Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome

Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival. TP53 mutations were detected in 230 (10.5%) patients with AML/MDS-EB with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was observed in 174 (76%) patients. Multiple TP53 mutations were found in 49 (21%) patients. Concurrent mutations were detected in 113 (49%) patients. No significant difference in any of the aforementioned molecular characteristics of mutant TP53 was detected between AML and MDS-EB. Patients with mutant TP53 have a poor outcome (2-year overall survival, 12.8%); however, no survival difference between AML and MDS-EB was observed. Importantly, none of the molecular characteristics were significantly associated with survival in mutant TP53 AML/MDS-EB. In most patients, TP53 mutations remained detectable in complete remission by deep sequencing (73%). Detection of residual mutant TP53 was not associated with survival. Mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity

Verpleegkundige interventies in een tastbaar verleden

Uiteenzetting van de missie en visie van het Historisch College FNI, over de rol en geschiedenis van de verpleegkundige. Dit ter ondersteuning van beleidsvorming en de invloed die de beroepsgroep daarop heef

Preferences of GPs and patients for preventive osteoporosis drug treatment: a discrete-choice experiment

BACKGROUND: Osteoporotic fractures have a serious economic impact on society and on the quality of life of patients. Differences in opinions on the desirability of preventive treatment initiation may hamper the process and outcome of shared decision making between physician and patient. OBJECTIVE: To evaluate and compare preferences of GPs and patients for preventive osteoporosis drug treatment. METHODS: Discrete-choice experiment (DCE) involving 34 general practices in the area of Rotterdam, the Netherlands. Participants included 40 GPs and 120 women aged > or = 60 years who participated in a study on osteoporosis case finding. We included any woman aged >60 years, with an over-representation of women with a high fracture risk (n = 60). OUTCOMES: (i) The relative weights that GPs and patients place on five treatment attributes of preventive osteoporosis drug treatment: effectiveness, nausea as an adverse effect, total treatment duration, route of drug administration and out-of-pocket costs; and (ii) the determinants of any differences in preferences between GPs and patients. RESULTS: The response rate was 40/59 (68%) for GPs and 120/181 (66%) for patients. All treatment attributes proved to be important for preferences of GPs and patients. GPs had a significantly less favourable attitude towards preventive osteoporosis drug treatment than patients; they placed significantly higher values on effectiveness of preventive drug treatment and short total preventive treatment duration than patients. CONCLUSIONS: GPs and patients showed different preferences towards preventive osteoporosis drug treatment. Addressing each of these differences may have a positive effect on the process and outcomes of shared decision making regarding preventive treatment initiatio

Preferences of GPs and Patients for Preventive Osteoporosis Drug Treatment: A Discrete-Choice Experiment

Background: Osteoporotic fractures have a serious economic impact on society and on the quality of life of patients. Differences in opinions on the desirability of preventive treatment initiation may hamper the process and outcome of shared decision making between physician and patient. Abstract: Objective: To evaluate and compare preferences of GPs and patients for preventive osteoporosis drug treatment. Abstract: Methods: Discrete-choice experiment (DCE) involving 34 general practices in the area of Rotterdam, the Netherlands. Participants included 40 GPs and 120 women aged ≥60 years who participated in a study on osteoporosis case finding. We included any woman aged >60 years, with an over-representation of women with a high fracture risk (n - 60). Abstract: Outcomes: (i) The relative weights that GPs and patients place on five treatment attributes of preventive osteoporosis drug treatment: effectiveness, nausea as an adverse effect, total treatment duration, route of drug administration and out-of-pocket costs; and (ii) the determinants of any differences in preferences between GPs and patients. Abstract: Results: The response rate was 40/59 (68%) for GPs and 120/181 (66%) for patients. All treatment attributes proved to be important for preferences of GPs and patients. GPs had a significantly less favourable attitude towards preventive osteoporosis drug treatment than patients; they placed significantly higher values on effectiveness of preventive drug treatment and short total preventive treatment duration than patients. Abstract: ConclusionsConclusions GPs and patients showed different preferences towards preventive osteoporosis drug treatment. Addressing each of these differences may have a positive effect on the process and outcomes of shared decision making regarding preventive treatment initiation.