereas OS of RAEBT patients and AML30 patients in the adverse karyotype risk group were not significantly different. Multivariable analysis showed that RAEBT (P < 0.0001), hemoglobin (P = 0.005), UKMRC karyotype risk group (P = 0.002), normal BM karyotype (P = 0.004), treatment with induction therapy (P < 0.0001), and stem cell transplant (P < 0.0001) were associated with longer OS. Our findings favor considering de novo RAEBT as a favorable prognostic subgroup of AML.
Subject(s)
Anemia, Refractory, with Excess of Blasts/pathology , Bone Marrow/pathology , Leukemia, Myeloid, Acute/pathology , Age Factors , Aged , Aged, 80 and over , Anemia, Refractory, with Excess of Blasts/genetics , Anemia, Refractory, with Excess of Blasts/mortality , Anemia, Refractory, with Excess of Blasts/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Count , Chromosome Aberrations , DNA Methylation/drug effects , Female , Hematopoietic Stem Cell Transplantation , Humans , Kaplan-Meier Estimate , Karyotype , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Mutation , Neoplasm Proteins/genetics , Neoplastic Stem Cells/pathology , Nuclear Proteins/genetics , Nucleophosmin , Prognosis , Remission Induction , Retrospective Studies , Treatment Outcome , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
Objetivo: Determinar na prática nao só os padroes de uso de suplementaçao com ácido fólico (FA) em pacientes com artrite reumatóide (RA) tratados com metotrexato (MTX) em nosso centro médico, como também o tempo de permanência em uso e toxicidade da droga entre diferentes grupos de pacientes. Métodos: Foi constituído um grupo de 40 pacientes com RA que iniciaram MTX logo após estarem disponíveis os resultados do primeiro estudo de suplementaçao com ácido fólico. Foram obtidos de todos os pacientes, durante três anos, os dados clínico/demográficos e, anualmente, a administraçao e toxicidade acumulada de MTX/FA. Foram examinadas estatísticas descritivas e curvas de sobrevida. Resultados: Três padroes surgiram na prática: pacientes que receberam MTX desde o início (FAO n = 18), aqueles que receberam-no às vezes durante o estudo por causa da toxicidade (FAD n=8) e aqueles que nunca o receberam (FAN n = 14). O tempo global de permanência em uso da droga durante três anos foi de 69 por cento, sendo comparável nos três grupos. Os valores basais MCV (volume corpuscular médio) e os índices de toxicidade acumulada foram maiores entre os pacientes do grupo FAD. Conclusao: Nao foi universal a implementaçao de alteraçoes nas práticas terapêuticas entre nossos clínicos. A permanência em uso da droga foi comparável entre os três grupos terapêuticos. Pacientes que na linha basal tinham MCV anormal ou normal alto deveriam ter suplementaçao com ácido fólico desde o início
