Sex and age effects on risk of non-traumatic subarachnoid hemorrhage: Retrospective cohort study of 124,234 cases using electronic health records.

OBJECTIVES: The epidemiology of non-traumatic subarachnoid hemorrhage (SAH) is unclear. This study describes the antecedent characteristics of SAH patients, compares the risk of SAH between women and men, and explores if this changes with age. MATERIALS AND METHODS: Retrospective cohort study using an electronic health records network based in the USA (TriNetX). All patients aged 18-90y with at least one healthcare visit were included. Antecedent characteristics of SAH patients (ICD-10 code I60) were measured. The incidence proportion and the relative risk between women and men, were estimated overall, in the 55-90y age group, and in five-year age categories. RESULTS: Of 58.9 million eligible patients, with 190.8 million person-years of observations, 124,234 (0.21%; 63,467 female, 60,671 male) had a first SAH, with a mean age of 56.8 (S.D. 16.8) y (women: 58.2 [16.2] y, men 55.3 [17.2] y). 9,758 SAH cases (7.8%) occurred in people aged 18-30y. Prior to the SAH, an intracranial aneurysm had been diagnosed in 4.1% (women: 5.8% men: 2.5%), hypertension in 25.1% and nicotine dependence in 9.1%. Overall, women had a lower risk of SAH compared to men (RR 0.83, 95% CI 0.83-0.84), with a progressive increase in risk ratio across age groups: from RR 0.36 (0.35-0.37) in people aged 18-24y, to RR 1.07 (1.01-1.13) aged 85-90y. CONCLUSIONS: Men are at greater risk of SAH than women overall, driven by younger adult age groups. Women are at greater risk than men only in the over 75-year age groups. The excess of SAH in young men merits investigation.

The neuropathology of bipolar disorder: systematic review and meta-analysis.

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.

Persistent neuropathological effects 14 years following amyloid-ß immunization in Alzheimer's disease.

We performed a 15-year post-mortem neuropathological follow-up of patients in the first trial of amyloid-ß immunotherapy for Alzheimer's disease. Twenty-two participants of a clinical trial of active amyloid-ß42 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-ß 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-ß 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.

Simulated virtual on-call training programme for improving non-specialised junior doctors' confidence in out-of-hours psychiatry: quantitative assessment.

AIMS AND METHOD: To investigate whether a psychiatry-specific virtual on-call training programme improved confidence of junior trainees in key areas of psychiatry practice. The programme comprised one 90 min lecture and a 2 h simulated on-call shift where participants were bleeped to complete a series of common on-call tasks, delivered via Microsoft Teams. RESULTS: Thirty-eight trainees attended the lecture, with a significant improvement in confidence in performing seclusion reviews (P = 0.001), prescribing psychiatric medications for acute presentations (P < 0.001), working in section 136 suites (places of safety) (P = 0.001) and feeling prepared for psychiatric on-call shifts (P = 0.002). Respondents reported that a virtual on-call practical session would be useful for their training (median score of 7, interquartile range 5-7.75). Eighteen participants completed the virtual on-call session, with significant improvement in 9 out of the 10 tested domains (P < 0.001). CLINICAL IMPLICATIONS: The programme can be conducted virtually, with low resource requirements. We believe it can improve trainee well-being, patient safety, the delivery of training and induction of rotating junior doctors during the COVID-19 pandemic and it supports the development and delivery of practical training in psychiatry.

Multiple-Choice versus Open-Ended Questions in Advanced Clinical Neuroanatomy: Using a National Neuroanatomy Assessment to Investigate Variability in Performance Using Different Question Types.

Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK. Prior to 2017, the competition asked open-ended questions (OEQ) in the anatomy spotter examination, and in subsequent years also asked single best answer (SBA) questions. The aim of this study is to assess medical students' performance on, and perception of, SBA and OEQ methods of assessment in a spotter style anatomy examination. Student examination performance was compared between OEQ (2013-2016) and SBA (2017-2020) for overall score and each neuroanatomical subtopic. Additionally, a questionnaire explored students' perceptions of SBAs. A total of 631 students attended the NUNC in the studied period. The average mark was significantly higher in SBAs compared to OEQs (60.6% vs. 43.1%, P < 0.0001)-this was true for all neuroanatomical subtopics except the cerebellum. Students felt that they performed better on SBA than OEQs, and diencephalon was felt to be the most difficult neuroanatomical subtopic (n = 38, 34.8%). Students perceived SBA questions to be easier than OEQs and performed significantly better on them in a neuroanatomical spotter examination. Further work is needed to ascertain whether this result is replicable throughout anatomy education.

The Career Impact of the National Undergraduate Neuroanatomy Competition.

BACKGROUND: Neurosurgery is a notoriously difficult career to enter and requires medical students to engage in extracurricular activities to demonstrate their commitment to the specialty. The National Undergraduate Neuroanatomy Competition (NUNC) was established in 2013 as a means for students to display this commitment as well as academic ability. METHODS: A bespoke 22-item questionnaire was designed to determine career outcomes and the role of competition attendance in job applications. It was distributed using the SurveyMonkey website to the 87 attendees at the 2013 and 2014 competitions. RESULTS: Responses were received by 40 competitors (response rate, 46.0%). Twenty-four responders (60.0%) intended to pursue a career in either neurosurgery (n = 18) or neurology (n = 6). This included 10 responders (25.0%) who had successfully entered either neurosurgery (n = 9) or neurology (n = 1). The performance of these 10 was significantly better than the other responders (57.0 ± 13.6% vs. 46.5 ± 13.5% [n = 30]; P = 0.036). Seventeen responders (42.5%) either included their attendance at NUNC in a post-Foundation job application or intend to. CONCLUSIONS: The NUNC provides the opportunity for medical students to demonstrate their interest in neurosurgery. It has the potential to be used as a tool for recognizing medical students suitable for neurosurgery training.

The Efficacy of Frontline Near-Peer Teaching in a Modern Medical Curriculum.

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.

Which Dopamine Polymorphisms Are Functional? Systematic Review and Meta-analysis of COMT, DAT, DBH, DDC, DRD1-5, MAOA, MAOB, TH, VMAT1, and VMAT2.

BACKGROUND: Many polymorphisms in dopamine genes are reported to affect cognitive, imaging, or clinical phenotypes. It is often inferred or assumed that such associations are causal, mediated by a direct effect of the polymorphism on the gene product itself. However, the supporting evidence is not always clear. METHODS: We conducted systematic reviews and meta-analyses to assess the empirical evidence for functional polymorphisms in genes encoding dopaminergic enzymes (COMT, DBH, DDC, MAOA, MAOB, and TH), dopamine receptors (DRD1, DRD2, DRD3, DRD4, and DRD5), the dopamine transporter (DAT), and vesicular transporters (VMAT1 and VMAT2). We defined functionality as an effect of the polymorphism on the expression, abundance, activity, or affinity of the gene product. RESULTS: We screened 22,728 articles and identified 255 eligible studies. We found robust and medium to large effects for polymorphisms in 4 genes. For catechol-O-methyltransferase (COMT), the Val158Met polymorphism (rs4680) markedly affected enzyme activity, protein abundance, and protein stability. Dopamine ß-hydroxylase (DBH) activity was associated with rs1611115, rs2519152, and the DBH-STR polymorphism. Monoamine oxidase A (MAOA) activity was associated with a 5' VNTR polymorphism. Dopamine D2 receptor (DRD2) binding was influenced by the Taq1A (rs1800497) polymorphism, and rs1076560 affected DRD2 splicing. CONCLUSIONS: Some widely studied dopaminergic polymorphisms clearly and substantially affect the abundance or activity of the encoded gene product. However, for other polymorphisms, evidence of such an association is negative, inconclusive, or lacking. These findings are relevant when selecting polymorphisms as "markers" of dopamine function, and for interpreting the biological plausibility of associations between these polymorphisms and aspects of brain function or dysfunction.

When a Child Needs a Transplant but Lacks Familial Social Support.

We present the case of a 19-month-old boy with complex congenital heart disease. His single father is skeptical of traditional medicine and does not offer the social support needed to make heart transplantation successful for his son. After the father demonstrates commitment to transplant success and provides enhanced social support, doctors place the child on a Berlin Heart (a biventricular assist device) as a bridge to transplantation and list him for transplant. When the child is matched to a donor heart, the father refuses transplantation, despite that it is the child's only chance for survival. His doctors report the case to child protective services, but they decline to take protective custody. The father then changes his mind and asks that the child be put back on the waiting list for transplant. By this time, the social supports the father implemented are no longer in place. This case raises a number of issues. First, should courts order heart transplantation when doctors believe that it is in the child's best interest and parents do not consent? Second, once parents refuse a transplant, can they change their minds? Third, if there are uncertainties regarding whether the child has the social support to make transplantation successful, should the child be relisted? Finally, should a child who is not currently a transplant candidate but who may become one in the future be supported with ventricular assist devices?

The National Undergraduate Neuroanatomy Competition: Lessons Learned from Partnering with Students to Innovate Undergraduate Neuroanatomy Education.

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.

The benefits of being a near-peer teacher.

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.

Ethical Challenges Confronted When Providing Nusinersen Treatment for Spinal Muscular Atrophy.

The US Food and Drug Administration's December 2016 approval of nusinersen for the treatment of patients with all subtypes of spinal muscular atrophy ushered in a new era for patients with spinal muscular atrophy, their families, and all those involved in their care. The extreme cost of the medication and the complicated logistical requirements for administering nusinersen via lumbar puncture have created practical challenges that raise important ethical considerations. We discuss 6 challenges faced at the institutional level in the United States: cost, limited evidence, informed consent, treatment allocation, fair distribution of responsibilities, and transparency with stakeholders. These challenges must be understood to ensure that patients with spinal muscular atrophy benefit from treatment, are protected from harm, and are treated fairly.

Pediatric staff perspectives on organ donation after cardiac death in children.

OBJECTIVES: The aims of this project were to describe whether pediatric clinical staff members believe that a donation after cardiac death (DCD) program could be consistent with the mission and core values of a children's hospital and to identify what staff consider essential to the acceptability of such a program. DESIGN: Qualitative study. SETTING: Children's hospital. SUBJECTS: Pediatric clinical staff. INTERVENTIONS: Data were gathered from pediatric clinical staff during eight focus groups conducted in a children's hospital in March and April 2005. MEASUREMENTS AND MAIN RESULTS: Eighty-eight staff members participated. Six major themes emerged from qualitative analysis of the data: a) identifying children who could be candidates for DCD; b) considering the best interests of the dying child; c) approaching parents about DCD; d) preparing parents for their child's DCD; e) doing DCD well; and f) maintaining program integrity. Themes were used to construct a conceptual framework describing a model pediatric DCD program. Pediatric staff voiced numerous concerns. However, they identified "making it happen for families" who voice a desire to participate in organ donation as the primary reason for program adoption. CONCLUSIONS: This study provides a framework for understanding pediatric staff perspectives on DCD programs in children. Results suggest several possible elements that may be helpful in framing interdisciplinary dialogue and informing institutional practices in the design of a pediatric DCD program.