Maarten F. M. Engel

Pica, the persistent ingestion of non‐nutritive, non‐food substances for ≥ 1 month at a developmentally inappropriate age, is regularly observed but understudied in sickle cell disease (SCD). Its prevalence and risk factors are unclear. This systematic review aims to estimate pica prevalence and synthesize evidence on associated characteristics and correlates in SCD. We searched Embase, MEDLINE ALL, Web of Science, Cochrane CENTRAL, PsycINFO and Google Scholar up to 31 October 2025, for studies reporting original data on the prevalence and characteristics of pica in individuals ≥ 2 years with SCD. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Meta‐analysis of prevalence used random‐effects models. Data on substances consumed were pooled. Literature on potential correlates was narratively summarized across biological, psychological and social domains. Ten studies (1585 participants) from North America ( n = 6), Africa ( n = 1), Europe ( n = 1), the Middle East ( n = 1) and South America ( n = 1) were included, with sample sizes ranging from 55 to 395. The pooled prevalence of pica was 34% (95% CI: 24%–46%, I ² = 94%). Across four studies, the most commonly ingested materials were clay/dirt ( n = 110, 39.3%), paper ( n = 60, 21.4%) and fabric ( n = 29, 10.4%). Narrative synthesis identified younger age, lower bodyweight, lower haemoglobin levels, higher impulsivity, lower socioeconomic status, lower family satisfaction and a positive family history as potential correlates of pica in SCD. Pica in SCD is highly prevalent. Psychosocial determinants may play a larger role than previously anticipated, alongside biological and disease‐related contributors. However, current evidence is limited by small sample sizes, inconsistent findings, and lack of validated assessment tools. To advance understanding of the aetiology of pica, future longitudinal studies integrating biological, psychological, social and neuroimaging measures are needed.

Introduction: Health advocacy (HA) is acknowledged as a core competence in medical education. However, varying and sometimes conflicting conceptualisations of HA exist, making it challenging to integrate the competence consistently. While this diversity highlights the need for a deeper understanding of HA conceptualisations, a comprehensive analysis across the continuum of medical education is absent in the literature. This protocol has been developed to clarify the conceptual dimensions of the HA competence in literature as applied to medical education. Methods and analysis: The review will be conducted in line with the JBI (formerly Joanna Briggs Institute) methodology for scoping reviews. A comprehensive literature search was developed and already carried out in eight academic databases and Google Scholar, without restrictions on publication date, geography or language. Articles that describe the HA role among students and physicians who receive or provide medical education will be eligible for inclusion. Two independent reviewers will independently complete title and abstract screening prior to full-text review of selected articles and data extraction on the final set. A descriptive-analytical approach will be applied for summarising the data. Ethics and dissemination: This scoping review does not involve human participants, as all evidence is sourced from publicly available databases. Therefore, ethical approval is not required for this study. The findings from this scoping review will be disseminated through submission to a high-quality peer-reviewed journal and presented at academic conferences. By clarifying the conceptualisations of HA, this review aims to contribute to a shared narrative that will strengthen the foundation for integrating the HA role into medical education. Trial registration number: A preliminary version of this protocol was registered on the Open Science Framework on 9 December 2024, and can be accessed at the following link: https://osf.io/ed2br . We have also registered our scoping review protocol as a preprint at medRxiv: https://doi.org/10.1101/2024.12.09.24318699 .

Background: Steatotic liver disease (SLD) affects ~30% of adults worldwide. The global population is continuously threatened by epidemic and endemic viral diseases. This study aims to thoroughly examine the interaction between SLD and major viral diseases. Methods: We systematically searched databases from inception to April 2, 2024, for observational studies recording viral-infected adult patients with eligible data on the presence of hepatic steatosis. Results: Six hundred thirty-six eligible studies were included in the analysis of SLD prevalence. Among patients with monoinfections, the highest SLD prevalence was observed in those infected with HCV at 49% (95% CI: 47%–51%), followed by SARS-CoV-2 (39%, 95% CI [34%–44%]), HIV (39%, 95% CI [33%–44%]), and HBV (36%, 95% CI [32%–40%]). Additionally, co-infections, such as HCV-HIV and HBV-HCV, exhibit even higher SLD prevalence. The prevalence of steatohepatitis is particularly high in HIV-infected (24%, 95% CI: 17%–30%) and HCV-infected (18%, 95% CI: 13%–24%) populations. The co-existence of SLD with viral infections was associated not only with the progression of liver disease but also with more severe outcomes of the infections and poorer responses to antiviral treatment. The combination of cardiometabolic risk factors and viral-associated and host factors contributes to the higher risk of SLD in viral-infected populations. Conclusions: SLD is highly prevalent in viral-infected populations, and the reciprocal interactions between SLD and viral diseases exacerbate both conditions, leading to poorer patient outcomes in general.

Background: In adolescents and young adults (AYAs) with cancer, the importance of patient-centered research outcomes is increasingly acknowledged and there is a need for consensus on the most relevant outcomes. This review provides a comprehensive overview of outcomes relevant to AYAs with cancer in order to develop an AYA-specific core outcome set (COS) as part of the European project STRONG-AYA. Methods: A literature search was conducted to identify relevant articles in five databases. Each article was reviewed by two independent researchers, using Rayyan (an online tool) to screen articles by their title/abstract and then by their full text. Subsequently, the data were extracted using a predefined, tailored extraction framework. Results: In total, 17,301 articles were screened, of which 1631 were included in the analyses. Registry studies (52.9%) were the most used study type. Well-represented continents were North America (50.3%) and Europe (27.8%). Of the five core areas, functioning (47.0%) and epidemiology (44.9%) were covered most often, followed by physiological/clinical (42.4%), resource use (6.1%), and adverse events (4.5%). The outcome domains that were represented the most include mortality/survival (43.1%), delivery of care (23.4%), outcomes relating to neoplasms (22.7%), and emotional functioning/well-being (19.2%). Conclusions: This literature review provides a foundation for the development of an AYA-specific COS for improving the relevance and efficiency of measuring outcomes, the pooling of (international) research data, and the value of care for current and future AYAs with cancer. Finalization and refinement of the COS should be a priority for future research.

Introduction: Health Advocacy (HA) is acknowledged as a core competence in medical education. However, varying and sometimes conflicting conceptualizations of HA exists, making it challenging to integrate the competence consistently. While this diversity highlight the need for a deeper understanding of HA conceptualizations, a comprehensive analysis across the continuum of medical education is absent in the literature. This protocol has been developed to clarify the conceptual dimensions of the HA competence in literature as applied to medical education. Methods and analysis: The review will be conducted in line with the JBI methodology for scoping reviews. A comprehensive literature search was developed and already carried out in eight academic databases and Google Scholar, without restrictions on publication date, geography or language. Articles that describe the HA role among students and physicians that receive or provide medical education will be eligible for inclusion. Two independent reviewers will independently complete title and abstract screening, prior to full-text review of selected articles and data extraction on the final set. A descriptive-analytical approach will be applied for summarizing the data. Ethics and dissemination: This scoping review does not involve human participants, as all evidence is sourced from publicly available databases. Therefore, ethical approval is not required for this study. The findings from this scoping review will be disseminated through submission to a high-quality peer-reviewed journal and presented at academic conferences. By clarifying the conceptualizations of HA, this review aims to contribute to a shared narrative that will strengthen the foundation for integrating the HA role into medical education. Trial registration number: A preliminary version of this protocol was registered on the Open Science Framework (OSF) on 9 December 2024, and can be accessed at the following link: osf.io/6f94y. Article Summary: Strengths and limitations of this study: ⇒ This review will maintain consistency and meet the quality standards established by other scoping reviews by adhering to the JBI methodology for scoping reviews and following to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension checklist specifically designed for scoping reviews (PRISMA-ScR). ⇒ Two independent reviewers will conduct the title and abstract screening, full text screening and data extraction, including pilot exercises, to enhance the systematic rigor of the screening process and increase the reliability of the results. ⇒ The search strategy is systematically developed in collaboration with a medical librarian, who also serves as a co-author on this project. ⇒ This review ensures inclusivity by avoiding language restrictions, designing data visualizations for colorblind readers, and committing to open-access resources to align with FAIR (findable, accessible, interoperable and reusable) principles. ⇒ This review aims to pave the way toward a shared understanding of the health advocacy competence in medical education. However, while it contributes valuable insights to the discourse, it does not possess the capacity to inform policy or practice changes in the field.

Objectives The aim of this systematic review was to provide an overview of value-based healthcare (VBHC) strategies and/or components within military medicine. For this purpose, the extent to which VBHC has been applied within a military health system (MHS), with emphasis on military trauma care was assessed. Design This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources Medline, Embase, Web of Science CC and the Cochrane CRCT databases were searched from 1946 to present for VBHC strategies and/or components and military settings, including associated keywords. Eligibility criteria for selecting studies We included observational and trial studies focused on the presence of VBHC components and/or system, and the presence of acute/trauma operational care or definitive postoperational care regarding combat injured service members. The included articles were classified into injury-related and system-level studies. Data extraction and synthesis Two independent reviewers used standardised methods to search, screen and code included studies. For quality assessment, the Mixed Methods Appraisal Tool version 2018 was used. Results A total of 3241 publications were screened, and 18 were included for data extraction. 15 studies focused on (military) medical trauma-related conditions (injury groups), and 3 studies focused on an MHS approach. Four articles contained the two VBHC components (‘creating an integrated practice unit’ and ‘measuring outcomes and costs for every patient’) considered the basis for successful implementation. The ‘outcomes and costs’ and ‘patient-centred care’ components were most prevalent as respectively mentioned in 17 and 8 included studies. Conclusion The systematic review showed the application of VBHC components in military medicine, although use of standard VBHC terminology is not consistently applied. This study suggests that implementing VBHC as a concept in military healthcare, could enhance benchmarking to provide insight in health outcomes (both clinically and patient-reported), and overall quality of care.

Introduction The burden of non-communicable diseases (NCDs) has increased substantially in low- and middle-income countries (LMICs), and adapting health service delivery models to address this remains a challenge. Many patients with NCD seek private care at different points in their encounters with the health system, but the determinants and outcomes of these choices are insufficiently understood. The proposed systematic review will help inform the governance of mixed health systems towards achieving the goal of universal health coverage. This protocol details our intended methodological and analytical approaches, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Methods and analysis Following the PRISMA approach, this systematic review will develop a descriptive synthesis of the determinants and outcomes of private healthcare utilisation for NCDs in LMICs. The databases Embase, Medline, Web of Science Core Collection, EconLit, Global Index Medicus and Google Scholar will be searched for relevant studies published in English between period 1 January 2010 and 30 June 2022 with additional searching of reference lists. The study selection process will involve a title-abstract and full-text review, guided by clearly defined inclusion and exclusion criteria. A quality and risk of bias assessment will be done for each study using the Mixed Methods Appraisal Tool. Ethics and dissemination Ethical approval is not required because this review is based on data collected from publicly available materials. The results will be published in a peer-reviewed journal and presented at related scientific events. PROSPERO registration number CRD42022340059

Age-related diseases, like Alzheimer’s disease and type 2 diabetes mellitus, are characterized by protein misfolding and the subsequent pathological deposition of fibrillized protein, also called amyloid. Several classes of amyloid-inhibitors have recently been tested, traditionally under bulk conditions. However, it has become apparent that amyloid fibrils and oligomers assemble and exert their cytotoxic effect at cellular membranes, rather than in bulk solution. Knowledge is therefore required of inhibitor activity specifically at the phospholipid membrane interface. Here we show, using surface-specific sum-frequency generation (SFG) spectroscopy and atomic force microscopy (AFM), that the commonly used (−)-epigallocatechin gallate (EGCG) is a much less efficient amyloid inhibitor at a phospholipid interface than in bulk solution. Moreover, EGCG is not able to disaggregate existing amyloid fibrils at a phospholipid interface, in contrast to its behavior in bulk. Our results show that interfaces significantly affect the efficiency of inhibition by EGCG inhibitors and should therefore be considered during the design and testing of amyloid inhibitors.

The formation of amyloid fibrils is a self-assembly process of peptides or proteins. The superior mechanical properties of these fibrils make them interesting for materials science but constitute a problem in amyloid-related diseases. Amyloid structures tend to be polymorphic, and their structure depends on growth conditions. To understand and control the assembly process, insights into the relation between the mechanical properties and molecular structure are essential. We prepared long, straight as well as short, worm-like β-lactoglobulin amyloid fibrils and determined their morphology and persistence length by atomic force microscopy (AFM) and the molecular conformation using vibrational sum-frequency generation (VSFG) spectroscopy. We show that long fibrils with near-100% β-sheet content have a 40-times higher persistence length than short, worm-like fibrils with β-sheet contents below 80%.