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Background: In the field of research, psychological safety has been widely recognized as a contributing factor to improving the quality of care and patient safety. However, its consideration in the curricula and traineeship pathways of residents and health care students is scarce., Objective: This study aims to determine the extent to which health care trainees acquire psychological safety competencies during their internships in clinical settings and identify what measures can be taken to promote their learning., Methods: A mixed methods observational study based on a consensus conference and an open-ended survey among a sample of health care trainee mentors from health care institutions in a pan-European context was conducted. First, we administered an ad hoc questionnaire to assess the perceived degree of acquisition or implementation and significance of competencies (knowledge, attitudes, and skills) and institutional interventions in psychological safety. Second, we asked mentors to propose measures to foster among trainees those competencies that, in the first phase of the study, obtained an average acquisition score of <3.4 (scale of 1-5). A content analysis of the information collected was carried out, and the spontaneity of each category and theme was determined., Results: In total, 173 mentors from 11 pan-European countries completed the first questionnaire (response rate: 173/256, 67.6%), of which 63 (36.4%) participated in the second consultation. The competencies with the lowest acquisition level were related to warning a professional that their behavior posed a risk to the patient, managing their possible bad reaction, and offering support to a colleague who becomes a second victim. The mentors' proposals for improvement of this competency gap referred to training in communication skills and patient safety, safety culture, work climate, individual attitudes, a reference person for trainees, formal incorporation into the curricula of health care degrees and specialization pathways, specific systems and mechanisms to give trainees a voice, institutional risk management, regulations, guidelines and standards, supervision, and resources to support trainees. In terms of teaching methodology, the mentors recommended innovative strategies, many of them based on technological tools or solutions, including videos, seminars, lectures, workshops, simulation learning or role-playing with or without professional actors, case studies, videos with practical demonstrations or model situations, panel discussions, clinical sessions for joint analysis of patient safety incidents, and debriefings to set and discuss lessons learned., Conclusions: This study sought to promote psychological safety competencies as a formal part of the training of future health care professionals, facilitating the translation of international guidelines into practice and clinical settings in the pan-European context., (©Irene Carrillo, Ivana Skoumalová, Ireen Bruus, Victoria Klemm, Sofia Guerra-Paiva, Bojana Knežević, Augustina Jankauskiene, Dragana Jocic, Susanna Tella, Sandra C Buttigieg, Einav Srulovici, Andrea Madarasová Gecková, Kaja Põlluste, Reinhard Strametz, Paulo Sousa, Marina Odalovic, José Joaquín Mira. Originally published in JMIR Medical Education (https://mededu.jmir.org), 07.10.2024.)

Background: A lower dosage of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) has shown efficacy in managing short-term toxicity and maintaining a deep molecular response in patients who fail to achieve treatment-free remission., Method: From over 700 patients with CML who were treated at two centres over the last three decades, this retrospective study identified eight patients characterised by long-term treatment failure and simultaneous prolonged significant haematologic toxicity that prevented the use of the standard tyrosine kinase inhibitor dosage., Results: Patients had a high or intermediate ELTS risk score, and most had significant comorbidities. Two patients were treated previously with busulfan, and four were aged over 70, which might explain the reduced pool of normal haematopoietic stem cells. However, concomitant myelodysplastic syndrome or the presence of clonal haematopoiesis of indeterminate potential was not demonstrated. Despite prolonged treatment failure, the survival of these patients (who were ineligible for stem cell transplantation) ranged from 45-396 months. Neither mutations in the ABL kinase domain nor additional cytogenetic abnormalities developed during the treatment of these patients, prompting speculation about the low selective pressure of low-dose tyrosine kinase inhibitors and/or the absence of mutations at diagnosis., Conclusion: It is important not to stop treatment with tyrosine kinase inhibitors at a low personalised dosage in CML patients with prolonged significant haematologic toxicity despite long-term treatment failure., Competing Interests: Conflicts of interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. EF declared support not associated with the preparation of the manuscript: Novartis – supported lectures, member of the local advisory board; Angelini – supported lectures; Zentiva – supported lectures, member of the advisory board; ELN Foundation – travel support, HPST – travel support., (Copyright © 2024 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

The COVID-19 pandemic led to the implementation of interventions to provide emotional and psychological support to healthcare workers in many countries. This ecological study aims to describe the strategies implemented in different countries to support healthcare professionals during the outbreak. Data were collected through an online survey about the measures to address the impact of the pandemic on the mental health of healthcare workers. Healthcare professionals, researchers, and academics were invited to respond to the survey. Fifty-six professionals from 35 countries contributed data to this study. Ten countries (28.6%) reported that they did not launch any national interventions. Both developed and developing countries launched similar initiatives. There was no relationship between the existence of any type of initiative in a country with the incidence, lethality, and mortality rates of the country due to COVID-19, and per capita income in 2020. The 24 h hotline for psychological support was the most frequent intervention. Tools for self-rescue by using apps or websites were extensively used, too. Other common interventions were the development of action protocols, availability of regular and updated information, implantation of distance learning systems, early detection of infection programs for professionals, economic reinforcements, hiring of staff reinforcement, and modification of leave and vacation dates.

The information about chronic myeloid leukemia (CML) patients with a deep molecular response of ≥ 4.5 log reduction (MR 4.5 ) in whom the dose of imatinib (IM) had to be reduced to relieve toxicity is insufficient. In 205 CML patients the dose of IM was reduced in 19 (31.2%) out of 61 patients with MR 4.5 . The patients (12 pretreated with interferon-alpha) achieved MR 4.5 after an average of 27.7 months. The duration of MR 4.5 before the reduction of the dose was 16-123 (mean = 56.7) months. After the IM reduction (200 mg daily to 400 mg twice weekly for 15-90 (mean = 48) months) MR 4.5 or major molecular response (MMR) was maintained in 14 (73.7%) and 2 (10.5%) patients, respectively. Three patients who lost MMR (15.8%) after the discontinuation of IM regained MR 4.5 after the reintroduction of a lower dose. A lower dosage of IM should be tested for the management of side effects in patients with MR 4.5 in prospective studies.

Elderly patients with hematological malignancies are often reliant on allogeneic transplantations. Older family relatives are increasingly involved in utilization as PBSC donors. We analyzed the mobilization results from 103 donors of age ≥55 years in comparison with 121 younger donors of age <55 years. The median CD34+ count in peripheral blood on day +5 of the mobilization was higher in younger than in older donor group (72.0 vs. 37.0 cells/μL, P < 0.0001). Linear regression showed a negative correlation between the age and CD34+ count in peripheral blood (P < 0.0001) and apheresis product (P < 0.0001). Based on multivariate analysis, the amount of circulating CD34+ cells appeared to be negatively influenced by age (P < 0.001) and positively by the preapheresis WBC count (P < 0.001). The precollection CD34+ (P < 0.0001), PLT (P = 0.0144) counts, and age (P = 0.0392) were confirmed as independent factors determining the collection yield. The side effects of G-CSF administration were similar in both the groups. Apheresis complications were more frequently recorded in elderly donors (29 vs. 15%, P = 0.0096). Higher age represents a risk factor for poorer mobilization results. A requirement for more than one apheresis in older donors occurs more frequently to obtain the adequate amount of CD34+ cells. Mobilization and collection procedures are associated with acceptable risks and complication rates in elderly donors., (Copyright © 2010 Wiley-Liss, Inc.)

Expression of major cytochrome P450 forms (P450) was followed in preparation of purified hematopoietic CD34+ stem and progenitor cells. Levels of transcripts as well as mature proteins were traced by quantitative real-time polymerase chain reaction and by Northern and Western blotting. P450 1B1 and P450 2E1 proteins and respective mRNAs were found in all cases. On the other hand, no expression of P450 3A4, P450 3A7, and P450 2C9 was found. The results showed that expression of various P450 enzymes starts at different stages of cell differentiation. Both P450 forms found are known to be connected with cancer cells and with activation of procarcinogens (P450 1B1, polycyclic aromatic hydrocarbons; P450 2E1, nitrosamines, and solvents). Hence, cells at the early stage of differentiation already may be influenced by interaction with xenobiotics. This fact should also be taken into consideration when hematopoietic cell transplant therapy is applied.

Human CD34+ cells (haematopoietic stem and progenitor cells separated from peripheral blood) were shown to express CYP2E1 protein by Western blotting. For the first time, the specific CYP2E1 activity (chlorzoxazone 6-hydroxylation) was also detected. No CYP3A4 protein neither the CYP3A-specific nifedipine oxidase activity were detectable. The results obtained indicate differences in content of active CYP proteins in populations of stem and progenitor cells from different species as the CYP3A2 (a rat form similar to human CYP3A4) was shown to be expressed in bone marrow derived cells by RT-PCR (Avital et al. 2001).