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Louise Tan, a Year 12 student from Ballyclare in County Antrim, Northern Ireland, recently attended the joint NDS and NDORMS Virtual Work Experience. In this guest blog, Louise reflects on her experience.
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Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.
OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.
Developing a Community of Scholars for Students, Residents, and Early-Career Researchers: MedEd Collaborative - A Health Professions Education Research Collaborative
Problem Students, residents, and early-career researchers (ECRs) have limited opportunities for early involvement in high-quality health professions education research (HPER). This project aimed to create a community of scholars for medical students, residents, and ECRs to increase early-career HPER collaboration. A community of scholars is a community of practice in which the common area of interest is scholarly work. This article describes how MedEd Collaborative was established as a permanent national HPER collaborative led by medical students, residents, and ECRs. Approach MedEd Collaborative was formed in September 2020, consisting of a committee of medical students, residents, and ECRs who oversee collaborators in the United Kingdom. Guidance on creating research collaboratives, developing a community of scholars, and collaborative writing was followed. The primary measurable outcome was to publish one original research article that used a collaborative research approach and incorporated theory. The community was cultivated by providing opportunities for early-career involvement in collaborative HPER projects and mentorship and training in HPER methods. Outcomes MedEd Collaborative has developed a community of scholars that increased opportunities for early involvement in high-quality HPER for 82 medical students, residents, and ECRs. The collaborative structure facilitates increasing legitimate peripheral participation in HPER: acting as a collaborator provides basic research skills development, and learners can gradually assume more responsibility as their skills progress by acting on project committees. MedEd Collaborative's research outputs progressed HPER by using conceptual frameworks to explain student volunteering decisions and experiences during the COVID-19 pandemic, and the scholarly output included 15 publications (of which 4 were original research), 19 presentations, 4 prizes, and 2 grants. Next Steps To ensure the sustainability of the collaborative, the collaborative will refine its identity in the HPER landscape, expand the model with other methods and to other professions, strengthen its collaborative structure, and establish formal partnerships.
Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins.
Ricin, produced from the castor beans of Ricinus communis, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab')2 antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD99 of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab')2, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication.
Measuring physiological stress in the common marmoset (Callithrix jacchus): Validation of a salivary cortisol collection and assay technique.
Cortisol levels are often used as a physiological measure of the stress response in captive primates, with non-invasive measures of this being an important step in welfare assessment. We report a method of collecting saliva samples voluntarily from unrestrained captive common marmosets (Callithrix jacchus), and validate an enzyme-linked immunosorbent assay (ELISA) technique previously unused in this species. Saliva samples were collected from marmosets housed in pairs in a UK laboratory. The assay showed parallelism, precision, accuracy and sensitivity, meeting the criteria typically used to investigate the effectiveness of new analytical techniques. Use of Salimetrics® Oral Swabs considerably increased the amount of cortisol recovered in comparison with previous studies using cotton buds. However, while use of banana on the swabs can encourage chewing, it may influence results. Although increases in cortisol levels have traditionally been interpreted as an indicator of stress in primates, there are many factors that affect the hypothalamic-pituitary-adrenal axis, with some studies showing decreases in cortisol levels post-stressor. Following a likely stressful event (capture for weighing), we also found cortisol levels significantly decreased, possibly due to social buffering or 'blunting' of the HPA axis. Order of weighing also had an effect. The method therefore provided an effective non-invasive means of assessing acute changes in cortisol level that may be more useful than previous methods, improving our ability to study physiological aspects of welfare in primates. We discuss methodological considerations, as well as implications of using cortisol as a measure of stress.