Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

The identification of biomarker differences between grade I and II meningiomas: Fibulin-2 is a novel biomarker for differentiating grade II from grade I meningiomas

Background: There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas, facilitated by recent advances in meningioma genomics. WHO grade II meningiomas remain a controversial group of CNS tumours to diagnose/treat, compared to the more prevalent and extensively researched grade I tumours. Aim: To identify molecular signatures (biomarkers) unique to grade II meningiomas (versus grade I). Methods: I combined literature review with an unbiased global proteomic analysis of four grade I and four grade II primary (meningioma) cell cultures, to identify proteins differentially expressed between both grades. Validation of the significantly differentially expressed proteins was then performed by Western blotting (WB) and quantitative polymerase chain reaction (qPCR) in primary cells; via WB, immunohistochemistry and qPCR in tissue; and in plasma, via enzyme-linked immunosorbent assay (ELISA). Results: I identified 3554 proteins commonly expressed in both meningioma grades. Further analysis revealed that 86 of these were significantly-differentially up/down-regulated. Initial validation studies on some of the promising candidates have confirmed the patterns of expression between the two tumour grades. Of these 86, we discovered that the calcium binding extracellular matrix glycoprotein, Fibulin-2 was significantly differentially expressed between grade I and II meningiomas, at protein and gene expression levels. Proteomic analyses (p<0.05), Western blotting (p<0.01) and qPCR (p<0.01) confirmed significantly higher Fibulin-2 expression levels in grade II meningiomas compared to grade I. To distinguish between grade I and II meningiomas, Receiver Operating Characteristic (ROC) analysis of Fibulin-2 qPCR expression levels in meningioma tissue indicated an AUC of 0.73 (96% specificity). Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients (cut-off value >2.5ng/ml with 95% specificity). Conclusion: The findings of this study have identified novel biomolecular differences between grade I/II meningiomas that can potentially aid in the diagnosis and clinical management of grade II meningiomas. Elevated Fibulin- 2 levels is proposed as a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.Royal College of Surgeons of EnglandBrain Tumour Researc

Trends in research grant applications and outcomes among medical students in the United Kingdom: a national self-reported cross-sectional survey

Background Research funding disparities contribute to clinical academic workforce inequalities. Hence, our study explores the association between student demographics and research grant application rates and outcomes among UK medical students. Methods This is a national multicentre cross-sectional survey of UK medical students in the 2020–21 academic year. Multiple zero-inflated negative binomial regression and generalized linear model (binomial distribution; logit link) were utilized to investigate the association between student demographics, number of grant applications submitted, and successful grant applications (yes or no). P-values less than a Bonferroni-corrected significance level of 0.05/36 = 0.0014 were considered to be statistically significant. Results A total of 1528 students participated from 36 medical schools. One hundred fifty-one respondents (9.9%) had applied for research grants. Black students submitted applications 2.90 times more often than white students [Incident rate ratio (IRR): 2.90, 95% confidence interval (CI): 1.37–6.16], with no ethnic disparity in the odds of successful applications. Gender did not influence application rates significantly (P = .248), but women were 4.61 times more likely to secure a grant than men [odds ratio: 4.61, 95% CI: 2.04–10.4]. Being a PubMed-indexed author was associated with increased grant application submission rates [IRR: 3.61, 95% CI: 2.20– 5.92] while conducting more research was associated with greater odds of securing a grant [odds ratio: 1.42, 95% CI: 1.17– 1.73]. Conclusion Although black students submitted more applications, ethnicity did not influence success rates. Gender did not influence application rates, but women were more successful. These findings underscore the need for strategies supporting women and underrepresented students for continued academic achievement after graduation. Key Messages What is already known on this topic Research funding for post-PhD researchers is believed to be a major driver of gender and ethnic inequalities in the clinical academic workforce. Students who receive research grants are more likely to receive postgraduate research grants. What this study adds Black students applied for more research grants than white students, but there were no ethnic differences in the odds of securing a grant. There were no gender differences in the research grant application rates. However, female students had greater odds of securing research grants compared to male students. How this study might affect research, practice or policy Medical schools should incorporate grant writing skills into the undergraduate research curriculum. Also, to sustain women’s academic success post medical school, the NIHR and affiliates should provide research award extensions and childcare support for women when required

Predictors of self-reported research productivity amongst medical students in the United Kingdom: a national cross-sectional survey

Abstract Background The number of academic clinicians in the UK is declining and there are demographic inequalities in the clinical-academic workforce. Increased research productivity by medical students is believed to reduce future attrition in the clinical-academic workforce. Thus, this study investigated the association between student demographics and research productivity amongst UK medical students. Methods This is a national multicentre cross-sectional study of UK medical students in the 2020/21 academic year. We appointed one student representative per medical school, and they disseminated a 42-item online questionnaire over nine weeks, through departmental emails and social media advertisements. The outcome measures were: (i) publications (yes/no) (ii) number of publications (iii) number of first-authored publications (iv) abstract presentation (yes/no). We utilised multiple logistic and zero-inflated Poisson regression analyses to test for associations between the outcome measures and predictor variables at a 5% significance level. Results There are 41 medical schools in the UK. We received 1573 responses from 36 UK medical schools. We failed to recruit student representatives from three newly formed medical schools, whilst two medical schools prohibited us from sending the survey to their students. Women had lower odds of having a publication (OR: 0.53, 95% CI: 0.33–0.85) and on average had fewer first-author publications than men (IRR: 0.57, 95% CI: 0.37–0.89). Compared to white students, mixed-ethnicity students had greater odds of having a publication (OR: 3.06, 95% CI: 1.67–5.59), an abstract presentation (OR: 2.12, 95% CI: 1.37–3.26), and on average had a greater number of publications (IRR: 1.87, 95% CI: 1.02–3.43). On average, students who attended independent UK secondary schools had a higher rate of first-author publications compared to those that attended state secondary schools (IRR: 1.97, 95% CI: 1.23–3.15). Conclusion Our data suggest that there are gender, ethnic and socioeconomic inequalities in research productivity among UK medical students. To tackle this, and potentially improve diversity in clinical academia, we recommend that medical schools should facilitate targeted high quality research mentorship, funding and training, especially for under-represented-in-medicine students

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. Methods and analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. Ethics and dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media