Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism

Table S1. Demographic and clinical features of human subjects used in this study. Figure S1. Aβ deposition in microvessels in AD patients and APPSw/0 mice. Figure S2. Biochemical analysis of Aβ42 aggregates. Figure S3. Cy3-Aβ42 cellular uptake in wild type mouse brain slices within 30 min. Figure S4. Pericyte coverages in Lrp1lox/lox and Lrp1lox/lox; Cspg4-Cre mice. Figure S5.. LRP1 and apoE suppression with siRNA. (DOCX 1454 kb

Examining medical doctors’ internship training experience and labour market transition in Kenya

Kenya has a severe shortage of doctors. Despite medical schools increasing the numbers of medical officers (MO) in training, less than half of newly qualified/registered MOs were absorbed by the public sector between 2015 and 2018. It seems timely to understand the labour market for this profession in system terms and in personal terms for doctors, especially during their labour market entry. I used a multiple-method approach including literature reviews, quantitative survey and qualitative interviews to examine doctors’ internship training experiences and labour market transition in Kenya. I found that the resources available in hospitals overall was often inadequate to support medical internship training in Kenya, especially for Level 4/district or smaller hospitals. Over half reported that their hospitals did not have enough consultants, physical resources and supplies of diagnostics, equipment and medications required for their study and work. Over half of the interns experienced burnout and anxiety, some did not have good supervision at all times and had to perform inappropriate tasks, especially in smaller hospitals. Such poor internship experiences influenced MOs’ career intentions. Some preferred to leave the public sector, however the majority still preferred to work in the public sector or continue with specialist training immediately after internship. Nonetheless, as decentralisation in 2013 led to county governments being responsible for local workforce recruitment, they are not absorbing these MOs into the public sector. This is for reasons including limited health system financing, a willingness to rely on interns to provide hospital care, and preference for recruiting other cheaper health worker cadres. These findings suggest that Kenya needs to take a strategic approach to match the demand and supply of physicians, especially at labour market entry (i.e. internship) as well as improve the internship training resources and capacity. Poor planning and management not only wastes resources and undermines healthcare delivery, but can also be detrimental to individual physicians

Conducting cross-cultural, multi-lingual or multi-country scale development and validation in health care research: a 10-step framework based on a scoping review

Background: Valid, reliable and cross-cultural equivalent scales and measurement instruments that enable comparisons across diverse populations in different countries are important for global health research and practice. We developed a 10-step framework through a scoping review of the common strategies and techniques used for scale development and validation in a cross-cultural, multi-lingual, or multi-country setting, especially in health care research. Methods: We searched MEDLINE, Embase, and PsycINFO for peer-reviewed studies that collected data from two or more countries or in two or more languages at any stages of scale development or validation and published between 2010–22. We categorised the techniques into three commonly used scale development and validation stages (item generation, scale development, and scale evaluation) as well as during the translation stage. We described the most commonly used techniques at each stage. Results: We identified 141 studies that were included in the analysis. We summarised 14 common techniques and strategies, including focus groups or interviews with diverse target populations, and involvement of measurement experts and linguists for item content validity expert panel at the item generation stage; back-and-forth translation, collaborative team approach for the translation stage; cognitive interviews and different recruitment strategies and incentives in different settings for scale development stage; and three approaches for measurement invariance (multigroup confirmatory factor analysis, differential item functioning and multiple indicator multiple causes) for scale evaluation stage. Conclusions: We provided a 10-step framework for cross-cultural, multi-lingual or multi-country scale development and validation based on these techniques and strategies. More research and synthesis are needed to make scale development more culturally competent and enable scale application to better meet local health and development needs

Longitudinal tracking of healthcare professionals: a methodological scoping review

Background: Tracking and understanding the progress and experiences of health workers and the outcomes of workforce decisions are essential for evidence-based workforce planning. In this scoping review, we aim to identify longitudinal studies that prospectively tracked healthcare professionals and that specifically focused on workforce issues such as career preferences, choices, and working conditions, and summarise the different approaches and methods used for tracking. Methods: We searched MEDLINE, Embase, Global Health, PsycINFO, CINAHL, Education Resource Information Center (ERIC), EconLit and the Cochrane Library for articles published between 2000–2022 that longitudinally tracked doctors, nurses, midwives, physician associates/assistants. We further compared articles and conducted a back-and-forward citation search to identify longitudinal tracking studies which sometimes have multiple published articles. We developed a typology of the different tracking approaches, and summarised the major areas assessed and tracked by different studies. Results: We identified and analysed 263 longitudinal tracking studies. Based on population recruitment and follow-up methods, we grouped studies into seven categories (cohort studies, multiple-cohort studies, baseline and data linkage studies, baseline and short repeated measure studies, baseline-only studies, data linkage-only studies and repeated survey studies). The majority of studies included used a cohort or multiple-cohort design (n = 180), and several others also used data linkage (n = 45) and repeated measure approaches (n = 24). Sixty-two studies recruited participants while they were students and followed them until they became the active workforce, and nearly half of the included studies started directly from the active workforce stage. Most of the included studies examined workforce issues including employment status, preference or intention (to leave/remain/migrate, specific speciality or location etc.), and work environment, however there was a lack of widely used measurement tools for workforce issues. Additionally, nearly 40% examined wellbeing issues and a subset (20%) examined physical health in the context of workforce-related issues. Conclusion: We described a large number of different healthcare professional longitudinal tracking studies. In order for longitudinal tracking to contribute to effective workforce planning, we recommend employing a mix of cohort and data linkage approaches to collect data across the different stages of the workforce ‘working lifespan’, and using and continuing to test standardised measurement instruments to better capture experiences related to workforce and wellbeing

Experiences of EU and non-EU internationally educated nurses and midwives in the UK: a scoping review

Background: The UK’s health and care system is increasingly dependent on international recruitment to fill workforce gaps. In 2022–2023, nearly half of new Nursing and Midwifery Council (NMC) registrants were internationally educated nurses and midwives (IENs), with most coming from non-EU countries such as India, the Philippines, and Nigeria. While European Union (EU) nurses played a substantial role in NHS recruitment during the early 2010s, Brexit and subsequent immigrant policy changes contributed to a decline in EU recruit and a shift toward non-EU sources. This shift highlights the importance of understanding the differing experiences of EU and non-EU IENs. This scoping review explores recent literature on IENs’ experiences in the UK, with attention to similarities and differences between these groups. Methods: We searched Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, EBSCOhost CINAHL, and Web of Science for peer-reviewed articles that explored the experiences of IENs in the UK between 2010-2024. Three reviewers screened articles for eligibility, and data were charted and coded thematically. Results: Thirty-three studies met inclusion criteria. We identified eight key themes: (1) migration motivation, (2) registration processes, (3) workplace adaptation, (4) deskilling and recognition, (5) discrimination, (6) job satisfaction, (7) social integration, and (8) coping and support. IENs frequently migrated in search of better professional opportunities but encountered complex processes. Many struggled to adapt to the workplace, with non-EU IENs more likely to report deskilling, limited recognition of prior experience, and visa-related restrictions. Discrimination was a persistent issue, particularly for Black and non-EU IENs, leading to poor job satisfaction and career progression. EU nurses, while previously benefitting from automatic qualification recognition, increasingly reported marginalisation following Brexit. While some IENs reported receiving good support from their employers and managers, others described inconsistent or absent support, and many relied heavily on religion or informal peer networks, especially from shared cultural or national backgrounds. Conclusion: IENs in the UK face diverse barriers spanning regulation, professional adaptation, social integration, and discrimination. These challenges vary by region of origin, particularly between EU and non-EU IENs. As international recruitment continues, tailored and sustained action is needed to improve IENs’ integration, retention, and wellbeing

'We were treated like we are nobody': a mixed-methods study of medical doctors' internship experiences in Kenya and Uganda

Objective: Medical interns are an important workforce providing first-line healthcare services in hospitals. The internship year is important for doctors as they transition from theoretical learning with minimal hands-on work under supervision to clinical practice roles with considerable responsibility. However, this transition is considered stressful and commonly leads to burn-out due to challenging working conditions and an ongoing need for learning and assessment, which is worse in countries with resource constraints. In this study, we provide an overview of medical doctors’ internship experiences in Kenya and Uganda. Methods: Using a convergent mixed-methods approach, we collected data from a survey of 854 medical interns and junior doctors and semistructured interviews with 54 junior doctors and 14 consultants. Data collection and analysis were guided by major themes identified from a previous global scoping review (well-being, educational environment and working environment and condition), using descriptive analysis and thematic analysis respectively for quantitative and qualitative data. Findings: Most medical interns are satisfied with their job but many reported suffering from stress, depression and burn-out, and working unreasonable hours due to staff shortages. They are also being affected by the challenging working environment characterised by a lack of adequate resources and a poor safety climate. Although the survey data suggested that most interns were satisfied with the supervision received, interviews revealed nuances where many interns faced challenging scenarios, for example, poor supervision, insufficient support due to consultants not being available or being ‘treated like we are nobody’. Conclusion: We highlight challenges experienced by Kenyan and Ugandan medical interns spanning from burn-out, stress, challenging working environment, inadequate support and poor quality of supervision. We recommend that regulators, educators and hospital administrators should improve the resource availability and capacity of internship hospitals, prioritise individual doctors’ well-being and provide standardised supervision, support systems and conducive learning environments

Public perception of the physician associate profession in the UK: a systematic review

Background: The physician associate (PA) role within the NHS is currently under scrutiny due to recent legislative changes and concerns about their scope of practice within primary and secondary healthcare. There is currently limited knowledge of public understanding of PAs and their levels of satisfaction with PAs. This review synthesises the evidence relating to patients’ and potential patients’ understanding of and satisfaction with the PA profession in the UK. Methods: We systematically searched Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCOhost CINAHL, Education Resources Information Centre (ERIC), ProQuest Dissertations and Theses Global, and Scopus databases for empirical studies of patient understanding of PAs or satisfaction with PAs. We included quantitative, qualitative, and mixed-methods studies looking at PAs in primary and/or secondary care. Quality appraisal was conducted using the CASP Critical Appraisal checklists. A reflexive thematic analysis was used to synthesise data and the GRADE-CERqual method was used to assess the certainty of the themes. Results: A total of 18 papers involving 15 studies were included in the review. Findings revealed that patients had limited understanding of the PA role with many mistaking PAs for doctors and other healthcare professionals. Patients were confused by the lack of PA prescribing rights. There was receptivity to learn more about the PA role. The evidence suggests that patients had a largely positive view of PAs after an encounter, despite their lack of knowledge about the role. Many patients expressed a willingness to be seen by PAs in future and viewed them as a useful part of the wider healthcare system. Conclusion: In the UK, there is limited information about, and understanding of, the PA role. Nevertheless, patients were largely satisfied with the quality of care they receive from PAs during consultations. Our findings suggest a need for comprehensive public information regarding the roles and scope of practice of PA’s, and to provide the public and patients with clear expectations of their relative strengths and limitations. Further research might determine if these findings are specific to PAs, or reflect wider issues affecting public perception of other cadres of healthcare professionals

Factors influencing the development, recruitment, integration, retention and career development of advanced practice providers in hospital health care teams: a scoping review

Background: Advanced practice providers (APPs), including physician assistants/associates (PAs), nurse practitioners (NPs) and other non-physician roles, have been developed largely to meet changing healthcare demand and increasing workforce shortages. First introduced in primary care in the US, APPs are prevalent in secondary care across different specialty areas in different countries around the world. In this scoping review, we aimed to summarise the factors influencing the development, recruitment, integration, retention and career development of APP roles in hospital health care teams. Methods: We conducted a scoping review and searched Ovid MEDLINE, Ovid Embase, Ovid Global Health, Ovid PsycINFO and EBSCOhost CINAHL to obtain relevant articles published between Jan 2000 and Apr 2023 that focused on workforce management of APP roles in secondary care. Articles were screened by two reviewers independently. Data from included articles were charted and coded iteratively to summarise factors influencing APP development, recruitment, integration, retention and career development across different health system structural levels (macro-, meso- and micro-level). Results: We identified and analysed 273 articles that originated mostly from high-income countries, e.g. the US (n = 115) and the UK (n = 52), and primarily focused on NP (n = 183) and PA (n = 41). At the macro-level, broader workforce supply, national/regional workforce policies such as work-hour restrictions on physicians, APP scope of practice regulations, and views of external collaborators, stakeholders and public representation of APPs influenced organisations’ decisions on developing and managing APP roles. At the meso-level, organisational and departmental characteristics, organisational planning, strategy and policy, availability of resources, local experiences and evidence as well as views and perceptions of local organisational leaders, champions and other departments influenced all stages of APP role management. Lastly at the micro-level, individual APPs’ backgrounds and characteristics, clinical team members’ perceptions, understanding and relationship with APP roles, and patient perceptions and preferences also influenced how APPs are developed, integrated and retained. Conclusions: We summarised a wide range of factors influencing APP role development and management in secondary care teams. We highlighted the importance for organisations to develop context-specific workforce solutions and strategies with long-term investment, significant resource input and transparent processes to tackle evolving healthcare challenges

Development assistance for human resources for health, 1990–2020

Background: Investing in the health workforce is key to achieving the health-related Sustainable Development Goals. However, achieving these Goals requires addressing a projected global shortage of 18 million health workers (mostly in low- and middle-income countries). Within that context, in 2016, the World Health Assembly adopted the WHO Global Strategy on Human Resources for Health: Workforce 2030. In the Strategy, the role of official development assistance to support the health workforce is an area of interest. The objective of this study is to examine progress on implementing the Global Strategy by updating previous analyses that estimated and examined official development assistance targeted towards human resources for health. Methods: We leveraged data from IHME’s Development Assistance for Health database, COVID development assistance database and the OECD’s Creditor Reporting System online database. We utilized an updated keyword list to identify the relevant human resources for health-related activities from the project databases. When possible, we also estimated the fraction of human resources for health projects that considered and/or focused on gender as a key factor. We described trends, examined changes in the availability of human resources for health-related development assistance since the adoption of the Global Strategy and compared disease burden and availability of donor resources. Results: Since 2016, development assistance for human resources for health has increased with a slight dip in 2019. In 2020, fueled by the onset of the COVID-19 pandemic, it reached an all-time high of USD 4.1 billion, more than double its value in 2016 and a 116.5% increase over 2019. The highest share (42.4%) of support for human resources for health-related activities has been directed towards training. Since the adoption of the Global Strategy, donor resources for health workforce-related activities have on average increased by 13.3% compared to 16.0% from 2000 through 2015. For 47 countries identified by the WHO as having severe workforce shortages, the availability of donor resources remains modest. Conclusions: Since 2016, donor support for health workforce-related activities has increased. However, there are lingering concerns related to the short-term nature of activities that donor funding supports and its viability for creating sustainable health systems

Characterising Kenyan hospitals' suitability for medical officer internship training: a secondary data analysis of a cross-sectional study

Objective To characterise the capacity of Kenya internship hospitals to understand whether they are suitable to provide internship training for medical doctors. Design A secondary data analysis of a cross-sectional health facility assessment (Kenya Harmonized Health Facility Assessment (KHFA) 2018). Setting and population We analysed 61 out of all 74 Kenyan hospitals that provide internship training for medical doctors. Outcome measures Comparing against the minimum requirement outlined in the national guidelines for medical officer interns, we filtered and identified 166 indicators from the KHFA survey questionnaire and grouped them into 12 domains. An overall capacity index was calculated as the mean of 12 domain-specific scores for each facility. Results The average overall capacity index is 69% (95% CI 66% to 72%) for all internship training centres. Hospitals have moderate capacity (over 60%) for most of the general domains, although there is huge variation between hospitals and only 29 out of 61 hospitals have five or more specialists assigned, employed, seconded or part-time-as required by the national guideline. Quality and safety score was low across all hospitals with an average score of 40%. As for major specialties, all hospitals have good capacity for surgery and obstetrics-gynaecology, while mental health was poorest in comparison. Level 5 and 6 facilities (provincial and national hospitals) have higher capacity scores in all domains when compared with level 4 hospitals (equivalent to district hospitals). Conclusion Major gaps exist in staffing, equipment and service availability of Kenya internship hospitals. Level 4 hospitals (equivalent to district hospitals) are more likely to have a lower capacity index, leading to low quality of care, and should be reviewed and improved to provide appropriate and well-resourced training for interns and to use appropriate resources to avoid improvising