Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Population incidence and associated mortality of urinary tract infection in people living with dementia.

OBJECTIVES: Urinary tract infections (UTIs) frequently cause hospitalisation and death in people living with dementia (PLWD). We examine UTI incidence and associated mortality among PLWD relative to matched controls and people with diabetes and investigate whether delayed or withheld treatment further impacts mortality. METHODS: Data were extracted for n = 2,449,814 people aged ≥ 50 in Wales from 2000-2021, with groups matched by age, sex, and multimorbidity. Poisson regression was used to estimate incidences of UTI and mortality. Cox regression was used to study the effects of treatment timing. RESULTS: UTIs in dementia (HR=2.18, 95 %CI [1.88-2.53], p < .0) and diabetes (1.21[1.01-1.45], p = .035) were associated with high mortality, with the highest risk in individuals with diabetes and dementia (both) (2.83[2.40-3.34], p < .0) compared to matched individuals with neither dementia nor diabetes. 5.4 % of untreated PLWD died within 60 days of GP diagnosis-increasing to 5.9 % in PLWD with diabetes. CONCLUSIONS: Incidences of UTI and associated mortality are high in PLWD, especially in those with diabetes and dementia. Delayed treatment for UTI is further associated with high mortality.

Giant sequoia (Sequoiadendron giganteum) in the UK: carbon storage potential and growth rates.

Giant sequoias (Sequoiadendron giganteum) are some of the UK's largest trees, despite only being introduced in the mid-nineteenth century. There are an estimated half a million giant sequoias and closely related coastal redwoods (Sequoia sempervirens) in the UK. Given the recent interest in planting more trees, partly due to their carbon sequestration potential and also their undoubted public appeal, an understanding of their growth capability is important. However, little is known about their growth and carbon uptake under UK conditions. Here, we focus on S. giganteum and use three-dimensional terrestrial laser scanning to perform detailed structural measurements of 97 individuals at three sites covering a range of different conditions, to estimate aboveground biomass (AGB) and annual biomass accumulation rates. We show that UK-grown S. giganteum can sequester carbon at a rate of 85 kg yr-1, varying with climate, management and age. We develop new UK-specific allometric models for S. giganteum that fit the observed AGB with r 2 > 0.93 and bias < 2% and can be used to estimate S. giganteum biomass more generally. This study provides the first estimate of the growth and carbon sequestration of UK open-grown S. giganteum and provides a baseline for estimating their longer-term carbon sequestration capacity.

It's not special treatment That's part of the Treaty of Waitangi! Organisational barriers to enhancing the Aged Residential Care environment for older Maori and Whanau in New Zealand.

BACKGROUND: New Zealand's older Indigenous Maori people experience poorer health and reduced access to healthcare than their older non-Maori counterparts. Organisational factors (such as leadership or workforce) may influence the attitudes and perceptions of older Maori and their family (whanau) to use aged residential care services. Currently, there is a paucity of research surrounding the organisational barriers that impact the experiences of older Maori people who seek care in aged residential care (ARC) services. METHODS: This study used a Kaupapa Maori qualitative research approach that legitimises Maori knowledge and critiques structures that subjugate Maori autonomy and control over their wellbeing. Interviews regarding their experiences of care were carried out with older Maori (n = 30) and whanau (family) members (n = 18) who had used, or declined to use an aged residential care facility. Narrative data were analysed inductively for themes that illustrated organisational barriers. RESULTS: The key organisational theme was 'Culturally safe care', within which there were three barriers: 'Acceptability and Adequacy of Facility', 'Interface Between Aged Residential Care and Whanau Models of Care', and 'Workforce'. Collectively, these barriers emphasise the importance of an organisational approach to improving the quality of care delivered to older Maori and whanau in ARC. CONCLUSION: Fostering a collective culture of equity within ARC provider services and equipping healthcare leaders and staff with the skills and knowledge to deliver culturally safe care is critical to addressing organisational barriers to ARC.

Using MCQ response certainty to determine how aspects of self-monitoring develop through a medical course.

INTRODUCTION: Self-monitoring of clinical-decision-making is essential for health care professional practice. Using certainty in responses to assessment items could allow self-monitoring of clinical-decision-making by medical students to be tracked over time. This research introduces how aspects of insightfulness, safety and efficiency could be based on certainty in, and correctness of, multiple-choice question (MCQ) responses. We also show how these measures change over time. METHODS: With each answer on twice yearly MCQ progress tests, medical students provided their certainty of correctness. An insightful student would be more likely to be correct for those answers given with increasing certainty. A safe student would be expected to have a high probability of being correct for answers given with a high certainty. An efficient student would be expected to have a sufficiently low probability of being correct when they have no certainty. The system was developed using first principles and data from one cohort of students. A dataset from a second cohort was then used as an independent validation sample. RESULTS: The patterns of aspects of self-monitoring were similar for both cohorts. Almost all the students met the criteria for insightfulness on all tests. Most students had an undetermined outcome for the safety aspect. When a definitive result for safety was obtained, absence of safety was most prevalent in the middle of the course, while the presence of safety increased later. Most of the students met the criteria for efficiency, with the highest prevalence mid-course, but efficiency was more likely to be absent later. DISCUSSION: Throughout the course, students showed reassuring levels of insightfulness. The results suggest that students may balance safety with efficiency. This may be explained by students learning the positive implications of decisions before the negative implications, making them initially more efficient, but later being more cautious and safer.

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative.

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Cross-cultural code-switching - the impact on international medical graduates in New Zealand.

BACKGROUND: New Zealand relies on International Medical Graduates (IMGs); however, the retention of IMGs is not optimal. This research uses a lens of cross-cultural code-switching to explore how professional and cultural differences impact on International Medical Graduates' (IMGs') journeys to practise effectively and remain in New Zealand. METHODS: Utilising theory-informing inductive analysis within a constructivist approach, framework analysis was conducted following 14 face-to-face interviews with IMGs. The analysis then explored the degree to which their experiences could be explained by cross-cultural code-switching's psychological challenges (authenticity, competence, and resentment). RESULTS: Analysis showed there was an expectation for IMGs to code-switch. The greater the cultural and professional difference of IMGs (compared to New Zealand), the greater the intensity of psychological challenges experienced when switching. Moreover, IMGs received minimal support, making it difficult to overcome psychological challenges, especially the competence challenge. This led to feelings of frustration and vulnerability. Code-switching could also explain why complaints about IMGs were more likely when IMGs were stressed or tired. CONCLUSION: Cross-cultural code-switching can be used to explain and identify how cultural differences cause psychological challenges. These findings inform how programmes can better support IMGs in orientation and ongoing training. Additionally, establishing, and allocating IMG cultural mentors would assist in addressing IMGs' vulnerability and isolation. With this support, the journey may prove more manageable and encourage IMGs to continue practising in their adopted country.

Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.

BACKGROUND: Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic. METHODS: In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021. FINDINGS: Of 3 106 690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57 396 people (35 148 [61·2%] women and 22 248 [38·8%] men) met inclusion criteria for this study and contributed 101 428 person-years of follow-up. Of the 57 396 people with dementia, 11 929 (20·8%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10 000 person-months in March, 2019, to 1305 per 10 000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17·1%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death. INTERPRETATION: During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required. FUNDING: British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.

Informed consent for medical student involvement in patient care: an updated consensus statement.

Enabling patients to consent to or decline involvement of medical students in their care is an essential aspect of ethically sound, patient-centred, mana-enhancing healthcare. It is required by Aotearoa New Zealand law and Te Kaunihera Rata o Aotearoa Medical Council of New Zealand policy. This requirement was affirmed and explored in a 2015 Consensus Statement jointly authored by the Auckland and Otago Medical Schools. Student reporting through published studies, reflective assignments and anecdotal experiences of students and teachers indicate procedures for obtaining patient consent to student involvement in care remain substandard at times. Between 2020 and 2023 senior leaders of Aotearoa New Zealand's two medical schools, and faculty involved with teaching ethics and professionalism, met to discuss these challenges and reflect on ways they could be addressed. Key stakeholders were engaged to inform proposed responses. This updated consensus statement is the result. It does not establish new standards but outlines Aotearoa New Zealand's existing cultural, ethical, legal and regulatory requirements, and considers how these may be reasonably and feasibly met using some examples.

Sample representativeness and influence of attrition on longitudinal data collected as part of a national medical career tracking project.

BACKGROUND: The Medical Schools Outcomes Database and Longitudinal Tracking Project (MSOD) in New Zealand is one example of a national survey-based resource of medical student experiences and career outcomes. Longitudinal studies of medical students are valuable for evaluating the outcomes of medical programs against workforce objectives. As a prospective longitudinal multiple-cohort study, survey response rates at each collection point of MSOD vary. This paper assesses the effects of participant non-response rates on MSOD data. METHODS: Demographic variables of MSOD respondents between 2012 and 2018 were compared to the distribution of the demographic variables in the population of all NZ medical graduates to ascertain whether respondent samples at multiple survey collection points were representative of the population. Analysis using logistic regression assessed the impact of participant non-response on variables at collection points throughout MSOD. RESULTS: 2874 out of a total population of 2939 domestic medical students graduating between 2012 and 2018 responded to MSOD surveys. Entry and exit surveys achieved response rates around 80% and were broadly representative of the total population on demographic variables. Post-graduation survey response rates were around 50% of the total population of graduates and underrepresented graduates from the University of Auckland. Between the entry and exit and the exit and postgraduation year three samples, there was a significant impact of non-response on ascribed variables, including age at graduation, university, gender and ethnic identity. Between the exit and postgraduation year one sample, non-response significantly impacted ascribed and non-ascribed variables, including future practice intentions. CONCLUSION: Samples collected from MSOD at entry and exit are representative, and findings from cross-sectional studies using these datasets are likely generalisable to the wider population of NZ medical graduates. Samples collected one and three years post-graduation are less representative. Researchers should be aware of this bias when utilizing these data. When using MSOD data in a longitudinal manner, e.g. comparing the change in career intentions from one collection point to the next, researchers should appropriately control for bias due to non-response between collection points. This study highlights the value of longitudinal career-tracking studies for answering questions relevant to medical education and workforce development.

Identifying dementia using medical data linkage in a longitudinal cohort study: Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a longitudinal study of ageing with well-characterised assessments, but until now, it has relied on self-report or proxies for dementia such as cognitive tests. Our aims were twofold: a) to describe a framework for identifying dementia in a cohort study. b) to report the age-specific incidence and prevalence of all-cause dementia and dementia subtypes in 865 individuals in the LBC1936. METHODS: Electronic Health Records (EHR) of all participants were reviewed, and relevant information was extracted to form case vignettes for everyone with any record of cognitive dysfunction. The EHR data sources include hospital and clinic letters, general practitioner and hospital referrals, prescribed medications, imaging and laboratory results. Death certificate data were obtained separately. Clinician assessments were performed when there was concern about a participant's cognition. A diagnosis of probable dementia, possible dementia, or no dementia was agreed upon by a consensus diagnostic review board, comprised of a multidisciplinary team of clinical dementia experts who reviewed case vignettes and clinician assessment letters. For those with probable dementia, a subtype was also determined, where possible. We compared the agreement between our newly ascertained dementia diagnoses with the existing self-reported dementia diagnoses. RESULTS: Self-reported dementia diagnoses were positive in only 17.8% of ascertained dementia diagnoses. The EHR review identified 163/865 (18.8%) individuals as having cognitive dysfunction. At the consensus diagnostic review board, 118/163 were diagnosed with probable all-cause dementia, a prevalence of 13.6%. Age-specific dementia prevalence increased with age from 0.8% (65-74.9 years) to 9.93% (85-89.9 years). Prevalence rates for women were higher in nearly all age groups. The most common subtype was dementia due to Alzheimer disease (49.2%), followed by mixed Alzheimer and cerebrovascular disease (17.0%), dementia of unknown or unspecified cause (16.1%), and dementia due to vascular disease (8.5%). CONCLUSIONS: We present a robust systematic framework and guide for other cohort teams wanting to ascertain dementia diagnoses. The newly ascertained dementia diagnosis provides vital data for further analyses of LBC1936 to allow exploration of lifecourse predictors of dementia.

The consequences of cultural difference: the international medical graduate journey in New Zealand.

Objectives: To identify how differences in cultural and professional values between New Zealand born and trained doctors and International Medical Graduates (IMGs) affect the practice and retention of IMGs in New Zealand. Methods: A mixed-method approach was used. An anonymous 42-item online questionnaire was used to compare participants' cultural and professional values. Participants were 373 New Zealand doctors, 198 IMG, and 25 doctors born and raised elsewhere but who qualified in New Zealand, a group not identified prospectively. The qualitative component used interviews with 14 IMGs to identify cultural challenges faced and with nine New Zealand doctors to identify the challenges they faced working alongside IMGs. Qualitative data were transcribed and analysed thematically. Results: There were differences in power distance, with the medically qualified in New Zealand doctors having the highest power distance, followed by the IMGs, suggesting a preference for a hierarchical environment at odds with the New Zealand culture. Interviews found cultural differences in communication styles and hierarchy contributed to professional challenges. The cultural transition was difficult for IMGs as they received minimal support. One-third of IMGs acknowledged their behaviours did not fit well in New Zealand. Complaints about IMGs increased when they reverted to default behaviours regarded negatively by New Zealand colleagues or patients. Conclusions: IMGs are open to change but face a lack of orientation and cultural education opportunities, hindering integration. Residency programs must recognise this disconnect and incorporate cross-cultural programmes in the curriculum. Such programmes would assist the adaption and retention of IMG doctors.

Supporting Bystanders and Other Staff Exposed to Negative Workplace Behaviour: Developing and Testing the IMO Intervention Framework in the Clinical Workplace.

Background: Medical student and health-care staff bullying remain international concerns. Our understanding about what might solve such problems is still developing. A common approach suggested for bystanders to bullying is that they challenge or "stand up" to the bully. At the same time, the considerable risks should they act (eg, verbal rebuke) are rarely acknowledged, and neither is the potential for considerable cognitive dissonance should they choose not to. Methods: Drawing on a substantial literature review, we developed an interventional program, initially with medical student bullying in mind, that generally employed a discourse for values cultivation. We implemented and evaluated this program through 6 cycles of action research methodology in 6 different departments of one tertiary teaching hospital. Data include individual interviews, discussions with key participants plus freehand comments from wider staff's workshop evaluations. Results: Alongside others, an early serendipitous finding was the "IMO" [Indirect, focus on Me, focus on Outcome] framework, intended for bystanders to student bullying. From using this framework, participants reported developing confidence in tackling negative behaviours, that interactions had better outcomes and that the workplace atmosphere felt more relaxed. It's use also significantly reduced cognitive dissonance. Encouragingly, participants went on to use IMO for staff-staff bullying incidents, and other common negative behaviours. We attribute IMO's utility to its memorability, simplicity and for catering to the many possible causes of bullying, including values issues, without perpetuating or creating conflict. Conclusion: The IMO framework is offered as a widely usable framework for all staff in a clinical environment - a useful addition to popular frameworks used in the clinical workplace, ideas from which might also help these be further refined. Further evaluation would establish whether IMO invites long-term change and its utility in other contexts.

Educators as Judges: Applying Judicial Decision-Making Principles to High-Stakes Education Assessment Decisions.

Phenomenon: Programmatic assessment and competency-based education have highlighted the need to make robust high-stakes assessment decisions on learner performance from evidence of varying types and quality. Without guidance, lengthy deliberations by decision makers and competence committees can end inconclusively with unresolved concerns. These decisional dilemmas are heightened by their potential impacts. For learners, erroneous decisions may lead to an unjustified exit from a long-desired career, or premature promotion to clinical responsibilities. For educators, there is the risk of wrongful decision-making, leading to successful appeals and mistrust. For communities, ill-prepared graduates risk the quality and safety of care. Approaches such as psychometric analyses are limited when decision-makers are faced with seemingly contradictory qualitative and quantitative evidence about the same individual. Expertise in using such evidence to make fair and defensible decisions is well established in judicial practice but is yet to be practically applied to assessment decision-making. Approach: Through interdisciplinary exchange, we investigated medical education and judicial perspectives on decision-making to explore whether principles of decision-making in law could be applied to educational assessment decision-making. Using Dialogic Inquiry, an iterative process of scholarly and mutual critique, we contrasted assessment decision making in medical education with judicial practice to identify key principles in judicial decision-making relevant to educational assessment decisions. We developed vignettes about common but problematic high-stakes decision-making scenarios to test how these principles could apply. Findings: Over 14 sessions, we identified, described, and applied four principles for fair, reasonable, and transparent assessment decision-making. These were: The person whose interests are affected has a right to know the case against them, and to be heard.Reasons for the decision should be given.Rules should be transparent and consistently applied.Like cases should be treated alike and unlike cases treated differently.Reflecting our dialogic process, we report findings by separately presenting the medical educator and judicial perspectives, followed by a synthesis describing a preferred approach to decision-making in three vignettes. Insights: Judicial principles remind educators to consider both sides of arguments, to be consistent, and to demonstrate transparency when making assessment decisions. Dialogic Inquiry is a useful approach for generating interdisciplinary insights on challenges in medical education by critiquing difference (e.g., the meaning of objectivity) and achieving synthesis where possible (e.g., fairness is not equal treatment of all cases). Our principles and exemplars provide groundwork for promoting good practice and furthering assessment research toward fairer and more robust decisions that will assist learning.

Medical students and informed consent-response to "Consent for Teaching".

Nil.

Four ways to get a grip on making robust decisions from workplace-based assessments.

Synthesising the results of workplace-based assessments to inform robust decisions is seen as both important and difficult. Concerns about failing to fail the trainee not ready to proceed has drawn disproportionate attention to assessors. This paper proposes a model for a more systems-based view so that the value of the assessor's judgement is incorporated while preserving the value and robustness of collective decision-making. Our experience has shown it can facilitate robust decisions on some of the more difficult areas, such as professionalism.

Il est aussi important que difficile de synthétiser les résultats d'évaluations en milieu de travail pour fonder des décisions solides. Les préoccupations liées à la renonciation à faire échouer les stagiaires qui ne sont pas prêts à poursuivre leur formation ont focalisé l'attention sur les évaluateurs, et ce de manière disproportionnée. Cet article propose un modèle avec une vision plus systémique permettant d'intégrer la valeur du jugement de l'évaluateur tout en préservant la valeur et la solidité de la prise de décision collective. Notre expérience a montré qu'il peut faciliter la prise de décisions robustes en ce qui concerne des domaines plus difficiles comme le professionnalisme.

Systematic Review of Cerebral Phenotypes Associated With Monogenic Cerebral Small-Vessel Disease.

Background Cerebral small-vessel disease (cSVD) is an important cause of stroke and vascular dementia. Most cases are multifactorial, but an emerging minority have a monogenic cause. While NOTCH3 is the best-known gene, several others have been reported. We aimed to summarize the cerebral phenotypes associated with these more recent cSVD genes. Methods and Results We performed a systematic review (PROSPERO [International Prospective Register of Systematic Reviews]: CRD42020196720), searching Medline/Embase (conception to July 2020) for any language publications describing COL4A1/2, TREX1, HTRA1, ADA2, or CTSA pathogenic variant carriers. We extracted data about individuals' characteristics and clinical and vascular radiological cerebral phenotypes. We summarized phenotype frequencies per gene, comparing patterns across genes. We screened 6485 publications including 402, and extracted data on 390 individuals with COL4A1, 123 with TREX1, 44 with HTRA1 homozygous, 41 with COL4A2, 346 with ADA2, 82 with HTRA1 heterozygous, and 14 with CTSA. Mean age ranged from 15 (ADA2) to 59 years (HTRA1 heterozygotes). Clinical phenotype frequencies varied widely: stroke, 9% (TREX1) to 52% (HTRA1 heterozygotes); cognitive features, 0% (ADA2) to 64% (HTRA1 homozygotes); and psychiatric features, 0% (COL4A2; ADA2) to 57% (CTSA). Among individuals with neuroimaging, vascular radiological phenotypes appeared common, ranging from 62% (ADA2) to 100% (HTRA1 homozygotes; CTSA). White matter lesions were the most common pathology, except in ADA2 and COL4A2 cases, where ischemic and hemorrhagic lesions dominated, respectively. Conclusions There appear to be differences in cerebral manifestations across cSVD genes. Vascular radiological changes were more common than clinical neurological phenotypes, and present in the majority of individuals with reported neuroimaging. However, these results may be affected by age and biases inherent to case reports. In the future, better characterization of associated phenotypes, as well as insights from population-based studies, should improve our understanding of monogenic cSVD to inform genetic testing, guide clinical management, and help unravel underlying disease mechanisms.

Learning is what happens between seeing patients: defining clinical access.

The inability to access clinical placements during the COVID-19 pandemic stimulated us to reflect on key elements of the experience, beyond history taking and examination. We were also mindful of concerns about work readiness of new graduates. We identified seven aspects of clinical experience distinct from those requiring direct patient contact. These are: recognise and contribute to the collective competence of multidisciplinary teams; apply project management principles to the complexities of clinical care; integrate personal and team-based clinical reasoning; deliver patient-centred collaborative care; achieve an integrated perspective of clinical care; demonstrate adaptability to health systems; consolidate professional identity formation. We consider that making these aspects explicit in learning objectives and assessments in medical schools is likely to improve the work-readiness of new graduates and should also be reflected in accreditation standards.