Impact of research activity on performance of general practices: a qualitative study.

BACKGROUND: There is evidence that engaging in research is directly associated with better performance. If this relationship is to be strengthened, it is necessary to understand the mechanisms which might underlie that relationship. AIM: To explore the perspectives of staff and wider stakeholders about mechanisms by which research activity might impact on the performance of general practices. DESIGN & SETTING: Qualitative study using semi-structured interviews with general practice professionals and wider stakeholders in England. METHOD: Individual interviews with 41 purposively sampled staff in 'research ready' or 'research active' general practices and 21 other stakeholders. Interviews were independently coded by three researchers using a Framework approach. RESULTS: Participants described potential 'direct' and 'indirect' impacts on their work. 'Direct' impacts included research changing practice work (eg, additional records searches for particular conditions), bringing in additional resources (eg, access to investigations or staff) and improving relationships with patients. 'Indirect' impacts included job satisfaction (eg, perception of practice as a centre of excellence and innovation, and the variety afforded by research activity reducing burnout) and staff recruitment (increasing the attractiveness of the practice as a place to work). Respondents identified few negative impacts. CONCLUSIONS: Staff and stakeholders identified a range of potential impacts of research activity on practice performance, with impacts on their working lives most salient. Negative impacts were not generally raised. Nevertheless, respondents generally discussed potential impacts rather than providing specific examples of those impacts. This may reflect the type of research activity conducted in general practice, often led by external collaborators.

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

Integration of social determinants of health information within the primary care electronic health record: a systematic review of patient perspectives and experiences.

BACKGROUND: Social determinants of health (SDOH) are the non-medical factors that impact health. Although geographical measures of deprivation are used, individual measures of social risk could identify those most at risk and generate more personalised care and targeted referrals to community resources. We know SDOH are important to health care, but it is not yet known whether their collection via the electronic health record (EHR) is acceptable and useful from the patient perspective. AIM: To synthesise relevant literature to explore patient perspectives on integrating information about SDOH into primary care EHRs, and the opportunities and challenges of its implementation in a general practice setting. DESIGN & SETTING: Systematic review of primary care-based qualitative and mixed-method studies using thematic framework analysis. METHOD: Key databases were searched for articles reporting patient perspectives of SDOH collection within the primary care EHR. Qualitative and mixed-methods studies written in English were included. A framework analysis was conducted to identify themes. RESULTS: From 14 included studies, the following five main themes were identified: rationale for SDOH screening and the anticipated outcomes; impact of the provider-patient relationship on patient perceptions; data, which included privacy concerns; screening process and referral; and recommendations for future research. CONCLUSION: Integration of information on SDOH into the EHR appears acceptable to patients. This review has added to the discussion of whether and how to implement SDOH screening and referral programmes into UK primary care systems.

Operationalising generalism in medical education: a narrative review of international policy and mission documents.

INTRODUCTION: Despite moves across medical education to increase learning of generalist principles, a lack of clarity about what generalism means and how we should train doctors as 'generalists', has remained. This study explores how international, undergraduate and postgraduate, policy and educational mission documents characterise the practice and learning of generalism and how this can inform physician training. METHODS: A narrative literature review was conducted based on policy and mission documents identified through grey literature searches and a wider systematic review looking at empirical texts. Texts published between 1999 and present and related to 'generalism' were eligible for inclusion. Texts were coded and codes were reviewed and grouped into key themes. RESULTS: Thirty-four documents were included. Definitions vary: some described generalism as a basic skill, whilst others emphasised expertise. Factors which support learning generalism include: favourable financial outcomes; ageing populations; coordination of multidisciplinary care; demand for doctors with transferable skills; and patient expectations. Barriers to learning about generalism include: preference for specialisation; structure of undergraduate teaching and assessment; and the hidden curriculum. Solutions may include re-imagining generalists and specialists as being on a continuum as well as increasing exposure throughout medical education. DISCUSSION: Whilst generalism is consistently positioned as valuable, less clarity exists about how best to operationalise this in medical education. Fundamental ideological and structural changes within teaching curricula and assessment, are necessary to improve generalist learning and to promote sustainable practice. Medical education needs careful, considered planning to ensure workforce expertise is meeting population needs.

Access to Chronic Pain Services for Adults from Minority Ethnic Groups in the United Kingdom (UK): a Scoping Review.

BACKGROUND: Chronic pain services in the UK 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. OBJECTIVE: To assess the available evidence regarding the ethnic profile of adults who access secondary and tertiary chronic pain services in the UK. METHODS: A scoping review was conducted (August 2021-October 2021), comprising comprehensive literature searches using Embase, Medline and CINAHL databases and the grey literature. Studies were included if they reported on (i) access to chronic pain services in secondary and/or tertiary care in the UK, (ii) adults and (iii) stated the ethnicity of the involved participants. Studies were included if published between 2004 and 2021, as demographic data during this period would be broadly representative of the UK population, as per the 2021 UK census. A descriptive synthesis of the extracted data was performed. RESULTS: The search yielded 124 records after duplicates were removed. Following title and abstract screening, 44 full texts were screened, ten of which were included in the review. CONCLUSIONS: This is the first review to explore access to chronic pain services for adults from minority ethnic groups in the UK. Given the limited number of studies that met the inclusion criteria, the review highlights the need for routine collection of ethnicity data using consistent ethnic categories within UK chronic pain services and increased involvement of minority ethnic groups within chronic pain research. Findings should inform future research that aims to improve access to UK chronic pain services for adults from minority ethnic groups.

Transformative learning in clinical reasoning: a meta-synthesis in undergraduate primary care medical education.

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.

Primary care micro-teams: an international systematic review of patient and healthcare professional perspectives.

BACKGROUND: International trends have shifted to creating large general practices. There is an assumption that interdisciplinary teams will increase patient accessibility and provide more cost-effective, efficient services. Micro-teams have been proposed to mitigate for some potential challenges of practice expansion, including continuity of care. AIM: To review available literature and examine how micro-teams are described, and identify opportunities and limitations for patients and practice staff. DESIGN AND SETTING: This was an international systematic review of studies published in English. METHOD: Databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus) and grey literature were searched. Studies were included if they provided evidence about implementation of primary care micro-teams. Framework analysis was used to synthesise identified literature. The research team included a public contributor co-applicant. The authors conducted stakeholder discussions with those with and without experience of micro-team implementation. RESULTS: Of the 462 studies identified, 24 documents met the inclusion criteria. Most included empirical data from healthcare professionals, describing micro-team implementation. Results included characteristics of the literature; micro-team description; range of ways micro-teams have been implemented; reported outcomes; and experiences of patients and staff. CONCLUSION: The organisation of primary care has potential impact on the nature and quality of patient care, safety, and outcomes. This review contributes to current debate about care delivery and how this can impact on the experiences and outcomes of patients and staff. This analysis identifies several key opportunities and challenges for future research, policy, and practice.

[Creating a community of heads of department to meet hospital system challenges: First experience in haematology]. / Créer une communauté de chefs de service pour répondre aux défis du système hospitalier : première expérience en hématologie.

The French hospital system crises are constantly forcing the heads of departments to adapt and find solutions for maintaining optimal patient care in a context of staff shortage. Facing these challenges, we had the desire to create a community of department heads capable of helping each other, sharing their experiences, relying on collective intelligence and, ultimately, contributing to rebuilding their hospitals from the bottom up. In this respect, we arranged a two-day seminar, which brought together fourteen heads of hematology departments who share the same desire to challenge their organizations with a collaborative approach and make them evolve. The seminar was animated by an external speaker and included many fruitful sessions, both formal and informal. Following this seminar, participants are now interested in sharing this experience with other department heads throughout the organization of "collaborative seminars of heads of department." Such seminars would serve to create a real community of department heads capable of supporting each other to improve our organizations and to generate new ideas to participate in the reconstruction of our health system from the bottom. This approach is in line with the current strategy of public services to restore a prominent role to hospital departments. We hope that our initiative will also inspire heads of departments in other specialties.

[Treatment of lower risk myelodysplastic syndromes]. / Traitement des syndromes myélodysplasiques de bas risque.

For low-risk myelodysplastic syndromes, the goal of treatment is to correct cytopenias or their consequences. Erythropoiesis-stimulating agents have an important role in the management of anemia. In this chapter, we will detail the response to ESAs, the factors predictive of response to ESAs. However, the search for new therapeutic options for low-risk, ESA-resistant MDS remains necessary as the incidence of AML transformation of the patients is higher. We can retain luspatercept for MDS with excess ring of sideroblasts, lenalidomide, and some molecules currently being tested such as imetelstat or roxedustat. However, the search for new therapeutic options for ESA-resistant low-risk MDS remains necessary. We can use androgenotherapy or TPO agonists in limited access for symptomatic thrombocytopenia.

Developing a career as a GP educationalist: contemporary challenges and workforce solutions.

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.

Digital undergraduate medical education and patient and carer involvement: a rapid systematic review of current practice.

BACKGROUND: Involving patients and carers in medical students' learning aims to centralise the perspective of healthcare users and supports our future medical workforce in the development of key skills. Medical schools are increasingly using digital technology for teaching and it is timely to understand how to maintain patient and carer involvement in this context. METHODS: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported authentic patient or carer involvement in undergraduate medical education where technology was also used. Study quality was assessed by the Mixed Methods Appraisal Tool (MMAT). Levels of patient or carer involvement were assessed using Towle et al.'s (2010) taxonomy, from Level 1 (lowest level) to Level 6 (highest level). RESULTS: Twenty studies were included in this systematic review. In 70% of studies, patients and carers featured in video or web-based case scenarios with no interaction between healthcare users and students. The remaining 30% of studies reported real-time interactions between students and patients via remote clinical encounters. Digital teaching sessions involving patients or carers were perceived to be valuable by students and educators, and increased student engagement, patient-centred attitudes, clinical knowledge, and communication skills. No studies reported the perspective of patients or carers. DISCUSSION: Digital technology has not yet driven higher levels of patient and carer involvement in medical training. "Live" interactions between students and patients are becoming more common but challenges need addressing to ensure positive experiences for all involved. Future teaching should enhance the role of patients and carers in medical education and support them to overcome any potential barriers to doing so remotely.

[Role and interest of hepcidin in iron homeostasis]. / Rôle et intérêt du dosage de l'hepcidine dans l'homéostasie du fer.

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.

CPX-351 in higher risk myelodysplastic syndrome and chronic myelomonocytic leukaemia: a multicentre, single-arm, phase 2 study.

BACKGROUND: CPX-351, an encapsulated form of cytarabine and daunorubicin, has shown greater efficacy than the classic 3 + 7 treatment administration in secondary acute myeloid leukaemia. Given that higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia share similarities with secondary acute myeloid leukaemia, we aimed to investigate the safety and efficacy of CPX-351 in this context. METHODS: This investigator-initiated two-cohort phase 2 trial was conducted by the Groupe Francophone des Myélodysplasies, with 12 participating centres in France. It comprised cohort A (reported here and completed), which included patients in first-line treatment, and cohort B, which was stopped for lack of inclusion (ie, not enough patients met the inclusion criteria), for patients with hypomethylating agent failure that is not reported here. Cohort A enrolled patients with newly diagnosed higher-risk myelodysplastic syndrome or chronic myelomonocytic leukaemia (aged 18-70 years old) with an Eastern Cooperative Oncology Group performance status of 0-1. Intravenous CPX-351 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) was given on days 1, 3, and 5, with a second induction cycle given (same daily dose on days 1 and 3) if at least a partial response was not reached. Patients who responded could receive up to four monthly consolidation cycles (same daily dose on day 1) or allogeneic haematopoietic stem-cell transplantation (HSCT). Overall response rate after one or two induction courses according to European LeukemiaNet 2017 acute myeloid leukaemia was the primary endpoint after CPX-351 induction, whether patients received one or two induction cycles. Safety was assessed in all patients enrolled (in cohort A). This trial is registered with ClinicalTrials.gov, NCT04273802. FINDINGS: Between April 29, 2020, and Feb 10, 2021, 21 (68%) male and ten (32%) female patients were enrolled. 27 (87%) of 31 patients responded (95% CI 70-96). 16 (52%) of the 31 patients received at least one consolidation cycle. 30 (97%) of the 31 patients included were initially considered eligible for allogeneic HSCT and 29 (94%) of the 31 patients had the procedure. Median follow-up was 16·1 months (IQR 8·3-18·1). The most common grade 3-4 adverse events were pulmonary (eight [26%] of 31 patients) and cardiovascular (six [19%] of 31 patients). There were 14 serious adverse events (mainly hospitalisation for infection [n=5] and only one was treatment-related) and no treatment-related death. INTERPRETATION: CPX-351 appears to be active and safe in patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukaemia, allowing bridging to allogenic HSCT in most patients. FUNDING: Jazz Pharmaceuticals.

Students' and tutors' experiences of remote 'student-patient' consultations.

BACKGROUND: Remote consulting has become part of the medical student clinical experience in primary care, but little research exists regarding the impact on learning. AIM: To describe the experiences of General Practitioner (GP) educators and medical students in using student-led remote consultations as an educational tool. METHOD: A qualitative, explorative study conducted at four UK medical schools. GP educators and medical students were purposively sampled and interviewed. RESULTS: 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. DISCUSSION: 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.[Box: see text].

Extracellular Vesicles and MicroRNA in Myelodysplastic Syndromes.

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.

Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network.

PURPOSE: Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML). PATIENTS AND METHODS: Newly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression. RESULTS: One-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System-mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients (P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm (P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04). CONCLUSION: Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).

Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases.

BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.