The impact of sex and gender on the multidisciplinary management of care for persons with Parkinson's disease

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The endothelial transcription factor ERG promotes vascular stability and growth through Wnt/β-catenin signaling.

Blood vessel stability is essential for embryonic development; in the adult, many diseases are associated with loss of vascular integrity. The ETS transcription factor ERG drives expression of VE-cadherin and controls junctional integrity. We show that constitutive endothelial deletion of ERG (Erg(cEC-KO)) in mice causes embryonic lethality with vascular defects. Inducible endothelial deletion of ERG (Erg(iEC-KO)) results in defective physiological and pathological angiogenesis in the postnatal retina and tumors, with decreased vascular stability. ERG controls the Wnt/β-catenin pathway by promoting β-catenin stability, through signals mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is decreased in ERG-deficient endothelial cells; activation of Wnt signaling with lithium chloride, which stabilizes β-catenin levels, corrects vascular defects in Erg(cEC-KO) embryos. Finally, overexpression of ERG in vivo reduces permeability and increases stability of VEGF-induced blood vessels. These data demonstrate that ERG is an essential regulator of angiogenesis and vascular stability through Wnt signaling.This work was funded by grants from the British Heart Foundation (PG/09/096 and RG/11/17/29256). A.V.S. is a recipient of a National Lung and Heart Institute Foundation Studentship. I.M.A. is a recipient of a DOC-fFORTE fellowship of the Austrian Academy of Sciences at the London Research Institute.This paper was published by Cell Press in Developmental Cell (GM Birdsey, AV Shah, N Dufton, LE Reynolds, LO Almagro, Y Yang, IM Aspalter, ST Khan, JC Mason, E Dejana, B Göttgens, K Hodivala-Dilke, Gerhardt, RH Adams, AM Randi, Developmental Cell 2015, 32, 82-96

Age and gender differences in non-motor symptoms in people with Parkinson’s disease

BackgroundNon-motor symptoms of Parkinson’s disease (PD) are highly prevalent and heterogenic. Previous studies aimed to gain more insight on this heterogeneity by investigating age and gender differences in non-motor symptom severity, but findings were inconsistent. Furthermore, besides examining the single effects of age and gender, the interaction between them in relation to non-motor functioning has -as far as we know- not been investigated before.ObjectivesTo investigate the association of age and gender identity -as well as the interaction between age and gender identity- with non-motor symptoms and their impact on quality of life.MethodsWe combined three large and independent studies. This approach resulted in a total number of unique participants of 1,509. We used linear regression models to assess the association of age and gender identity, and their interaction, with non-motor symptoms and their impact on quality of life.ResultsOlder people with PD generally had worse cognitive functioning, worse autonomic functioning and worse quality of life. Women with PD generally experienced more anxiety, worse autonomic functioning and worse quality of life compared to men with PD, whereas men with PD generally had worse cognitive functioning. In interaction analyses by age and gender identity, depressive symptoms and anxiety were disproportionally worse with increasing age in women compared to men.ConclusionOur findings indicate that both age and gender -as well as their interaction- are differentially associated with non-motor symptoms of PD. Both research and clinical practice should pay more attention to demographic subgroups differences and possible different treatment approaches with respect to age and gender. We showed how combining datasets is of added value in this kind of analyses and encourage others to use similar approaches

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC

The Application of Human-Centered Design Approaches in Health Research and Innovation: A Narrative Review of Current Practices

Göttgens I, Oertelt-Prigione S. The Application of Human-Centered Design Approaches in Health Research and Innovation: A Narrative Review of Current Practices. JMIR mHealth and uHealth. 2021;9(12): e28102.**Background** Human-centered design (HCD) approaches to health care strive to support the development of innovative, effective, and person-centered solutions for health care. Although their use is increasing, there is no integral overview describing the details of HCD methods in health innovations. **Objective** This review aims to explore the current practices of HCD approaches for the development of health innovations, with the aim of providing an overview of the applied methods for participatory and HCD processes and highlighting their shortcomings for further research. **Methods** A narrative review of health research was conducted based on systematic electronic searches in the PubMed, CINAHL, Embase, Cochrane Library, Web of Science, PsycINFO, and Sociological Abstracts (2000-2020) databases using keywords related to human-centered design, design thinking (DT), and user-centered design (UCD). Abstracts and full-text articles were screened by 2 reviewers independently based on predefined inclusion criteria. Data extraction focused on the methodology used throughout the research process, the choice of methods in different phases of the innovation cycle, and the level of engagement of end users. **Results** This review summarizes the application of HCD practices across various areas of health innovation. All approaches prioritized the user’s needs and the participatory and iterative nature of the design process. The design processes comprised several design cycles during which multiple qualitative and quantitative methods were used in combination with specific design methods. HCD- and DT-based research primarily targeted understanding the research context and defining the problem, whereas UCD-based work focused mainly on the direct generation of solutions. Although UCD approaches involved end users primarily as testers and informants, HCD and DT approaches involved end users most often as design partners. **Conclusions** We have provided an overview of the currently applied methodologies and HCD guidelines to assist health care professionals and design researchers in their methodological choices. HCD-based techniques are challenging to evaluate using traditional biomedical research methods. Previously proposed reporting guidelines are a step forward but would require a level of detail that is incompatible with the current publishing landscape. Hence, further development is needed in this area. Special focus should be placed on the congruence between the chosen methods, design strategy, and achievable outcomes. Furthermore, power dimensions, agency, and intersectionality need to be considered in co-design sessions with multiple stakeholders, especially when including vulnerable groups

Moving beyond gender identity: the need for contextualization in gender-sensitive medical research

Göttgens I, Oertelt-Prigione S. Moving beyond gender identity: the need for contextualization in gender-sensitive medical research. The Lancet Regional Health - Europe. 2023;24: 100548

An opportunity for patient-centered care: Results from a secondary analysis of sex- and gender-based data in mobile health trials for chronic medical conditions

Traditional medical practice has suffered from male bias, which can lead to sub-optimal treatment options for female patients and increase the incidence of severe side-effects in this population. Mobile health applications, mHealth apps, represent one essential component of the shift towards consumer-centered self-administered individualized health. To prevent sex-specific bias it is important that trials consider sex and gender when developing mHealth apps. We evaluated the inclusion and reporting of sex and gender at all levels in mHealth randomized controlled trials (RCTs). To this end, we conducted a secondary analysis of a large study database addressing the effectiveness of app interventions on clinical outcomes in patients with chronic medical conditions. We followed the 5 steps described in the framework by Arksey and O’Malley and the guidelines of the PRISMA-ScR. Of the 72 app-based RCTs which reported information about sex overall, 62 included individuals of both sexes. The concept of gender was not addressed in any of the studies. The consideration of sex aspects in the design, execution and reporting of mHealth RCTs was minimal or absent. To adequately address the health and preventative needs of the mHealth user population, sex and gender should be systematically included in the research, development and evaluation of mHealth applications

A genderful research world : rapid review, design, and pilot study of an interactive platform for curated sex and gender health research resources

Background: Integration of sex and gender into health research is best practice for designing and conducting equitable, rigorous scientific research. Many evidence-based resources exist to support researchers in this endeavour, but such resources often remain underutilized as they are difficult to find, are not publicly accessible, or are specific to a particular research phase, context, or population. The development and evaluation of a repository of resources was deemed important to create an accessible platform for promoting sex- and gender-integration in health research. Methods: A rapid review was conducted of critical resources for conducting sex and gender health research. These were integrated into a prototype website design (the Genderful Research World; GRW) that provided an interactive digital landscape for researchers to access these resources. A pilot study evaluated the GRW website for applicability, desirability, and usability with an international sample of 31 health researchers from various disciplines and career stages. Quantitative data from the pilot study was summarized with descriptive statistics. Qualitative data was summarized narratively and used to identify concrete elements for improvement in a second design iteration. Results: Results of the pilot study revealed that the GRW was considered user friendly and desirable by health researchers and helped them access relevant information. Feedback suggested that providing these resources in a playful way may enhance the experience of the user, particularly given the high ‘desirability’ scores and that users emphasized the interactive layout as being key to their intention to integrate it into their teaching endeavors. Key feedback from the pilot study (e.g., addition of resources specific to research with transgender populations, revision of website layout) was integrated into the current version of the website: www.genderfulresearchworld.com . Conclusions: The present research suggests a utility for a repository of resources for integrating sex and gender considerations into research, and that providing a logical, intuitive means of cataloguing and navigating such resources is critical for usability. The results of this study may inform the development of other novel researcher-directed resource curation efforts to address health equity issues and encourage and support health researchers to integrate a sex and gender perspective in their work.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedResearcherPostdoctoralGraduat

An opportunity for patient-centered care: Results from a secondary analysis of sex- and gender-based data in mobile health trials for chronic medical conditions

Wang J, Barth J, Göttgens I, Emchi K, Pach D, Oertelt-Prigione S. An opportunity for patient-centered care: Results from a secondary analysis of sex- and gender-based data in mobile health trials for chronic medical conditions. Maturitas. 2020;138:1-7.Traditional medical practice has suffered from male bias, which can lead to sub-optimal treatment options for female patients and increase the incidence of severe side-effects in this population. Mobile health applications, mHealth apps, represent one essential component of the shift towards consumer-centered self-administered individualized health. To prevent sex-specific bias it is important that trials consider sex and gender when developing mHealth apps. We evaluated the inclusion and reporting of sex and gender at all levels in mHealth randomized controlled trials (RCTs). To this end, we conducted a secondary analysis of a large study database addressing the effectiveness of app interventions on clinical outcomes in patients with chronic medical conditions. We followed the 5 steps described in the framework by Arksey and O’Malley and the guidelines of the PRISMA-ScR. Of the 72 app-based RCTs which reported information about sex overall, 62 included individuals of both sexes. The concept of gender was not addressed in any of the studies. The consideration of sex aspects in the design, execution and reporting of mHealth RCTs was minimal or absent. To adequately address the health and preventative needs of the mHealth user population, sex and gender should be systematically included in the research, development and evaluation of mHealth applications

Gender-aware Parkinson's care: a design-based study of patient perspectives on gender norms and gender-sensitive care

Göttgens I, Modderkolk L, Vermue P, Darweesh SKL, Bloem BR, Oertelt-Prigione S. Gender-aware Parkinson's care: a design-based study of patient perspectives on gender norms and gender-sensitive care. EClinicalMedicine . 2023;65: 102285.Background Gender dimensions are progressively recognised as a relevant social determinant of health in people with Parkinson's disease (PD). However, little is known about the impact of gender norms and stereotypes on illness experiences of men and women with PD and what they consider important focal points for gender-sensitive PD care.Methods We conducted two equity-centred design (ECD) sessions on December 7, 2022 and December 8, 2022, at the Radboud University Medical Centre in the Netherlands. This participatory multi-method approach includes patients in the research and design process and was used to explore the impact of gender norms and stereotypes in illness experiences and generate patient-driven recommendations for gender-aware Parkinson's care. Quantitative survey data and design-based data were descriptively analysed, and qualitative focus group discussions were thematically analysed.Findings This study included thirteen men and fifteen women with PD in the Netherlands. All participants were of Dutch descent, with a median age of 65.5 years and a median clinical disease duration of 4.2 years. The gendered stereotype that "people with PD are old men" affected both men's and women's perception of living with the disease and the perceptions of their social environment. Men described masculine stereotypes related to physical strength and provider roles, while women expressed those related to feminine physical appearance and caregiver roles, influencing their illness experiences. For some, these norms influenced personal behaviours, while for others, they affected experiences through societal attitudes.Interpretation Our findings suggested that several gender norms and stereotypes influence the illness experiences of men and women with PD, manifesting at ideological, interpersonal, and internalised levels. Some participants internalised these norms, affecting their coping behaviours, while others encountered them in broader ideological contexts that shaped societal attitudes and interpersonal relationships. To advance gender sensitive PD care, it's essential to explore the impact of gender roles and norms, especially regarding how they might impede coping strategies, care access and utilisation for individuals of diverse gender identities.Funding The Gatsby Foundation and co-funded by the PPP Allowance by Health similar to Holland. Travel reimbursements for participants were made available through a Parkinson's Foundation grant (PF-FBS-2026).Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 2023;65: Published October https://doi.org/10. 1016/j.eclinm.2023. 10228