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Bansal explores how systems‐based enquiry might productively shift focus from individual success or failure, to broader support of wellbeing and burnout prevention. [ABSTRACT FROM AUTHOR]

The involvement of non‐researcher contributors (eg, stakeholders, patients and the public, decision and policy makers, experts, lay contributors) has taken a variety of forms within evidence syntheses. Realist reviews are a form of evidence synthesis that involves non‐researcher contributors yet this practice has received little attention. In particular, the role of patient and public involvement (PPI) has not been clearly documented. This review of reviews describes the ways in which contributor involvement, including PPI, is documented within healthcare realist reviews published over the last five years. A total of 448 papers published between 2014 and 2019 were screened, yielding 71 full‐text papers included in this review. Statements about contributor involvement were synthesized across each review using framework analysis. Three themes are described in this article including nomenclature, nature of involvement, and reporting impact. Papers indicate that contributor involvement in realist reviews refers to stakeholders, experts, or advisory groups (ie, professionals, clinicians, or academics). Patients and the public are occasionally subsumed into these groups and in doing so, the nature and impact of their involvement become challenging to identify and at times, is lost completely. Our review findings indicate a need for the realist review community to develop guidance to support researchers in their future collaboration with contributors, including patients and the public. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are hematopoietic stem cell malignancies associated with an erythroid maturation defect, resulting in anemia. Treatments for MDS include erythropoiesis-stimulating agents (ESAs). The identification of prognostic markers is important to help predict response and improve outcomes. Various scoring systems have been developed to help predict response to ESAs. Despite limitations in its assessment, serum erythropoietin (sEPO) level is an important predictor of hematologic response to ESAs in patients with lower-risk MDS. Numerous studies have reported significantly lower sEPO levels among responders versus non-responders. Furthermore, treatment response is significantly more likely among those with sEPO levels below versus those above various cutoffs. Other prognostic indicators for response to ESAs include lower transfusion requirement, fewer bone marrow blasts, higher hemoglobin, lower serum ferritin, lower-risk MDS, and more normal cytogenetics. Studies of other MDS therapies (e.g., lenalidomide and luspatercept) have also reported that lower sEPO levels are indicative of hematologic response. In addition, lower sEPO levels (up to 500 IU/L) have been included in treatment algorithms for patients with lower-risk MDS to define whether ESAs are indicated. Lower sEPO levels are predictive of hematologic response-particularly to ESAs. Further, clinical trials should use sEPO thresholds to ensure more homogeneous cohorts. [ABSTRACT FROM AUTHOR]

Attributing value to teaching work has been problematic, but here Park et al. offer holistic reframing as a potential solution. [ABSTRACT FROM AUTHOR]

Context: Globally, primary health care is facing workforce shortages. Longer and higher‐quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community‐based teaching settings. Methods: Semi‐structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo‐assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. Results: Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. Conclusions: This research demonstrates the marginalisation of primary care‐based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community‐based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care. The authors demonstrate, through use of Communities of Practice theory, ways to improve retention and recruitment of community‐based clinical teachers. [ABSTRACT FROM AUTHOR]

Summary: Many patients with lower‐risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis‐stimulating agents (ESAs) and their biosimilars are used to treat anaemia in MDS and, currently, epoetin alfa and darbepoetin alfa are commonly used and recommended by clinical guidelines. To better understand the evidence available on the use of ESAs for anaemia in lower‐risk MDS, we conducted a systematic literature review to identify randomized and nonrandomized prospective studies reporting on clinical efficacy/effectiveness, patient‐reported quality of life (QoL), and safety. We extended our review to include retrospective studies for darbepoetin alfa specifically and to ascertain the feasibility of completing an indirect network meta‐analysis comparing epoetin and darbepoetin alfa. Overall, 53 articles reporting on 35 studies were included. The studies indicated a clinical benefit of ESAs, with benefits observed across key clinical outcomes. ESAs showed consistent improvement in erythroid response rates (ESA‐naïve, 45–73%; previous ESA exposure, 25–75%) and duration of response. Comparative studies demonstrated similar progression to acute myeloid leukaemia and several showed improved overall survival and QoL. Limited safety concerns were identified. This analysis confirmed ESA therapy should be the foremost first‐line treatment of anaemia in most patients with lower‐risk MDS who lack the 5q deletion. [ABSTRACT FROM AUTHOR]

The challenge faced by newly graduated nurses from undergraduate study to practice is a persistent theme in nursing practice literatures. However, there is a lack of understanding about how this transition happens. This focused ethnographic study explored how newly graduated nurses (novices) interacted with experienced nurses and learnt in a hospital ward in Singapore. Using the 'Trajectory of identification framework' developed from Wenger's Community of Practice theory, data was collected through observation and focused group discussions. This research revealed the participating rules as the sociocultural characteristics of the nursing community, and how these characteristics are ongoingly negotiated among the nurses. The nurses' changing performative competence and identity in different situations are conceptualised as the 'Participation Space'. This study also showed how concepts of Community of Practice theory can be analytically applied and further developed in empirical study. Specifically, a conceptual 'Participation Matrix' is theorised which adds an additional tool to understand the nurses' dynamic participation and negotiation of membership in a Community of Practice. Novices' transition should be viewed as an ongoing dynamic workplace learning, through which negotiation of performative competence and identity among members take place. The soon to be novices and workplaces should be prepared with this understanding. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and meta-analysis to estimate the efficacy of darbepoetin alpha ( DA) for treatment of myelodysplastic syndrome ( MDS)-related anaemia. Eligible studies were prospective, interventional, and reported World Health Organization, French-American-British, or International Prognostic Scoring System ( IPSS) criteria. Outcomes included erythroid response rate (primary); haemoglobin response; change in haemoglobin, transfusion status, and quality-of-life (QoL); and safety. Ten studies ( N = 647) were analysed. Erythroid response rate range was 38-72%; median response duration range was 12-51+ months. Patients with erythropoietin ( EPO) <100 iu/l had 35% [95% confidence interval ( CI): 22-48%; P < 0·001) better response than patients with EPO >100 iu/l. Erythropoesis-stimulating agent ( ESA)-naïve patients had 17% (95% CI: 3-32%; P = 0·022) greater response rate than those previously treated with ESA. Nonetheless, previously treated patients had response rates of 25-75%. Higher baseline haemoglobin levels, higher dose, transfusion-independence and low-risk IPSS status were reported by several studies to be associated with better response. QoL, transfusion rates and haemoglobin levels improved with treatment. Hypertension, thromboembolism and progression to acute myeloid leukaemia were reported in 2%, 1% and 1% of patients, respectively. This meta-analysis suggests that DA treatment can be useful for improving erythroid response in MDS patients with anaemia, even among patients previously treated with ESA. [ABSTRACT FROM AUTHOR]

Background: General practice is increasingly used as a learning environment in undergraduate medical education in the UK. Aim: The aim of this project was to identify, summarise and synthesise research about undergraduate medical education in general practice in the UK. Methods: We systematically identified studies of undergraduate medical education within a general practice setting in the UK from 1990 onwards. All papers were summarised in a descriptive report and categorised into two in-depth syntheses: a quantitative and a qualitative in-depth review. Results: 169 papers were identified, representing research from 26 UK medical schools. The in-depth review of quantitative papers (n = 7) showed that medical students learned clinical skills as well or better in general practice settings. Students receive more teaching, and clerk and examine more patients in the general practice setting than in hospital. Patient satisfaction and enablement are similar whether a student is present or not in a consultation, however, patients experience lower relational empathy. Two main thematic groups emerged from the qualitative in-depth review (n = 10): the interpersonal interactions within the teaching consultation and the socio-cultural spaces of learning which shape these interactions. The GP has a role as a broker of the interactions between patients and students. General practice is a socio-cultural and developmental learning space for students, who need to negotiate the competing cultures between hospital and general practice. Lastly, patients are transient members of the learning community, and their role requires careful facilitation. Conclusions: General practice is as good, if not better, than hospital delivery of teaching of clinical skills. Our meta-ethnography has produced rich understandings of the complex relationships shaping possibilities for student and patient active participation in learning. [ABSTRACT FROM PUBLISHER]

Iron is an essential element to the well functionning of the organism and requires careful maintenance of its homeostasis. This is mainly due to hepcidin, a hormone secreted by the liver that controls the flow of iron within the body. It has a hyposideremic action by reducing the expression of ferroportin, the only protein known to this day, which can export iron into the extracellular environment. This has the effect of decreasing intestinal absorption and increasing intracellular retention, especially in macrophages. Hepcidin is stimulated by elevation of iron and inflammation while activation of erythropoiesis inhibits it. Understanding its regulation allows a better understanding of the pathophysiological mechanisms of overload diseases and iron deficiency. Therefore, hepcidin analysis is interesting for the exploration of iron homeostasis. In combination with other biological parameters of iron status, it is possible to find better instructions for therapeutic managements of iron metabolism diseases. Thus, an assaying method by coupling liquid chromatography and tandem mass spectrometry has been implemented at Grenoble University Hospital and the analytical performances of this assay met the laboratory requirements in terms of reliability of the analysis. [ABSTRACT FROM AUTHOR]

The authors express their opinions regarding the article "The 'missing person' in roles-based competency models: a historical, cross-national, contrastive case study" by C. Whitehead, V. Selleger, J. van de Kreeke, and B. Hodges. They discuss the debate concerning competency-based frameworks in clinical education, the critical discourse analysis methods of theorist Michel Foucault, and the focus on doctors or patients as the subject in care.

The bone marrow niche plays an increasing role in the pathophysiogenesis of myelodysplastic syndromes. More specifically, mesenchymal stromal cells, which can secrete extracellular vesicles and their miRNA contents, modulate the fate of hematopoietic stem cells leading to leukemogenesis. Extracellular vesicles can mediate their miRNA and protein contents between nearby cells but also in the plasma of the patients, being potent tools for diagnosis and prognostic markers in MDS. They can be targeted by antisense miRNA or by modulators of the secretion of extracellular vesicles and could lead to future therapeutic directions in MDS. [ABSTRACT FROM AUTHOR]

Objectives and methods Chronic myelomonocytic leukemia ( CMML) is a severe disease for which allogeneic stem cell transplantation (allo- SCT) remains the only potentially curative treatment. We describe a retrospective study determining prognostic factors for outcome after allo- SCT in consecutive 73 patients with CMML reported to the SFGM- TC registry between 1992 and 2009. Results At diagnosis, median age was 53 yrs, and 36% patients had palpable splenomegaly (SPM). 48, 13, and 9 patients had good, intermediate, and poor risk karyotype, respectively, according to IPSS, 61% patients had CMML-1, and 39% had CMML-2. 41/31/1 cases had an HLA-identical sibling, an unrelated and haploidentical donor, respectively. 43 patients received reduced-intensity conditioning. With a median follow-up of 23 month, acute grade 2-4 and chronic GVHD developed in 21 and 25 patients, respectively. The 3-year OS, NRM (non-relapse mortality), EFS, and CIR (cumulative incidence of relapse) were 32%, 36%, 29% and 35%, respectively. OS was not influenced by the CR status, marrow blasts% at allo-SCT, prior treatments, and cGVHD. Using multivariate analysis, year of transplant < 2004 ( YOT) ( P = 0.005) was associated with higher NRM, YOT < 2004 ( P = 0.04) and SPM at allo- SCT ( P = 0.02) with lower EFS, and YOT < 2004 ( P = 0.03) and SPM at allo- SCT ( P = 0.04) with poorer OS. Conclusions Allogeneic stem cell transplantation is a valid treatment option for patients with CMML, and its outcome has improved with YOT > 2004. Splenomegaly seems to be a negative factor of OS and EFS in this series. [ABSTRACT FROM AUTHOR]

Marrow cells from patients with higher-risk myelodysplastic syndrome ( MDS) exhibit constitutive nuclear factor ( NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m2, days 1, 4, 8 and 11) and low dose cytarabine arabinoside ( LDAC; 10 mg/m2, then 20 mg/m2 from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response ( CR, n = 1), marrow- CR ( n = 3), partial response ( PR, n = 5) and haematological improvement ( HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients ( P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow- CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes. [ABSTRACT FROM AUTHOR]

Medical Education 2012: 46: 372-380 Context Text is familiar to us all. This paper offers an introduction to, and an exploration of, the range of methodological possibilities open to the education researcher who has chosen to use text as a research data source. It encourages a purposeful deliberation of the different textual sources available as data, the range of methodological approaches possible and the types of interpretation that can be adopted when embarking on an empirical study using textual data. Methods Approaches to interpreting text are varied and utilise a range of analytical and interpretative strategies. To illustrate the theoretical points raised within this paper, two contrasting methods were applied to the same text. Tag cloud analysis and performative narrative analysis (PNA) were employed to analyse Chapter 4 of the UK government's 2010 White Paper Equity and excellence: Liberating the NHS. Results The adoption of these contrasting methodologies, which are not currently used extensively in medical education research, revealed that some common issues were identified by both tag clouds and PNA, but, in addition, each approach was able to unveil something unique about the text. Conclusions These two methods highlight the range of affordances, or possibilities, that textual analysis will have on the results. We suggest that medical education researchers should be encouraged to move away from the current dominant and privileged methodologies that seek to provide answers and explore other methods and approaches to textual data that encourage us to question and reflect more deeply. [ABSTRACT FROM AUTHOR]

Abstract: ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10g/dl, serum EPO<500UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9g/dl, and serum EPO<100UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p =0.01), lower serum EPO (p =0.04) and WHO diagnosis of RCMD-RS (p =0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA <6 months and ≥6 months from diagnosis (p =0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point. [ABSTRACT FROM AUTHOR]

Healthcare education spans a range of institutional "homes", from vocational colleges, practice-based organizations, to the university-based academy. The Dearing Report in the UK [[6]] in contrast, promoted the "scholarship of education" advocating inclusion of educational activities as markers of academic excellence and quality. Many institutions have responded to and supported these developments in positive ways providing, for example, both teaching and research scholarship promotion pathways, and supporting scholarly professionalization of teachers such as the Higher Education Academy fellowship framework, or postgraduate masters and doctoral programs. [Extracted from the article]

Rituximab treatment of B-cell lymphoproliferative disease following transplantation is being evaluated. We describe an Epstein -- Barr virus-related B-cell lymphoma that developed in a 55-year-old woman, one year after autologous transplantation for relapsing angioimmuno-blastic T-cell lymphoma. Complete remission was achieved after four cycles of rituximab and reduced-dose CHOP. This case is discussed in the context of severe immunodepression. Monoclonal anti-CD20 antibodies might restore a balance between T-cell immunosurveillance and EBV proliferation in B-cells. [ABSTRACT FROM AUTHOR]

Erythroleukemia is, within FAB classification, a proliferation of erythroblasts superior to 50% and of myeloblasts superior to 30%. The new WHO classification abolishes the frontier between RAEB-t with 20% and leukemia with 30% of blasts. AML6 variant is a new entity characterized by the proliferation of immature erythroblasts and the absence of non-erythroid blast cells. We analyzed 16 erythroleukemia, 5 RAEB-t and 2 AML6 variants to clarify their relationship.We suggest on survival, karyotype and cytologic characteristics that secondary erythroleukemia are the same entity as RAEB-t, confirming the WHO classification and that amongst de novo erythroleukemia, there is ‘AML6 variant’ with pure erythroid lineage proliferation. [Copyright &y& Elsevier]

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders predominating in older patients, characterized by ineffective hematopoiesis leading to cytopenias and by frequent acute myeloid leukemia (AML) transformation [[1]]. We compared outcomes of patients with MDS-RS and MDS without RS included in our ESA failure cohort (Park et al. [[7]]), from ESA introduction and after ESA failure. HMA treatment was correlated with AML progression, even though we had carefully eliminated patients having progressed to high and very high IPSS-R at ESA failure, as in our previous large series on MDS-RS and non MDS-RS patients [[7]]. [Extracted from the article]

This article offers information on the Special Interest Group in Educational Research (SIGER) and the Doctoral Student Network, two new groups within the Society of Academic Primary Care (SAPC). The groups seek to respond to the challenges associated with primary care educational research. The importance of primary care education research is explored.

The article presents a study on the use of the thrombopoietin receptor agonist romiplostim in managing Immune Thrombocytopenic Purpura (ITP). It notes that the findings of the study reveal that romiplostim induction will contribute to a rapid normalization of the platelet count while a relapse will occur if this will be discontinued. This drug is also used to diagnose a non-Hodgkin lymphoma through a tissue sample biopsy.

A letter to the editor is presented, which discusses a case of a 50-year-old male patient diagnosed with Waldenström macroglobulinemia (WM) and examines the effect of rituximab in his treatment.

This article was originally published without an Open Access but due to the authors final decision to opt for Open Choice this correction was created. [ABSTRACT FROM AUTHOR]

Remote consulting has become part of the medical student clinical experience in primary care, but little research exists regarding the impact on learning. To describe the experiences of General Practitioner (GP) educators and medical students in using student-led remote consultations as an educational tool. A qualitative, explorative study conducted at four UK medical schools. GP educators and medical students were purposively sampled and interviewed. Nine themes arose: practical application, autonomy, heuristics, safety, triage of undifferentiated patients, clinical reasoning, patient inclusion in student education, student–patient interaction, and student–doctor interaction. Remote consulting has become part of the clinical placement experience. This has been found to expose students to a wider variety of clinical presentations. Verbal communication, history-taking, triage, and clinical reasoning skills were practised through remote consulting, but examination skills development was lacking. Students found building rapport more challenging, although this was mitigated by having more time with patients. Greater clinical risk was perceived in remote consulting, which had potential to negatively impact students' psychological safety. Frequent debriefs could ameliorate this risk and positively impact student–doctor relationships. Student autonomy and independence increased due to greater participation and responsibility. Pre-selection of patients could be helpful but had potential to expose students to lower complexity patients. Practice points Remote consulting confers unique educational benefits. Remote consulting can help develop history-taking and communication skills, as well as clinical reasoning skills. The psychological safety of the student and the supervisory risk of the tutor can be impacted by remote consulting, but frequent debriefs between the student and tutor can help mitigate this risk. Learning how to conduct remote, and face-to-face consultations is important in medical education. [ABSTRACT FROM AUTHOR]

Clinical reasoning is a vital medical education skill, yet its nuances in undergraduate primary care settings remain debated. This systematic review explores clinical reasoning teaching and learning intricacies within primary care. We redefine clinical reasoning as dynamically assimilating and prioritising synthesised patient, significant other, or healthcare professional information for diagnoses or non-diagnoses. This focused meta-synthesis applies transformative learning theory to primary care clinical reasoning education. A comprehensive analysis of 29 selected studies encompassing various designs made insights into clinical reasoning learning dimensions visible. Primary care placements in varying duration and settings foster diverse instructional methods like bedside teaching, clinical consultations, simulated clinics, virtual case libraries, and more. This review highlights the interplay between disease-oriented and patient-centred orientations in clinical reasoning learning. Transformative learning theory provides an innovative lens, revealing stages of initiation, persistence, time and space, and competence and confidence in students' clinical reasoning evolution. Clinical teachers guide this transformation, adopting roles as fortifiers, connoisseurs, mediators, and monitors. Patient engagement spans passive to active involvement, co-constructing clinical reasoning. The review underscores theoretical underpinnings' significance in shaping clinical reasoning pedagogy, advocating broader diversity. Intentional student guidance amid primary care complexities is vital. Utilising transformative learning, interventions bridging cognitive boundaries enhance meaningful clinical reasoning learning experiences. This study contributes insights for refining pedagogy, encouraging diverse research, and fostering holistic clinical reasoning development. [ABSTRACT FROM AUTHOR]

Background:: The NHS is struggling with GP recruitment. The Health Education England (HEE) Wass Report (By Choice not by Chance), among its recommendations to boost GP numbers, highlighted undergraduate (UG) GP placement experience as an important influence on future career choice. Aim: To explore the UG influences on GP career choice. Methods:: Two junior doctors produced a pragmatic rapid appraisal of the literature on the UG influences on GP career choice for the Wass Report. The search strategy was supported by librarians and focused on rapidly accessing and summarising relevant literature. Databases searched, including Medline, EMBASE, HMIC & grey literature, revealed 294 items. Data extraction and synthesis was pragmatic. Results:: The international evidence suggests that UG GP experience can positively influence students towards a primary care career. Longitudinal placements are more influential than traditional blocks. UK literature is limited, but there are consistencies with the international evidence. The relevant studies identified are observational with risk of bias, but this is unavoidable within this research context. Discussion:: The implications of these results for medical school curricula are discussed with particular reference to Government plans to expand medical student numbers and establish new medical schools with explicit aims to produce more GPs. [ABSTRACT FROM AUTHOR]

GP educationalists are crucial in training the future medical workforce and in developing and advancing the field of primary care medical education, yet opportunities in the UK are patchy and varied. In this article, a group of GP educationalists summarise the challenges facing the sustainability of this particular group of clinical academics and outline opportunities available at each career stage, from medical students through to senior GP educationalists. Recommendations to support the growth of this workforce include the development of a nationally recognised framework for GP educationalist careers, collaboration with professional and educational bodies and taking steps to level out opportunities in order to reduce existing inequity. [ABSTRACT FROM AUTHOR]

Interprofessional learning (IPL), involving various professions within healthcare, has been proven to improve the quality of patient care by encouraging collaboration between professionals. Careful consideration of appropriate educational tools and content is required in order to facilitate the effective IPL. This study aimed to explore medical and pharmacy students' preconceptions of the role of virtual patients (VPs) as a learning tool for IPL within their education. A secondary aim was to elicit feedback to inform the development of new VP cases. Two focus groups (one with medical students and the other with pharmacy students), consisting of six students in each, were recruited. Participant perceptions regarding VP-based IPL were explored. Data were analysed using a thematic approach. Participants thought that there were some potential learning benefits of using VPs as part of their curriculum. Pharmacy students held increased value in VPs due to their limited access to patients during their education. Medical students challenged the role of VPs in their clinical development and concerned that VPs lack the flexibility required by doctors to use their judgement and work with uncertainty. Limited understanding of team members' roles in patient care and self-reported ignorance of the overlap in curricula appear to be key barriers for students in valuing the knowledge base of each other's profession and possible benefits of using VPs in joint learning. This study generated a number of key implications which need to be considered when introducing VP-based IPL. [ABSTRACT FROM AUTHOR]

Background: Chronic pain services in the United Kingdom are required to provide services which meet the diverse needs of patients, but little is known about the access and use of these services by Minority Ethnic groups. This protocol describes a scoping review that aims to assess whether adults who access secondary and tertiary chronic pain services are representative of the UK population. Methods: A scoping review will be conducted, comprising comprehensive searches of the literature using EMBASE, MEDLINE and CINAHL databases, and grey literature for records that address the study aims. Studies that meet the eligibility criteria will report on: (i) access to chronic pain services in secondary and/or tertiary care in the United Kingdom, (ii) by adults and, (iii) state the ethnicity of the involved participants within the demographics. Both qualitative and quantitative methodologies will be included to draw broad conclusions of what the cumulative evidence says on this topic. Publication dates are limited to between 2004 and 2021 as demographic data from studies published during this period best represent the UK population recorded in the 2011 UK census. The screening and selection process will be conducted by four reviewers and data will be extracted by one reviewer. A descriptive synthesis of the extracted data will be performed. Discussion: This scoping review will be among the first to explore whether the current adult population of those with chronic pain who are accessing chronic pain services in secondary and/or tertiary care across the United Kingdom are representative of the UK Minority Ethnic population. [ABSTRACT FROM AUTHOR]

In low-risk myelodysplastic syndrome (LR-MDS), erythropoietin (EPO) is widely used for the treatment of chronic anemia. However, initial response to EPO has time-limited effects. Luspatercept reduces red blood cell transfusion dependence in LR-MDS patients. Here, we investigated the molecular action of luspatercept (RAP-536) in an in vitro model of erythroid differentiation of MDS, and also in a in vivo PDX murine model with primary samples of MDS patients carrying or not SF3B1 mutation. In our in vitro model, RAP-536 promotes erythroid proliferation by increasing the number of cycling cells without any impact on apoptosis rates. RAP-536 promoted late erythroid precursor maturation while decreasing intracellular reactive oxygen species level. RNA sequencing of erythroid progenitors obtained under RAP-536 treatment showed an enrichment of genes implicated in positive regulation of response to oxidative stress and erythroid differentiation. In our PDX model, RAP-536 induces a higher hemoglobin level. RAP-536 did not modify variant allele frequencies in vitro and did not have any effect against leukemic burden in our PDX model. These results suggest that RAP-536 promotes in vivo and in vitro erythroid cell differentiation by decreasing ROS level without any remarkable impact on iron homeostasis and on mutated allele burden. [ABSTRACT FROM AUTHOR]

Background: Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression is accurate in ruling out myelodyplastic syndromes (MDS) but might not be suitable for implementation in busy clinical laboratories. We aimed to simplify the original gating strategy and examine its accuracy. Methods: Using the individual data from 62 consecutive participants enrolled in a prospective validation study, we assessed the agreement in intra-individual robust coefficient of variation (RCV) of peripheral blood neutrophil myeloperoxidase expression and compared diagnostic accuracy between the simplified and original gating strategies. Results: Cytomorphological evaluation of bone marrow aspirate confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%), and was uninterpretable in 7 patients (11%). Median intra-individual RCV for simplified and original gating strategies were 30.7% (range, 24.7–54.4) and 30.6% (range, 24.7–54.1), with intra-class correlation coefficient quantifying absolute agreement equal to 1.00 (95% confidence interval [CI], 0.99 to 1.00). The areas under the receiver operating characteristic (ROC) curves were 0.93 (95% CI, 0.82–0.98) and 0.92 (95% CI, 0.82–0.98), respectively (P =.32). Using simplified or original gating strategy, intra-individual RCV values lower than a pre-specified threshold of 30.0% ruled out MDS for 35% (19 of 55) patients, with both sensitivity and negative predictive value estimates of 100%. Conclusions: The simplified gating strategy performs as well as the original one for ruling out MDS and has the potential to save time and reduce resource utilization. Yet, prospective validation of the simplified gating strategy is warranted before its adoption in routine. Trial registration: ClinicalTrials.gov Identifier: NCT03363399 (First posted on December 6, 2017). [ABSTRACT FROM AUTHOR]

Medical schools may find it difficult to coordinate GP practices to support undergraduate medical education in primary care. In England, every Integrated Care System area now has a funded training hub to plan and upskill the primary care and community health workforce. We evaluated whether a training hub could help deliver undergraduate medical education, co-facilitated by patient educators. No published research has evaluated this model before. We used before and after surveys (617 students), interviews (28) and focus groups (20 people) with undergraduate medical students, patient educators and training hub and medical school team members. It was feasible for a training hub to develop and co-deliver a workshop with patient educators. 61% of Year 4 undergraduate students (first clinical year) took part, a high attendance rate during the COVID-19 pandemic. 80% of students said they learnt a lot about managing conditions in primary care and the community as a result. They particularly valued engaging with patient educators and seeing interprofessional working between GPs and pharmacists, which were cornerstones of the training hub approach. The hub was able to recruit and retain patient educators more effectively than the medical school alone. Patient educators said they felt valued and developed new skills. Working with training hubs may be part of the solution to issues medical schools face when organising undergraduate education about primary care. This small evaluation suggests that this model could be tested further. [ABSTRACT FROM AUTHOR]

Background: Meta-research studies investigating methods, systems, and processes designed to improve the efficiency of systematic review workflows can contribute to building an evidence base that can help to increase value and reduce waste in research. This study demonstrates the use of an economic evaluation framework to compare the costs and effects of four variant approaches to identifying eligible studies for consideration in systematic reviews. Methods: A cost-effectiveness analysis was conducted using a basic decision-analytic model, to compare the relative efficiency of 'safety first', 'double screening', 'single screening' and 'single screening with text mining' approaches in the title-abstract screening stage of a 'case study' systematic review about undergraduate medical education in UK general practice settings. Incremental cost-effectiveness ratios (ICERs) were calculated as the 'incremental cost per citation 'saved' from inappropriate exclusion' from the review. Resource use and effect parameters were estimated based on retrospective analysis of 'review process' meta-data curated alongside the 'case study' review, in conjunction with retrospective simulation studies to model the integrated use of text mining. Unit cost parameters were estimated based on the 'case study' review's project budget. A base case analysis was conducted, with deterministic sensitivity analyses to investigate the impact of variations in values of key parameters. Results: Use of 'single screening with text mining' would have resulted in title-abstract screening workload reductions (base case analysis) of >60 % compared with other approaches. Across modelled scenarios, the 'safety first' approach was, consistently, equally effective and less costly than conventional 'double screening'. Compared with 'single screening with text mining', estimated ICERs for the two non-dominated approaches (base case analyses) ranged from £1975 ('single screening' without a 'provisionally included' code) to £4427 ('safety first' with a 'provisionally included' code) per citation 'saved'. Patterns of results were consistent between base case and sensitivity analyses. Conclusions: Alternatives to the conventional 'double screening' approach, integrating text mining, warrant further consideration as potentially more efficient approaches to identifying eligible studies for systematic reviews. Comparable economic evaluations conducted using other systematic review datasets are needed to determine the generalisability of these findings and to build an evidence base to inform guidance for review authors. [ABSTRACT FROM AUTHOR]

In order to improve the outcome observed with azacitidine (AZA) in higher‐risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA‐PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher‐risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA‐LEN And AZA‐IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy‐related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA. [ABSTRACT FROM AUTHOR]

Background: MDS‐RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD). Study design and methods: We performed a retrospective "real‐life" observational study of 6 months in 100 MDS‐RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion‐dependent MDS‐RS patients. Results: 79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p = 0.0078), more frequent iron chelation (82% vs. 50%, p = 0.0052) and higher serum ferritin (p = 0.03). During the 6‐month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6‐month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient. Discussion: MDS‐RS represents the archetypal type of chronically transfused lower‐risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS‐RS patients. [ABSTRACT FROM AUTHOR]

Context Person‐centeredness is a stated aim for medical education; however, studies suggest this is not being achieved. There is a gap in our understanding of how, why and in what circumstances medical education interventions that aim to develop person‐centredness are successful. Methods: A realist review was conducted with a search of Medline, Embase, HMIC and ERIC databases and the grey literature using the terms 'medical education' and 'person‐centred' and related synonyms. Studies that involved a planned educational intervention in medical education with data on outcomes related to person‐centredness were included. The analysis focused on how and why different educational strategies interact with biomedical learner perspectives to trigger mechanisms that may or may not lead to a change in perspective towards person‐centredness. Results: Sixty‐one papers representing fifty‐three interventions were included in the final synthesis. Nine context–intervention–mechanism–outcome configuration (CIMOc) statements generated from the data synthesis make up our refined programme theory. Where educational interventions focused on communication skills learning or experiences without person‐centred theory, learners experienced dissonance with their biomedical perspective which they resolved by minimising the importance of the learning, resulting in perspective endurance. Where educational interventions applied person‐centred theory to meaningful experiences and included support for sense making, learners understood the relevance of person‐centeredness and felt able to process their responses to learning, resulting in perspective transformation towards person‐centredness. Conclusion: Our findings offer explanations as to why communication skills‐based interventions may be insufficient to develop learners' person‐centredness. Integrating experiential person‐centred learning with theory on why person‐centredness matters to clinical practice and enabling learners to make sense of their responses to learning, may support perspective transformation towards person‐centredness. Our findings offer programme and policymakers testable theory to inform the development of medical education strategies that aim to support person‐centredness. By reviewing training strategies, the authors offer practical explanations for what does and doesn't work to support person‐centredness, arguing it is critical for us to explain why person‐centredness matters. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease was declared a pandemic in March 2020, which necessitated adaptations to medical education. This systematic review synthesises published reports of medical educational developments and innovations that pivot to online learning from workplace-based clinical learning in response to the pandemic. The objectives were to synthesise what adaptations/innovation were implemented (description), their impact (justification), and 'how' and 'why' these were selected (explanation and rationale). The authors systematically searched four online databases up to December 21, 2020. Two authors independently screened titles, abstracts and full-texts, performed data extraction, and assessed the risk of bias. Our findings are reported in alignment with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance. Fifty-five articles were included. Most were from North America (n = 40), and nearly 70% focused on undergraduate medical education (UGME). Key developments were rapid shifts from workplace-based learning to virtual spaces, including online electives, telesimulation, telehealth, radiology, and pathology image repositories, live-streaming or pre-recorded videos of surgical procedures, stepping up of medical students to support clinical services, remote adaptations for clinical visits, multidisciplinary team meetings and ward rounds. Challenges included lack of personal interactions, lack of standardised telemedicine curricula and need for faculty time, technical resources, and devices. Assessment of risk of bias revealed poor reporting of underpinning theory, resources, setting, educational methods, and content. This review highlights the response of medical educators in deploying adaptations and innovations. Whilst few are new, the complexity, concomitant use of multiple methods and the specific pragmatic choices of educators offers useful insight to clinical teachers who wish to deploy such methods within their own practice. Future works that offer more specific details to allow replication and understanding of conceptual underpinnings are likely to justify an update to this review. [ABSTRACT FROM AUTHOR]

Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. This study aimed to prospectively validate the accuracy for flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in ruling out MDS. We enrolled 62 consecutive patients who were referred for suspected MDS, based on medical history and peripheral blood cytopenia. The accuracy of intra-individual robust coefficient of variation (RCV) for peripheral blood neutrophil myeloperoxidase expression was assessed with a prespecified 30% threshold. Cytomorphological evaluation of bone marrow aspirate performed by experienced hematopathologists confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%, including 3 patients with idiopathic cytopenia of undetermined significance (ICUS)), and was uninterpretable in 7 patients (11%). The median intra-individual RCV values for neutrophil myeloperoxidase expression in peripheral blood were 37.4% (range, 30.7–54.1), 29.2% (range, 28.1–32.1), and 29.1% (range, 24.7–37.8) for patients with confirmed suspicion of MDS, ICUS, and unconfirmed suspicion of MDS, respectively (P<0.001). The area under the ROC curve was 0.92 (95% confidence interval, 0.86–0.99). An intra-individual RCV value lower than 30% ruled out MDS for 35% (i.e., 19/55) patients referred for suspected disease, with 100% sensitivity (95% CI, 85–100%) and 100% negative predictive value (95% CI, 82–100%) estimates. This study shows that flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression might obviate the need for bone marrow aspirate for 35% of patients with suspected MDS. Trial registration: ClinicalTrials.gov identifier: NCT03363399 (first posted on December 6, 2017) [ABSTRACT FROM AUTHOR]

COVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19; however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. The authors followed the five stages of a scoping review outlined by Arskey and O'Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. One hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n = 58), simulation (n = 24), assessment (n = 11), well-being (n = 8), telehealth (n = 5), clinical service reconfigurations (n = 4), interviews (n = 4), service provision (n = 2), faculty development (n = 2) and other (n = 9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). This scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease (COVID-19) was declared a pandemic in March 2020. This rapid systematic review synthesised published reports of medical educational developments in response to the pandemic, considering descriptions of interventions, evaluation data and lessons learned. The authors systematically searched four online databases and hand searched MedEdPublish up to 24 May 2020. Two authors independently screened titles, abstracts and full texts, performed data extraction and assessed risk of bias for included articles. Discrepancies were resolved by a third author. A descriptive synthesis and outcomes were reported. Forty-nine articles were included. The majority were from North America, Asia and Europe. Sixteen studies described Kirkpatrick's outcomes, with one study describing levels 1–3. A few papers were of exceptional quality, though the risk of bias framework generally revealed capricious reporting of underpinning theory, resources, setting, educational methods, and content. Key developments were pivoting educational delivery from classroom-based learning to virtual spaces, replacing clinical placement based learning with alternate approaches, and supporting direct patient contact with mitigated risk. Training for treating patients with COVID-19, service reconfiguration, assessment, well-being, faculty development, and admissions were all addressed, with the latter categories receiving the least attention. This review highlights several areas of educational response in the immediate aftermath of the COVID-19 pandemic and identifies a few articles of exceptional quality that can serve as models for future developments and educational reporting. There was often a lack of practical detail to support the educational community in enactment of novel interventions, as well as limited evaluation data. However, the range of options deployed offers much guidance for the medical education community moving forward and there was an indication that outcome data and greater detail will be reported in the future. [ABSTRACT FROM AUTHOR]

Background: Social prescribing is a way of addressing the 'non-medical' needs (e.g. loneliness, debt, housing problems) that can affect people's health and well-being. Connector schemes (e.g. delivered by care navigators or link workers) have become a key component to social prescribing's delivery. Those in this role support patients by either (a) signposting them to relevant local assets (e.g. groups, organisations, charities, activities, events) or (b) taking time to assist them in identifying and prioritising their 'non-medical' needs and connecting them to relevant local assets. To understand how such connector schemes work, for whom, why and in what circumstances, we conducted a realist review.Method: A search of electronic databases was supplemented with Google alerts and reference checking to locate grey literature. In addition, we sent a Freedom of Information request to all Clinical Commissioning Groups in England to identify any further evaluations of social prescribing connector schemes. Included studies were from the UK and focused on connector schemes for adult patients (18+ years) related to primary care.Results: Our searches resulted in 118 included documents, from which data were extracted to produce context-mechanism-outcome configurations (CMOCs). These CMOCs underpinned our emerging programme theory that centred on the essential role of 'buy-in' and connections. This was refined further by turning to existing theories on (a) social capital and (b) patient activation.Conclusion: Our realist review highlights how connector roles, especially link workers, represent a vehicle for accruing social capital (e.g. trust, sense of belonging, practical support). We propose that this then gives patients the confidence, motivation, connections, knowledge and skills to manage their own well-being, thereby reducing their reliance on GPs. We also emphasise within the programme theory situations that could result in unintended consequences (e.g. increased demand on GPs). [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) produced in hematopoietic stem cells (HSCs) are involved in the balance between quiescence, self-renewal, proliferation and differentiation processes. However the role of NOX enzymes on the early stages of hematopoietic differentiation is poorly investigated. For that, we used induced pluripotent stem cells (iPSCs) derived from X-linked Chronic Granulomatous Disease (X0CGD) patients with deficiency in NOX2, and AR220CGD patients with deficiency in p22 phox subunit which decreases NOX1, NOX2, NOX3 and NOX4 activities. CD34+ hematopoietic progenitors were obtained after 7, 10 and 13 days of iPS/OP9 co-culture differentiation system. Neither NOX expression nor activity was found in Wild-type (WT), X0CGD and AR220CGD iPSCs. Although NOX2 and NOX4 mRNA were found in WT, X0CGD and AR220CGD iPSC-derived CD34+ cells at day 10 and 13 of differentiation, NOX4 protein was the only NOX enzyme expressed in these cells. A NADPH oxidase activity was measured in WT and X0CGD iPSC-derived CD34+ cells but not in AR220CGD iPSC-derived CD34+ cells because of the absence of p22 phox , which is essential for the NOX4 activity. The absence of NOX4 activity and the poor NOX-independent ROS production in AR220CGD iPSC-derived CD34+ cells favored the CD34+ cells production but lowered their hematopoietic potential compared to WT and X0CGD iPSC-derived CD34+ cells. In addition we found a large production of primitive AR220CGD iPSC-derived progenitors at day 7 compared to the WT and X0CGD cell types. In conclusion NOX4 is the major NOX enzyme involved in the early stages of hematopoietic differentiation from iPSCs and its activity can modulate the production, the hematopoietic potential and the phenotype of iPSC-derived CD34+. Image 1 • iPS/OP9 co-culture reproduces the in vitro ROS-driven maturation of CD34+ progenitors. • Essential role of NOX4 in ROS production during the early stage of hematopoietic differentiation. • NOX4 can modulate the amount of CD34+ production, their hematopoietic potential and phenotype. • No difference in hematopoietic differentiation between control iPSCs and NOX2-deficient iPSCs. [ABSTRACT FROM AUTHOR]

Lors des transfusions de CGR le produit contient, outre Les globules rouges et la solution de conservation anticoagulante, des débris cellulaires, des protéines et des vésicules extracellulaires (EV) moins caractérisées. La libération d'EV est un mécanisme de communication intercellulaire qui focalise beaucoup de questions, en particulier dans le contexte de l'hématopoïèse des pathologies hématologiques dont les leucémies. Le receveur est donc exposé à ces EV présentes dans les CGR. Dans ce contexte, nous souhaitons évaluer la quantité d'EV dans les concentrés de globules rouges au cours du stockage. En Europe, il y a principalement deux procédés de production des CGR, avec filtration/déleucocytation AVANT la séparation au moyen d'un filtre qui retient les plaquettes et les leucocytes (on obtient un CGR et une poche de plasma) ou bien APRES la séparation ce qui permet de récupérer aussi les plaquettes pour produire les mélanges de concentrés plaquettaires. Analyse Les échantillons de CGR sont prélevés dans les tubulures en fin de transfusion, après le filtre de 200 μm pour obtenir le vrai produit transfusé sans les dépôts de fibrine ou amas de cellules mortes et avant le clamp de réglage de débit (la pompe péristaltique) pour éviter le retour de sang du receveur. Le plasma est récupéré par haute centrifugation pour retirer le culot de cellules, l'opération est répétée. Nous réalisons actuellement l'analyse des EV par mesure Nanoparticle Tracking Analysis (NTA, Malvern NanoSight). Ce travail déterminera si l'un des procédés est associé à davantage d'EV susceptibles de véhiculer des informations biologiques au receveur. [ABSTRACT FROM AUTHOR]

Abstract Waiting times in Accident and Emergency (A&E) Departments are a key performance indicator for the UK National Health Service (NHS) and are linked to medical decision making. We use the concept of medical disposal to consider the ways in which patients' medical problems are remoulded and transformed into a solvable problem enabling what he refers to as 'medical disposal'. Drawing on a study of 16 video-recorded cases from a single A&E Department in the UK, collected in 2014 and 2015, conversation analysis is used to explore how options for disposal (referral and discharge) are constructed and received in interactions between junior doctors and consultants. We consider the potential impact of information imbalances between junior doctors and consultants, as well as orientation to organisation goals in the form of standardised procedures and guidelines and constraints on time. In this way we demonstrate the interactional delicacy of discussions between junior doctors and consultants concerning moving patients on from A&E. We show how when juniors discuss cases with consultants the resultant decision making may be viewed as co-constructed. We make a case for detailed and nuanced understanding of interactions in A&E departments in order to understand the complexity of decision-making in this highly politically visible setting. Highlights • Emergency medicine (A&E) in the UK is a politically complex setting. • Discussions between junior doctors and consultants in A&E are interactionally delicate. • Decision making between junior doctors and consultants is co-constructed. • Conflicting concerns between junior doctor's need to learn and maintenance of service. [ABSTRACT FROM AUTHOR]

Summary: Isolated trisomy 8 (+8) is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDS), but its characteristics are poorly reported. We performed a retrospective study of 138 MDS patients with isolated +8, classified or reclassified as MDS (excluding MDS/myeloproliferative neoplasm). Myeloproliferative (MP) features were defined by the repeated presence of one of the following: white blood cell count >10 × 109/l, myelemia (presence of circulating immature granulocytes with a predominance of more mature forms) >2%, palpable splenomegaly. Fifty‐four patients (39·1%) had MP features: 28 at diagnosis, 26 were acquired during evolution. MP forms had more EZH2 (33·3% vs. 12·0% in non‐MP, P = 0·047), ASXL1 (66·7% vs. 42·3%, P = 0·048) and STAG2 mutations (77·8% vs. 21·7%, P = 0·006). Median event‐free survival (EFS) and overall survival (OS) were 25 and 27 months for patients with MP features at diagnosis, versus 28 (P = 0·15) and 39 months (P = 0·085) for those without MP features, respectively. Among the 57 patients who received hypomethylating agent (HMA), OS was lower in MP cases (13 months vs. 23 months in non‐MP cases, P = 0.02). In conclusion, MP features are frequent in MDS with isolated +8. MP forms had more EZH2, ASXL1 and STAG2 mutations, responded poorly to HMA, and tended to have poorer survival than non‐MP forms. [ABSTRACT FROM AUTHOR]

Summary: Treatment with azacitidine (AZA) has been suggested to be of benefit for higher‐risk myelodysplastic syndrome (HR‐MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR‐MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time‐varying variable in multivariable analysis. A Cox Regression model with time‐interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non‐CK) and International Prognostic Scoring System risk (high versus intermediate‐2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P < 0·001 at 1 year, 0·7 P = 0·019 at 2 years; 0·73 P = 0·029 at 3 years). This benefit was present in all chromosome 7 categories, but tended to be greater in patients with CK (risk reduction of 82%, 68% and 53% at 1, 3 and 6 months in CK patients; 79% at 1 month in non‐CK patients, P < 0·05 for all). AZA also significantly improved progression‐free survival (P < 0·01). This study confirms a time‐dependent benefit of AZA on outcome in patients with HR‐MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. [ABSTRACT FROM AUTHOR]