Charlotte H. Harrison

Background Early warning systems (EWS) used across the world typically assign a fixed number of points to patients receiving supplemental oxygen, regardless of amount. This ordinal binary approach may fail to recognise deteriorating patients who have an increasing oxygen requirement with otherwise stable observations. It is unclear whether weighting oxygen beyond binary scoring improves recognition of deterioration. Aims We aimed to describe all general adult EWS that grade oxygen beyond binary scoring (part 1). Where reported, we summarised the performance of graded oxygen EWS in comparison to binary scoring (part 2). Methods We systematically reviewed the literature, searching Embase, MEDLINE, CINAHL, Cochrane Central and Web of Science. We included studies of vital-sign-only EWS, for adult inpatients, which included grades of oxygen therapy above binary weighting (‘graded oxygen weighting’). We summarised methods of including graded oxygen therapy. We performed a random-effects meta-analysis of the effects of graded oxygen weighting inclusion in comparison to binary weighting. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool. Results 15 studies reported the development of 16 EWS with graded oxygen weighting, classified by flow rate, delivery device and/or fraction of inspired oxygen. Four studies compared graded oxygen EWS to binary oxygen EWS. Meta-analysis showed a significant improvement in the performance of graded oxygen EWS over binary oxygen EWS (logit(AUROC)=0.19; 95% CI 0.094 to 0.285; p=0.002). 15/16 models were at high risk of bias. Conclusions 16 EWS with graded oxygen weighting were identified. Graded oxygen models had improved recognition of deterioration. Future work should explore the optimal method of oxygen classification and how this could be integrated into future EWS. PROSPERO registration number CRD42024443362.

Introduction The novel coronavirus SARS-CoV2 and the associated disease, Covid-19, continue to pose a global health threat. The CovidCalculatorUK is an open-source online tool (covidcalculatoruk.org) that estimates the probability that an individual patient, who presents to a UK hospital, will later test positive for SARS-CoV2. The objective is to aid cohorting decisions and minimise nosocomial transmission of SARS-CoV2. Methods This n = 500 prospective, observational, multicentre, validation study compared the CovidCalculatorUK’s estimated probability of Covid-19 with the first SARS-CoV2 oropharyngeal/nasopharyngeal swab result for individual patients admitted to hospital during the study period (01.04.20 − 18.05.20). A comparison with senior clinicians’ estimates of the probability of Covid-19 was also made. Results Patients who were prospectively grouped, by the CovidCalculatorUK, into 0-30% estimated probability, 30-60% and 60-100% estimated probability went on to have first swab SARS-CoV2 positive results in: 15.7%, 30.5% and 61.9% of cases, respectively. CovidCalculatorUK performance demonstrated an area under the curve of 0.76 (95% CI 0.71 – 0.81) (p < 0.001). Senior clinician stratification of the estimated probability of Covid-19 performed similarly to the CovidCalculatorUK. Conclusion The CovidCalculatorUK provides a reasonably accurate estimate of the probability of an individual testing positive on their first SARS-CoV2 nasopharyngeal/oropharyngeal swab. The CovidCalculatorUK output performs similarly to a senior clinician’s estimate. Further evolution of the calculator may improve performance.

We performed a 15-year post-mortem neuropathological follow-up of patients in the first trial of amyloid-β immunotherapy for Alzheimer’s disease. Twenty-two participants of a clinical trial of active amyloid-β₄₂ immunization (AN1792, Elan Pharmaceuticals) or placebo were studied. Comprehensive post-mortem neuropathological assessments were performed from 4 months to 15 years after the trial. We analysed the relationships between the topographical distribution of amyloid-β removal from the cerebral cortex and tau pathology, cerebrovascular territories, plasma anti-AN1792 antibody titres and late cognitive status. Seventeen of 22 (77%) participants had Alzheimer’s neuropathological change, whereas 5 of 22 (23%) had alternative causes for dementia (progressive supranuclear palsy = 1, Lewy body disease = 1, vascular brain injury = 1, and frontotemporal lobar degeneration = 2). Nineteen of the 22 participants had received the active agent, three the placebo. Fourteen of 16 (88%) patients with Alzheimer’s disease receiving the active agent had evidence of plaque removal (very extensive removal = 5, intermediate = 4, very limited = 5, no removal = 2). Of particular note, two Alzheimer’s patients who died 14 years after immunization had only very sparse or no detectable plaques in all regions examined. There was a significant inverse correlation between post-vaccination peripheral blood anti-AN1792 antibody titres and post-mortem plaque scores (ρ = − 0.664, P = 0.005). Cortical foci cleared of plaques contained less tau than did cortex with remaining plaques, but the overall distribution of tangles was extensive (Braak V/VI). In conclusion, patients with Alzheimer’s disease actively immunized against amyloid-β can remain virtually plaque-free for 14 years. The extent of plaque removal is related to the immune response. This long duration of efficacy is important in support of active immunization protocols as therapy for, or potentially prevention of, neurodegeneration-associated protein accumulations. Inclusion of patients without Alzheimer’s disease in Alzheimer’s therapy trials is a problem for assessing the efficacy of treatment. Despite modification of Alzheimer’s pathology, most patients had progressed to severe dementia, notably including the five with very extensive plaque removal, possibly due to continued tau propagation. Neuropathology follow-up of patients in therapeutic trials provides valuable information on the causes of dementia and effects of treatment.

Within medical education a reduction in curriculum time for subjects, such as anatomy puts pressure on educators to ensure the same learning outcomes are conveyed in less time. This has the potential to impact negatively on student experience. Near‐peer teaching (NPT) is often praised as an effective revision tool, but its use as a frontline teaching resource remains unreported. The study explores the potential for NPT to promote delivery of learning outcomes and maximize student experience within a neuroanatomy module for second year medical students. The study occurred in three educational settings, (1) frontline NPT of cranial nerves, (2) revision session NPT of cranial nerves, and (3) NPT alongside faculty staff in laboratory‐based neuroanatomy practical exercises. For the first and second components, knowledge was measured using a pre‐ and post‐session test and student perception was ascertained with a questionnaire. For the third component, student perception was assessed with an end‐of‐module survey. The results show that overall, NPT was well received by learners. A significant knowledge gain was seen between the pre‐ and post‐session test of the frontline NPT session. The study presents evidence in favor of using NPTs to supplement the delivery of learning outcomes in a time and resource constrained curriculum. In particular, for the effective delivery of frontline material. Anat Sci Educ 0: 1–9. © 2018 American Association of Anatomists.

Various neuropathological findings have been reported in bipolar disorder (BD). However, it is unclear which findings are well established. To address this gap, we carried out a systematic review of the literature. We searched over 5000 publications, identifying 103 data papers, of which 81 were eligible for inclusion. Our main findings can be summarised as follows. First, most studies have relied on a limited number of brain collections, and have used relatively small sample sizes (averaging 12 BD cases and 15 controls). Second, surprisingly few studies have attempted to replicate closely a previous one, precluding substantial meta-analyses, such that the latter were all limited to two studies each, and comprising 16–36 BD cases and 16–74 controls. As such, no neuropathological findings can be considered to have been established beyond reasonable doubt. Nevertheless, there are several replicated positive findings in BD, including decreased cortical thickness and glial density in subgenual anterior cingulate cortex, reduced neuronal density in some amygdalar nuclei, and decreased calbindin-positive neuron density in prefrontal cortex. Many other positive findings have also been reported, but with limited or contradictory evidence. As an important negative result, it can be concluded that gliosis is not a feature of BD; neither is there neuropathological evidence for an inflammatory process.

Undergraduates often perceive neuroscience to be a challenging discipline. As the scope of neuroscience continues to expand, it is important to provide undergraduates with sufficient opportunities to develop their knowledge and skills with the aim of encouraging the future generation of basic and clinical neuroscientists. Through our experience of developing the National Undergraduate Neuroanatomy Competition (NUNC), we have accrued an extensive volume of performance data and subjective insight into the delivery of undergraduate neuroanatomy education, which has the potential to inform how to better engage students within this field. More broadly, our group has implemented a technology enhanced learning platform alongside a peer-assisted teaching program. These achieve the dual purpose of compensating for the reduction in dedicated neuroanatomy teaching hours and encouraging undergraduates to develop an interest in the neurosciences. Here, we consider how improving the learning experience at an undergraduate level encourages further engagement in the neurosciences and the importance of this within the wider neuroscience community.

Summary: Background: Near‐peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored. Method: A questionnaire was distributed to the teachers involved in anatomy near‐peer teaching at the University of Southampton and Brighton and Sussex Medical School ( BSMS ). This questionnaire was designed using a rating scale of 0–10 to assess teacher perspectives on their level of knowledge, teaching skills and enjoyment of teaching. Free‐text responses determined the teachers’ motivation and perceived benefits from the teaching. Results: Twenty‐eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS . Long‐term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near‐peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near‐peer teacher in medical school Discussion: There are numerous advantages to being a near‐peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies.