The effectiveness of ibrutinib in chronic lymphocytic leukaemia: a nationwide, population-based study in the Netherlands

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High-dose posaconazole for azole-resistant aspergillosis and other difficult-to-treat mould infections

Background: Oral follow-up therapy is problematic in moulds with reduced azole-susceptibility, such as azole-resistant Aspergillus fumigatus infection. Currently, only intravenous liposomal amphotericin B (L-AmB) is advocated by guidelines for the treatment of azole-resistant aspergillosis infections. Preclinical research indicates that high-dose posaconazole (HD-POS) might be a feasible option provided that high drug exposure (ie POS serum through levels >3 mg/L) can be achieved and is safe. Objectives: To describe our experience with the use of oral HD-POS as treatment strategies for patients infected with pathogens with a POS MIC close to the clinical breakpoint. Patients/Methods: We review evidence supporting the use of HD-POS and describe our experience on safety and efficacy in 16 patients. In addition, we describe the adverse events (AE) observed in 25 patients with POS concentrations at the higher end of the population distribution during treatment with the licensed dose. Results: Sixteen patients were treated intentionally with HD-POS for voriconazole-resistant invasive aspergillosis (7/16), mucormycosis (4/16), salvage therapy for IA (4/16) and IA at a sanctuary site (spondylodiscitis) in 1. Grade 3-4 AEs were observed in 6, and all of them were considered at least possibly related. Grade 3-4 AEs were observed in 5 of the 25 patients with spontaneous high POS serum through levels considered at least possibly related using Naranjo scale. Conclusions: High-dose posaconazole is a treatment option if strict monitoring for both exposure and for AE is possible

Impact of red blood cell transfusion dose density on progression-free survival in lower-risk myelodysplastic syndromes patients

Progression-free survival of lower-risk myelodysplastic syndromes patients treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals of newly diagnosed lower-risk myelodysplastic syndromes patients from 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860

Editorial: Knowledge of gastrointestinal toxicity mechanisms is paving the way for improved assessment and management of patient supportive care

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Interdisciplinary education affects student learning: a focus group study.

BACKGROUND: In order to best prepare medical students for their increasingly complex future career, interdisciplinary higher education is swiftly gaining popularity. However, the implementation of interdisciplinary learning in medical education is challenging. The present study deepens the understanding of the challenges and opportunities inherent to the implementation of an interdisciplinary course. We elucidated the attitudes and beliefs of students participating in a newly developed interdisciplinary minor, in which students of medicine (MS) and communication and information sciences (CISS) were involved. METHODS: We conducted four semi-structured focus group interviews, of which two were held before, and two were held after the course. Seven MS and six CISS participated voluntarily. A pre-arranged interview guide was used. The interviews were recorded and afterwards systematically analyzed with the 'constant comparative analysis' technique. RESULTS: The focus group interviews revealed three differences in epistemics between students in terms of 1) curriculum content, 2) educational formats and 3) student's competence perceptions. These factors influenced the way students evaluated themselves, each other and the interdisciplinary course. CONCLUSIONS: We conclude that factors that influence interdisciplinary learning are personal epistemics, individual learning preferences, and the synergy that is achieved throughout interdisciplinary learning. Organizing the dialogue among students of different disciplines could make students aware of inequalities, implicated biases and assigned status of different student groups. These empirical results are crucial to tailor interdisciplinary education to each specific discipline and to take interdisciplinary learning to a higher level of maturity

Severe fatigue after treatment for childhood cancer (Review)

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Successful treatment of a PNH patient non-responsive to eculizumab with the novel complement C5 inhibitor coversin (nomacopan)

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Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL)

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed