East Midlands Evidence Repository (EMER)

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Welcome to the East Midlands Evidence Repository.

The East Midlands Evidence Repository (EMER) is the official institutional research repository for; Derbyshire Community Health Services, Leicester Partnership Trust, NHS Nottingham and Nottinghamshire CCG, Nottinghamshire Healthcare, Sherwood Forest Hospitals, University Hospitals of Derby and Burton and the University Hospitals Of Leicester

EMER is intended to make NHS research more visible and discoverable by capturing, storing and preserving the East Midlands research output and making it available to the research community through open access protocols.

Wherever possible, full-text content is provided for all research publications in the repository. Content grows daily as new collections are added.

 

 

  • The relationship between general practitioner movement behaviours with burnout and fatigue

    Biddle, G J H (2024-02-16)
    Background: Physical inactivity is associated with feelings of burnout and fatigue, which in turn are associated with reduced performance among healthcare practitioners. This study explored movement behaviours of general practitioners (GPs) and the association between these behaviours with burnout and fatigue. Methods: GPs in Northern Ireland were asked to wear a thigh-worn accelerometer for seven days and complete validated questionnaires to assess the association between daily number of steps, time spent sitting and standing with feelings of burnout and fatigue. Results: Valid accelerometer data were obtained from 47 (77.0%) participants. Average workday sitting time, standing time and number of steps were 10.6 h (SD 1.5), 3.8 h (SD 1.3), and 7796 steps (SD 3116) respectively. Participants were less sedentary (8.0 h (SD 1.6)) and more active (4.7 h (SD 1.4) standing time and 12,408 steps (SD 4496)) on non-workdays. Fourteen (30.4%) participants reported burnout and sixteen (34.8%) reported severe fatigue. There were no significant associations between sitting, standing and step counts with burnout or fatigue (p > 0.05). Conclusion: GPs were less active on workdays compared to non-workdays and exhibited high levels of sitting. Feelings of burnout and fatigue were highly prevalent, however movement behaviours were not found to be associated with burnout and fatigue. Given the increased sedentariness among GPs on workdays compared to non-workdays, GPs should consider how they can improve their movement behaviours on workdays to help optimise their wellbeing.
  • Participatory translational science of neurodivergence: model for attention-deficit/hyperactivity disorder and autism research

    Balwani, Beta (2024-02-16)
    Background: There are increasing calls for neurodivergent peoples' involvement in research into neurodevelopmental conditions. So far, however, this has tended to be achieved only through membership of external patient and public involvement (PPI) panels. The Regulating Emotions - Strengthening Adolescent Resilience (RE-STAR) programme is building a new participatory model of translational research that places young people with diagnoses of attention-deficit hyperactivity disorder (ADHD) and autism at the heart of the research team so that they can contribute to shaping and delivering its research plan. Aims: To outline the principles on which the RE-STAR participatory model is based and describe its practical implementation and benefits, especially concerning the central role of members of the Youth Researcher Panel (Y-RPers). Method: The model presented is a culmination of a 24-month process during which Y-RPers moved from advisors to co-researchers integrated within RE-STAR. It is shaped by the principles of co-intentionality. The account here was agreed following multiple iterative cycles of collaborative discussion between academic researchers, Y-RPers and other stakeholders. Results: Based on our collective reflections we offer general guidance on how to effectively integrate young people with diagnoses of ADHD and/or autism into the core of the translational research process. We also describe the specific theoretical, methodological and analytical benefits of Y-RPer involvement in RE-STAR. Conclusions: Although in its infancy, RE-STAR has demonstrated the model's potential to enrich translational science in a way that can change our understanding of the relationship between autism, ADHD and mental health. When appropriately adapted we believe the model can be applied to other types of neurodivergence and/or mental health conditions.
  • The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies

    Barratt, Jonathan (2024-02-01)
    Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The "four-hit hypothesis" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.
  • Pegargiminase plus first-line chemotherapy in patients with nonepithelioid pleural mesothelioma: the ATOMIC-meso randomized clinical trial

    Fennell, Dean A (2024-02-15)
    Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. Design, setting, and participants: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. Intervention: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. Main outcomes and measures: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. Results: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo). Conclusions and relevance: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.

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