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Systematic Reviews

Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match Systematic Reviews's content profile, based on 11 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Promise vs. Proof in Digital Interventions for Antimicrobial Stewardship: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Matos Porto, A. P.; Gomes, M. S.; de Oliveira, V. F.; Mwanja, H.; Zhu, N.; Holmes, A.; Levin, A. S.; Costa, S. F.

2026-06-03 infectious diseases 10.64898/2026.06.01.26354656 medRxiv
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Background: Digital antimicrobial stewardship (AMS) interventions, such as clinical decision support systems, audit and feedback platforms, and electronic prescribing tools, have been increasingly adopted to improve antibiotic use. However, the effectiveness of these interventions across healthcare settings remains uncertain, and the certainty of the evidence has not been comprehensively evaluated. The objective of this study was to provide a comprehensive understanding of the role of digital interventions in optimizing antimicrobial use and improving clinical outcomes within a broad spectrum of healthcare settings. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials evaluating digital AMS interventions that followed PRISMA 2020 guidelines and registered in PROSPERO CRD420251178854 and funded by the Wellcome Trust CAMO Net programme. Searches were performed across major databases. Primary outcomes included the appropriateness of antibiotic prescriptions and the antibiotic prescription rate. Secondary outcomes included 30 day mortality, 30 day hospital readmission, and length of hospital stay (LOS). Random effects models were used to pool effect sizes. Risk of bias was assessed RoB 2, and certainty of evidence was rated using GRADE. A Summary of Findings table was prepared to present effect estimates, sample sizes, and evidence certainty. Results: Eleven RCTs met the inclusion criteria, and nine were included in the quantitative synthesis. Digital AMS interventions did not show a significant effect on appropriateness of antibiotic prescribing (RR 0.99, 95%CI 0.93 to 1.05; very low certainty). There was no reduction in antibiotic prescription (RR 0.98, 95%CI 0.88 to 1.09), with substantial statistical heterogeneity and very low certainty. Across clinical outcomes, digital AMS showed no effect on 30 day mortality (RR 0.91, 95%CI 0.77 to 1.09; very low certainty) or 30 day readmission (RR 0.95, 95%CI 0.79 to 1.14; very low certainty). For LOS, results were inconsistent across studies, and the pooled effect showed no clinically meaningful change (MD 0.17 days, 95%CI 0.01 to 0.35; very low certainty). Most trials had some concerns of bias due to deviations from intended interventions. Conclusion: Meta-analyses of digital AMS RCTs showed a lack of evidence with a high level of certainty on antibiotic prescribing or clinical outcomes due to high heterogeneity in interventions and study designs, as well as RCTs' limitations (no adoption/fidelity metrics).

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REduction of the lifting Load Among logistics workers through a passive back eXoskeleton. Protocol of the RELAX project, an 18-month in-field controlled intervention study

Jakobsen, L. S.; Skals, S.; Christiansen, D.; Sorensen, J.; Pontonnier, C.; MADELEINE, P.

2026-05-22 occupational and environmental health 10.64898/2026.05.21.26353770 medRxiv
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Background Occupational exoskeletons are used to reduce physical workload and prevent work-related musculoskeletal disorders in physically demanding jobs. Although laboratory studies demonstrate reduced muscle load during simulated manual work tasks, evidence from long-term, real-world implementations remains very limited. The RELAX project aims to investigate the long-term effects of a passive back-support exoskeleton (BSE) during manual order-picking work in a Danish warehouse, focusing on health and socio-economic outcomes. Methods This 18-month controlled in-field intervention study compares outcomes at two warehouse departments: one where workers use a passive BSE and a control group where workers perform work tasks as usual. Approximately 90 full-time workers will be followed during the intervention period with questionnaires, interviews and company-registered performance indicators. Primary outcomes include perceived work intensity and musculoskeletal discomfort, while secondary outcomes include sickness absence, employee turnover, productivity and cost effectiveness. Furthermore, a process evaluation will be conducted based on questionnaires, focus-group interviews, and reported exoskeleton use. Quantitative effects will be analysed using difference-in-difference analysis with generalized linear mixed models to account for repeated measures over time. Employee turnover will be analysed using time-to-event analysis, and qualitative focus-group interviews will be analysed using reflexive thematic analysis to explore implementation processes and contextual factors. Cost-effectiveness and return on investment will be assessed by comparing the investment with potential savings in costs and resource use. Discussion By combining longitudinal quantitative outcomes with qualitative process evaluation, the study seeks to provide ecologically valid evidence on the effectiveness, feasibility and sustainability of occupational exoskeleton implementation. This approach will help clarify whether long-term exoskeleton use improves worker health without compromising productivity and may inform future workplace guidelines and large-scale adoption strategies.

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Climate change and environmental pollutants - an international survey of naturopathic perceptions and clinical behaviour

Foley, H.; Lloyd, I.; Fitzpatrick, M.; Steel, A.

2026-06-02 occupational and environmental health 10.64898/2026.05.31.26354564 medRxiv
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Background: With rising concerns about health impacts from climate change and environmental exposures, planetary health approaches are increasingly prominent, considering connections between human health and that of the natural environment. Naturopathy is an holistic traditional medicine system characterised by philosophies and practices rooted in nature that theoretically align with planetary health. However, it is unknown to what extent these philosophies translate into consideration of relevant factors during patient care. This study describes the perceptions and clinical behaviours of the global naturopathic workforce in addressing the health impacts of climate change and environmental pollutants. Methods: A cross-sectional online survey was administered to an international sample of naturopathic practitioners, recruited through communications from World Naturopathic Federation member organisations. The survey utilised the Climate Change Perceptions Scale, and asked participants about their perceptions of the health impacts of climate change and environmental pollutants. The survey also examined participant considerations of factors relating to climate change and environmental pollutants during clinical case assessment and prescribing of treatments. Data were descriptively analysed. Results: Of n=363 naturopathic practitioners who completed the survey, 88.7% agreed climate change is real, of whom the majority were concerned about impacts of climate change on their patients' health (89.1%). Almost all participants agreed that environmental pollutants harm human health (99.7%) and were concerned about impacts on their patients (99.5%). Climate-related health factors such as water intake (74.2%) and food security (72.9%) were frequently considered during patient assessment, while impacts of severe weather events (41.4%) were less commonly considered. Consideration of factors relating to environmental pollutants was more commonly reported, particularly for food quality (83.8%) and domestic/indoor sources of pollutants (73%). When formulating prescriptions, participants reported highly frequent consideration of all climate-related factors (73%-86.8%) and varied consideration of environmental pollutant exposures (54.4%-83.4%). Conclusions: The global naturopathic workforce demonstrates a high level of awareness and engagement with factors relating to health impacts of climate change and environmental pollutants, suggesting alignment with planetary health. While this engagement is evident in clinical behaviour, some gaps between awareness and application suggest a need for greater support to strengthen the naturopathic application of planetary and environmental health.

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Longitudinal Transdisciplinary Neuropalliative care Support (LOTUS) Study - a conceptual framework and fidelity assessments

Creutzfeldt, C. J.; Leonhardt-Caprio, A.; Nielsen, E.; Lee, R. Y.; Wahlster, S.; Holloway, R. G.; Reinke, L. F.

2026-06-02 neurology 10.64898/2026.05.29.26354486 medRxiv
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Importance: Severe stroke is a leading cause of death and disability worldwide. Survivors and their families face long-term unmet needs, including care that does not reflect patients' values, fragmented care, and high rates of psychological distress among caregivers. Objective: To describe the conceptual framework of the longitudinal transdisciplinary neuropalliative care support (LOTUS) intervention and assess its fidelity in a pilot feasibility study. Design: Pilot feasibility randomized study; fidelity was assessed using weekly checklists completed by the LOTUS nurse and qualitative analysis of weekly LOTUS team meeting transcripts. Setting: Single comprehensive stroke center in Western New York. Participants: Patients hospitalized with severe stroke and their caregivers. Dyads were randomized to usual care or intervention. Intervention: The LOTUS intervention is implemented in a stepped-care fashion using 5 strategies: Awareness, Assistance, Adjustment, Acceptance and Alignment (5As). Led by a specially trained nurse with a chaplain, social worker, psychologist, and neuropalliative care physician, the LOTUS team follows dyads from early in the hospital course through 6 months. Main Outcomes and Measures: Fidelity, the degree to which the intervention was delivered as intended, assessed via (1) utilization of 5A activities from weekly LOTUS checklists; (2) thematic analysis of weekly LOTUS team meeting transcripts. Results: Of 26 patients in the trial, 13 were randomized to intervention. The LOTUS nurse completed 108 checklists, with an average of 619 minutes of direct contact per participant over 6 months. Each component of the 5A's was utilized. Awareness and Assistance predominated early after enrollment and revolved around personhood, support, and self-efficacy. Adjustment was especially relevant during care transitions and was typically supported by the LOTUS social worker. Acceptance and Alignment were more prevalent during later meetings, with the LOTUS psychologist supporting identification and modeling of coping skills and the LOTUS physician guiding prognosis and goals-of-care conversations. The LOTUS nurse served as primary point of contact, providing continuity and a trusting relationship, while other team members functioned in a predominantly advisory role. Conclusions: The LOTUS intervention was delivered with fidelity to the 5A-framework, supporting a future randomized clinical trial to evaluate its efficacy in patients with severe stroke and their caregivers.

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The control gap in long COVID research: a meta-epidemiological analysis

Panagiotopoulos, A.-P.; Laskaris, A.; Tsakri, D.; Manoussopoulos, Y.; Anastassopoulou, C.; Tsakris, A.; Ioannidis, J.

2026-05-21 epidemiology 10.64898/2026.05.16.26353381 medRxiv
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Objectives To quantify the frequency of baseline control-group use in published long COVID prevalence studies and assess their key methodological features. Design Cross-sectional meta-epidemiological evaluation of published post-acute COVID-19 prevalence studies, supplemented by a corresponding-author survey. Setting Published studies identified through a systematic review by Hou et al. (2025) and supplementary data obtained through direct email contact with corresponding authors. Participants A total of 440 published long COVID prevalence studies. Main Outcome measures Presence and type of comparator group, reliance on solely self-reported outcomes, acknowledgment of lack of a control group among uncontrolled studies, and availability of additional comparator data through author survey. Results Among 440 studies, 372 (84.5%) reported no control group on their publication. Healthy or uninfected comparators were reported in 55 studies (12.5%) and other comparator types in 14 (3.2%); 1 study included both categories. Solely self-reported outcomes were used in 279 studies (63.4%). Among 372 uncontrolled studies, 244 (65.6%) did not explicitly acknowledge the absence of a baseline comparator as a limitation anywhere in text. Corresponding authors of 140 studies (31.8%) responded to the survey; among them, 126 (90.0%) reported no additional comparative data, while 14 (10.0%) mentioned some available comparative datasets (19 additional datasets). Almost all of that information (10/14, 17/19) had been already published in other articles not captured by the Hou et al. systematic review. Conclusions Most published long COVID prevalence studies lacked comparator groups and relied exclusively on self-reported outcomes without acknowledging this limitation. Direct author contact identified little additional comparator information. Much of the long COVID prevalence literature may therefore be poorly suited to estimating burden attributable specifically to SARS-CoV-2, underscoring the need for appropriately matched comparators and more objective outcome assessment. Registration The protocol was prospectively registered on the Open Science Framework (https://osf.io/f4hra).

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Development of an Open-Access Action Observation Video Library for Upper Limb Motor Rehabilitation

Madison, M.; Wheaton, L. A.; Rowe, V.

2026-06-10 rehabilitation medicine and physical therapy 10.64898/2026.06.10.26355108 medRxiv
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Background: Occupational therapists can improve stroke survivors hand and arm movement and participation in daily activities through action observation (AO). AO involves watching another persons hand or arm complete a movement or task. While research generally supports the use of AO with stroke survivors, there are limited AO videos are available to occupational therapists which makes applying AO challenging. Objective: The purpose of this work is to develop structured and widely accessible tool to support access to AO for stroke survivors, occupational therapists, and researchers. Methods: To develop an AO video library for stroke rehabilitation, functional and non-functional upper limb task deficits were first identified through clinical observations and clinician interviews to establish a prioritized list of daily activities. In collaboration with media production specialists, healthy adult volunteers were recruited and filmed performing these tasks from both first- and third-person perspectives. The recorded videos were then systematically edited, enhanced with instructional title slides, and distributed via a public YouTube channel for clinical application and a categorized digital repository for research purposes. Results: Initial assessments revealed a complete lack of familiarity, awareness, and utilization of AO resources among local occupational therapists, despite high perceived clinical utility. To address this gap, a final library of 150 tasks was established, resulting in the production of 419 finalized, standardized videos featuring six healthy volunteers. For clinical application, these videos were hosted on a free, public YouTube channel organized into 18 functional playlists, while a parallel set was structured into distinct movement categories for research repository storage. Conclusion: By providing a structured and highly accessible tool, this repository enables clinicians, researchers, and caregivers to readily implement evidence-based action observation interventions in both clinical and home settings.

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Generative Artificial Intelligence in Medical Education and Participatory Research for Social Action: A Human and AI Comparative Analysis

Juniu, S.; Castor, D.; Reyes Nieva, H.; Charon, R.; Amesty, S.

2026-05-21 medical education 10.64898/2026.05.14.26351842 medRxiv
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Participatory qualitative methods such as Photovoice are increasingly used to link research with social action. Recent advances in artificial intelligence (AI) may enhance data analysis, inference, and action planning within such participatory approaches. This study explored medical students' perceptions of social justice using conventional Photovoice analysis and assessed the potential contribution of generative AI (genAI). Nine students joined a six-week seminar, "Exploring the Concept of Social Justice Using Photovoice." An initial two-hour session covered ethics, the Photovoice framework, and photography techniques. Participants then captured images reflecting their views on social justice, wrote narratives, and engaged in guided group discussions. Human researchers and students conducted a three-stage Photovoice analysis: 1) selecting photographs, 2) contextualizing them with participant narratives, and 3) inductively coding themes. To explore how AI might support data analysis, the research team analyzed the same data with five generative tools including Sonix, ChatGPT, and Copilot. AI-generated themes and visual representations were compared with human-derived results for congruence, depth, and suggested action steps. Conventional analysis identified five major themes: (1) Social Justice and Inequality, (2) Contradictions and the Costs of Justice, (3) Community and Collective Action, (4) Environment and Environmental Justice, and (5) Perception, Subjectivity, and Perspective. AI-assisted analysis yielded six unified themes that closely aligned with human findings. Traditional Photovoice images conveyed authentic, lived experiences and strong emotional meaning, providing a powerful foundation for advocacy. AI-generated images and thematic summaries offered efficiency, creativity, and reduced researcher bias, improving generalizability. However, they lacked the emotional depth and contextual nuance present in participant-created visuals.

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Pandemic-related changes in postpartum depression and anxiety among breastfeeding mothers: a systematic review and meta-analysis

Yu, J.; McCann, M.; Clesham, M.; Fewtrell, M.

2026-05-20 epidemiology 10.64898/2026.05.18.26353483 medRxiv
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Background: The COVID-19 pandemic caused major disruptions to maternity care, breastfeeding support, and social networks. These changes may have increased the risk of postpartum depression, anxiety, and stress among breastfeeding mothers, a population that has been underrepresented in previous reviews. This systematic review and meta-analysis aimed to compare maternal mental health outcomes among breastfeeding mothers before and during the COVID-19 pandemic. Methods: We searched MEDLINE, EMBASE, AMED, Web of Science, WanFang Data, MedRxiv, WHO COVID-19 databases, and grey literature from database inception to December 2023. Eligible studies compared mental health outcomes in breastfeeding mothers before and during the COVID-19 pandemic using validated assessment tools, including the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder Scale (GAD-7), State-Trait Anxiety Inventory (STAI), or Perceived Stress Scale (PSS). Studies with fewer than 10 participants per group were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Joanna Briggs Institute checklist or Newcastle-Ottawa Scale, depending on study design. Random-effects meta-analysis was performed when at least two studies reported comparable outcomes. Results: Twenty-three studies involving breastfeeding mothers from 15 countries were included. Meta-analysis showed significantly higher depressive symptoms during the pandemic compared with the pre-pandemic period, measured by EPDS (standardized mean difference [SMD] = 0.21, 95% confidence interval [CI] 0.14 to 0.29). Maternal anxiety measured by GAD-7 was also significantly higher during the pandemic (SMD = 0.27, 95% CI 0.13 to 0.41). Findings for perceived stress were mixed across studies and could not be pooled because of heterogeneity in reporting methods. Limited evidence suggested that mother-infant bonding did not substantially decline during the pandemic despite increased maternal psychological distress. Conclusions: Breastfeeding mothers experienced increased postpartum depression and anxiety symptoms during the COVID-19 pandemic. These findings highlight the importance of maintaining breastfeeding support services, ensuring access to maternal mental health screening, and developing flexible models of postpartum care during future public health emergencies. PROSPERO registration: CRD42022354670.

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Acceptability and Perceptions of Artificial Intelligence in Organized Breast Cancer Screening: A Study of French Women

Jean, A.; Merceron, A.; Le Saux, A.; Mercier, E.; Benillouche, P.

2026-06-09 radiology and imaging 10.64898/2026.06.07.26354883 medRxiv
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This study aims to assess women's perceptions of artificial intelligence (AI) used in breast cancer screening in France by examining their knowledge of AI and the barriers to their participation in organized screening. The results of a survey conducted in June 2025 among a national sample of 2000 women (aged 40-75) reveal limited participation and persistent concerns among women. Nevertheless, despite a low awareness of specific AI applications, a large majority of the women surveyed are very favorable to the use of AI in breast cancer diagnosis, even considering it a lever to increase screening participation.

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Preclinical Safety Evaluation of Human Lactoferrin Alpha (Effera(R))

Peterson, R.; Baldwin, N.; Clark, A. J.; Kaminski, N. E.; Hoberman, A.; Pala, R.; Lewis, E.; Vaden-Harris, A.; Malinczak, C.-A.

2026-06-01 pharmacology and toxicology 10.64898/2026.05.28.728516 medRxiv
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The preclinical safety of human-equivalent lactoferrin alpha (heqLF; effera(R)), produced by Komagataella phaffii, was evaluated to support its use as a food ingredient in infant formula and products for young children. Genotoxicity was assessed using a bacterial reverse mutation (Ames) assay in five strains of Salmonella typhimurium and Escherichia coli, and an in vitro micronucleus assay in TK6 cells. Both studies followed OECD guidelines and were conducted up to the recommended limit concentrations (5000 {micro}g/plate and 2000 {micro}g/mL, respectively). A 14-day non-GLP juvenile dose range-finding study and a 13-week GLP juvenile rat toxicity study with a 4-week recovery phase were conducted under ICH S11 guidance. Neonatal Sprague-Dawley rats received heqLF at 0, 1500, 3000, or 5000 mg/kg body weight/day by twice-daily oral gavage from postnatal day 7 to 98. Bovine lactoferrin (bLF) and whey protein at 5000 mg/kg body weight/day served as reference controls. heqLF was non-mutagenic and non-clastogenic in both genotoxicity assays. In the 13-week juvenile rat study, no heqLF-related mortality, clinical signs, developmental, neurobehavioral, or immune toxicity effects were observed. Minor, non-adverse renal findings consistent with high protein intake were observed and largely reversed during recovery. Clinical pathology parameters fully resolved during recovery. Toxicokinetic evaluation showed no systemic accumulation. Based on the absence of toxicologically relevant adverse findings, heqLF is well tolerated at doses up to 5000 mg/kg body weight/day, establishing a no observed adverse effect level (NOAEL) of 5000 mg/kg/day, the highest dose tested, and supporting its safety across intended populations from birth to adulthood.

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Advancing brain health equity after traumatic brain injury: A multi-stakeholder global priority-setting study

Mollayeva, T.; SantAna, T. T.; Shaikh, U.; Spouge, R.; Hanafy, S.; Fuller-Thomson, E.; McDonald, M.; Colantonio, A.; Cee, D.; McGettrick, G.; Lawlor, B.

2026-05-27 neurology 10.64898/2026.05.19.26353566 medRxiv
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The impact of social parameters on brain health among people with traumatic brain injury (TBI) has been extensively documented. However, translation of this evidence into policy and clinical practice remains limited. This may reflect a lack of coordinated and equity-driven approaches to brain health that integrate diverse stakeholder perspectives, limiting progress toward equity-oriented research and service delivery models. We conducted a convergent parallel mixed-methods study guided by the REporting guideline for PRIority SEtting of health research (REPRISE). We utilized the PROGRESS-Plus framework (Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and context-specific parameters) to ensure systematic consideration of social parameters in the study. For Objective 1, we synthesized existing evidence on social parameters and brain health outcomes. For Objective 2, we surveyed people with lived experience of TBI, family members/friends, clinicians, researchers, and community leaders across the globe to assess their prioritization of social parameters relevant to brain health. For Objective 3, we integrated evidence synthesis and stakeholder input through a structured Round Robin consensus activity to prioritize actionable areas for feasibility and impact. The activity culminated in the development of a knowledge mobilization agenda designed to inform equity-centred policy, research, and clinical practice. In Objective 1, we identified 59 publications with evidence on the effect of PROGRESS-Plus parameters on brain health outcomes following TBI. Meta-research highlighted that education, age, and country-level indicators are prognostic for brain health after TBI. In Objective 2, the highest-ranked priorities of 113 stakeholders across four continents (North America, Europe, Africa, and Oceania) were education, access to benefits, and income. These priorities were at the centre of discussion in Objective 3, which comprised idea sharing, refinement and thematic clustering, and a final prioritization poll. The resulting final 15 priorities were organized into two tracks: Track A, actions feasible in the short term, and Track B, longer-term implementation priorities. Building on this priority-setting process, co-created with stakeholders around the globe, the findings provide a roadmap for integration of social parameters in TBI research, knowledge exchange, policy, and practice.

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Evaluating the effect of a health-promoting behavioural programme on student's quality of life, academic self-efficacy and health: Study protocol of the PROMESS-Group randomised controlled trial

Krikorian, A.; Lecocq, B.; Le Pen, M.; Rollet, A.; Gouy, E.; Mura, M.; Metais, A.; Spiegel, K.; Pelloux, S.; Haesebaert, J.; Rode, G.; Schlatter, S.

2026-06-02 public and global health 10.64898/2026.05.28.26354323 medRxiv
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Background: Medical and doctoral students in health sciences represent a strategic public health lever as future professionals who will have a lasting influence on healthcare practices and the overall quality of health systems. Impaired quality of life and mental health issues among these students, coupled with scarce prevention programmes, led us to develop PROMESS-Group, an innovative multimodal programme designed to promote healthier lifestyle habits among university students. Methods: We will conduct a 2-arm randomised, controlled, superiority monocentric trial to assess the effect of this programme on medical and doctoral students compared to a control group. The intervention will consist of six sessions covering stress, sleep and physical activity domains. Each session will include group and individual meetings led by trained peer experts, focusing on needs assessment, self-care education, and personalised goals setting. Students' quality of life, academic self-efficacy, and broader health outcomes will be assessed using validated questionnaires and objective tools at baseline, during, and post-intervention. Data will be analysed according to the intention-to-treat principle and presented in accordance with CONSORT guidelines. Ethical approval was obtained from the institutional review board (IRB2025021802). All procedures will be performed in adherence to the Helsinki Declaration. Discussion: This study will enable the generation of high-quality evidence to evaluate the programme's effects on students' quality of life and related psychosocial outcomes, and may inform evidence-based health promotion strategies in university settings. Trial registration: ClinicalTrials.gov: NCT07030751 (https://clinicaltrials.gov/study/NCT07030751?locStr=Lyon,%20France&country=FR&state=Auvergne-Rh%C3%B4ne-Alpes&city=Lyon&cond=promess%20group&rank=1), 06.12.2025 - retrospectively registered. This protocol study follows the SPIRIT guidelines (Appendix 1). Keywords: Doctoral student, health behaviour, medical student, quality of life, physical activity, sleep, stress

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Adaptable Stroke Education Improves Knowledge Across Diverse High School Settings

Namian, S.; DiBiase, R.; Elnazer, S. H.; Evers, C.; Fung, C.; Narula, R.; Rafferty, M.; Salahuddin, A.; Sardana, D. J.; Shea, J.; Sullivan, M.; Forman, R.

2026-05-18 neurology 10.64898/2026.05.14.26353185 medRxiv
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Background: High school students may be able to communicate health topics to peers and adults. Yet, few studies have evaluated the role of high school students in community health initiatives, making them an underutilized group for disseminating health information. We pilot tested stroke education across five high schools using varied delivery approaches as a preliminary step toward evaluating youth stroke education to improve community health. Methods: In April-May 2025, five high schools in Connecticut and New York participated in stroke education. The format was designed to fit the needs of each school and included an 8-session classroom curriculum (Derby, CT), after-school club meetings (New Haven, CT; Long Island, NY), and one large assembly (Bridgeport, CT). Developed by teachers and neurology providers, the curriculum covered stroke risk factors, symptoms, and emergency response. Students completed a 15-point assessment adapted from the validated Stroke Action Test before, immediately after, and 4-6 weeks post-intervention; data were collected between April and July 2025. Results: Of 112 students completing the pre-test, 99 (88%) completed the immediate post-test and 51 (46%) the delayed follow-up. Average scores rose from 47% pre-intervention to 75% post and 70% at 4-6 weeks. All schools scored <50% on pre-tests suggesting poor baseline stroke knowledge. Conclusion: This pilot suggests that stroke education can be delivered to high school students across varied settings and may support knowledge gains up to 6 weeks. Limitations included small sample sizes and missing follow-up data. If validated in larger studies, this adaptable, teacher-supported approach could offer a scalable public health strategy for improving community stroke preparedness.

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Polystyrene Nanoplastics Disrupt Mouse Placenta Development in a Sex-Dependent Manner

Alahmadi, H.; Harbolic, A.; De Oliveria-Cordova, C.; Reynolds, R.; Jojy, M.; Potts, C.; Doan, S.; Mathur, T.; Islam, M. S.; Andrade, M. J.; Smith, Q.; Stapleton, P.; Mitra, S.; Warner, G. R.

2026-05-26 pharmacology and toxicology 10.64898/2026.05.22.727211 medRxiv
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Plastic production has been increasing exponentially. Throughout their lifespan, plastics degrade into smaller particles that accumulate in our bodies and the environment. Recent studies found these plastic particles can cross the placental barrier and reach the fetus. However, the impact of plastic particles on placental function is still unknown. We hypothesized that nanoplastics would disrupt placental growth and function, specifically focusing on transforming growth factor beta (TGF{beta}) signaling. To understand the impact of plastic particles on the placenta, we orally exposed pregnant CD-1 mice to 50 nm or 200 nm polystyrene plastic particles from gestation day 8 to day 15 at a human-relevant concentration of 5 mg/kg/day. After euthanization on day 15, placenta and fetus weights were recorded, and tissues were prepared for histomorphology and gene expression analysis. We observed a statistically significant decrease in the area of the decidua in the placentas for the 200 nm treatment group and a borderline significant decrease in decidua area for the 50 nm treatment group compared to control. However, when we separated by sex, only the male decidua were significantly decreased in the 200 nm group. Gene expression analysis of key signaling factors in the TGF{beta} pathway identified increased expression of Smad2 and Smad3, which may be suppressing prolactin and estrogen receptor signaling. Overall, both particle sizes disrupted placenta structure and signaling in a sex-dependent manner and may be acting as endocrine disruptors.

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COVID-19 vaccination and the risk of cardiovascular and thromboembolic events after SARS-CoV-2 infection: a systematic review and meta-analysis

Heymans, S.; Heidecker, B.; Marjenberg, Z.; Green, R.; Pliakas, T.; Lip, G. Y. H.; Lüscher, T. F.; Abduljawad, S.

2026-05-22 infectious diseases 10.64898/2026.05.21.26353568 medRxiv
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Background and Aims SARS-CoV-2 infection is associated with an increased risk of cardiovascular, cerebrovascular and venous thromboembolism events. We aimed to assess the impact of COVID-19 vaccination prior to SARS-CoV-2 infection on the risk of these events post-infection. Methods Embase and MEDLINE were searched from January 2021 to 11 September 2025, supplemented by citation searching. Observational studies were included if they reported risks of cardiovascular, cerebrovascular, or venous thromboembolic events after SARS-CoV-2 infection between different vaccination groups (e.g. unvaccinated, vaccinated, or booster vaccinated), or reported risk of events after SARS-CoV-2 infection compared with no infection, stratified by vaccination status. Random-effects meta-analyses were conducted to estimate pooled hazard ratios (HRs) comparing vaccinated and unvaccinated individuals across prespecified outcomes. Results Twenty-three studies were included in the systematic review; most reported an association between vaccination and a reduced risk of post-infection vascular events. Ten studies were included across meta-analyses comparing vaccinated and unvaccinated individuals. Pre-infection vaccination was associated with significantly reduced risks of composite cardiovascular/cerebrovascular events (HR 0.60, 95% confidence intervals [CI] 0.51-0.69), stroke (HR 0.75, 95% CI 0.64-0.88), acute coronary syndrome (HR 0.70, 95% CI 0.52-0.95), arrhythmias (HR 0.82, 95% CI 0.69-0.98), and venous thromboembolism (HR 0.51, 95% CI 0.36-0.73). No statistically significant reduction was observed for heart failure (HR 0.72 [95% CI 0.47-1.10]). Conclusions Pre-infection COVID-19 vaccination is associated with lower risks of cardiovascular, cerebrovascular and venous thromboembolism events following SARS-CoV-2 infection in the pre- and post-Omicron eras, supporting its role within broader prevention strategies

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Cardiovascular disease burden, trends, and projections in Vietnam, 1990-2050: a first comprehensive national analysis from the Global Burden of Disease Study 2023

Truyen, T. T. T. T.; Bao Le, P. N.; Ton Luu, B. M.; Le, K. L.; Nguyen, T. M. L.; Nguyen, H. Q. T.; Pham, K. A. T.; Nguyen, H.-D. T.

2026-05-17 cardiovascular medicine 10.64898/2026.05.13.26353134 medRxiv
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Introduction Cardiovascular disease (CVD) remains Vietnam's leading cause of mortality, yet no comprehensive national analysis of burden trends and future projections exists. This study characterizes Vietnam's CVD burden from 1990 to 2023 and projects burden through 2050. Methods Using Global Burden of Disease 2023 data, we analyzed CVD prevalence, incidence, mortality, and disability-adjusted life years (DALYs) in Vietnam from 1990 to 2023, stratified by sex and age. Joinpoint regression quantified temporal trends. Decomposition analysis separated contributions of population growth, aging, and epidemiological change. ARIMA modeling, validated against pre-pandemic and COVID 19 periods, projected burden through 2050. Results Despite age-standardized CVD prevalence below global estimates, stroke mortality and DALYs rates exceeded global benchmarks. Age-standardized CVD mortality (ASMR) declined significantly (average annual percentage change [APC]:-1.34%), yet absolute deaths nearly doubled from 121,611 to 223,068. Population aging contributed 140.9% to observed mortality increases while epidemiological improvements averted over 102,000 deaths. Male age-standardized CVD mortality was approximately twice that of females. High systolic blood pressure remained the leading attributable risk factor, while high BMI and alcohol use showed the largest rank escalations. CVD incidence reversed its declining trend during 2019 - 2023 (APC:+0.69%). By 2050, ASMR are projected to decline by 51.0% (218.8 to 107.1 per 100,000 [95%CI: 64.1 - 150.2]), while absolute deaths are projected to increase by 43.4% (206,677 to 296,335 [95%CI: 272,323 - 320,348]). Conclusions Vietnam faces a demographic paradox of improving age-specific outcomes alongside a rising absolute burden driven by population aging, demanding urgent reorientation toward aging-specific prevention, hypertension control, and chronic cardiovascular care.

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Consumer-Product Chemical Mixture and Systemic Inflammation: Survey-Weighted Analysis of Seven Urinary Biomarkers in NHANES 2005-2010

Jobe, N. I.

2026-06-10 occupational and environmental health 10.64898/2026.06.08.26355076 medRxiv
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Background: Endocrine-disrupting chemicals (EDCs) in consumer products are ubiquitously detected in human biospecimens, yet most epidemiological studies examine single chemicals rather than real-world co-exposures. We evaluated associations between a mixture of seven urinary chemical biomarkers and systemic inflammation. Methods: Survey-weighted log-log regression models adjusted for age, sex, race/ethnicity, poverty-income ratio, and survey cycle were conducted with Benjamini-Hochberg FDR correction (primary analysis, N=4,864). A sensitivity analysis additionally adjusted for body mass index and smoking status (N=4,494). Results: In the primary analysis, 5 of 7 chemicals showed significant associations after FDR correction: ethylparaben ({beta} = -0.056, FDR P < .001), propylparaben ({beta} = -0.026, FDR P = .007), bisphenol A ({beta} = +0.052, FDR P = .005), monoethyl phthalate ({beta} = +0.043, FDR P = .002), and monocyclohexyl phthalate ({beta} = +0.215, FDR P = .007). The WQS mixture index was significantly associated with CRP ({beta} = +0.056, 95% CI [0.031, 0.081], P < .001), with monocyclohexyl phthalate carrying the largest mixture weight (0.342). In the BMI- and smoking-adjusted sensitivity analysis, associations attenuated to null for all chemicals, though MCP preserved direction ({beta} = +0.129) and the WQS mixture direction was maintained ({beta} = +0.018). Two multiple imputation sensitivity analyses confirmed that monocyclohexyl phthalate was the only chemical to maintain a positive direction across all four analytical specifications (primary complete-case, BMI-adjusted complete-case, primary-aligned imputation, and BMI-adjusted imputation), reaching statistical significance in three of four specifications and providing convergent evidence of a robust MCP-inflammation association. Conclusions: The chemical mixture showed a significant collective association with systemic inflammation, consistent with a cumulative pro-inflammatory burden from co-exposure to multiple consumer product chemicals. These findings suggest that regulatory approaches should shift from single-chemical to mixture-based risk assessment frameworks for consumer product safety.

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A Pilot Study of the EMPOWER Music-based Intervention to Reduce Pulmonary Air Trapping in COPD

Taylor, J.; Choi, J.; Abdolijomoor, A.; Brunkan, M. C.; Wilson, A. L.; Castro, M.; Stewart, N.; Hanson-Abromeit, D.; Lepping, R. J.

2026-06-02 respiratory medicine 10.64898/2026.05.26.26350616 medRxiv
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Rationale: Air trapping in functional areas of the lung is common in chronic obstructive pulmonary disease (COPD). We developed a novel music-based intervention, Engagement of Music for Pulmonary Obstruction With Expiratory Restoration (EMPOWER) aimed at reducing air trapping and functional small airways disease (fSAD) in patients with COPD. Objectives: We conducted a pilot study to assess if air trapping and fSAD in COPD patients are reduced by our targeted EMPOWER music-based singing intervention. Methods: Participants completed four weeks of singing and vocalizing with a board-certified music therapist. Pre- and post-intervention assessments of standard pulmonary function tests (PFTs), and quantitative computed tomography (qCT) lung imaging documented changes in air trapping. Pre- and post-intervention change in psychological and patient-reported outcomes of hope, emotional wellbeing, agency and COPD symptom burden were also obtained. Main Results: All five adult participants with COPD who enrolled completed the study and reported strong interest in continuing with a similar program. Additionally, we observed trends toward improvement in qCT-measured fSAD, six-minute walk distance, and patient-reported symptoms on the COPD Assessment Test. Conclusion: Results of this preliminary study showed improvements in both patient-reported and imaging-indicated respiratory outcomes, suggesting that targeted singing components in music-based interventions such as the EMPOWER intervention may support physiological lung function changes in COPD patients.

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Primary Care Providers Journey with OSA Care, Challenges and Strategies: A Qualitative Study

Cho, W.; Cheng, M.; Blades, K.; David, O.; Tsai, W.; Povitz, M.; McBrien, K.; Donald, M.; Pendharkar, S.

2026-05-20 respiratory medicine 10.64898/2026.05.15.26353339 medRxiv
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Purpose: Obstructive sleep apnea (OSA) is a treatable chronic condition associated with significant health and societal consequences. Primary care providers (PCPs) often manage OSA with support from sleep specialists but face challenges navigating a complex system of care. By developing a Journey Map, we sought to identify factors influencing primary care OSA management and the associated PCPs' perspectives and emotions. Methods: Twenty-one Calgary-based PCPs were interviewed as part of a study evaluating a primary care management pathway for OSA. We used conventional content analysis, utilizing inductive coding to define journey phases and deductive coding via the Theoretical Domains Framework (TDF) to identify barriers and enablers. These were then mapped onto journey phases for OSA management to create a Journey Map. Results: The Journey Map included five phases of OSA care. PCPs described feeling neutral during the Learning phase and expressed neutral to positive emotions during the Patient Encounter and Diagnosing OSA phases. In contrast, the Initial Treatment and Ongoing Management phases were associated with neutral to negative emotional experiences. Barriers included limited OSA-related training and education, unclear roles among provider groups, and low patient engagement. Enablers included accessible knowledge resources, a shared key role in OSA screening, and availability of sleep testing. Opportunities to enhance primary care OSA management were identified at each step. Conclusion: This study identified several behavioural factors influencing PCP decision-making across the OSA care continuum. The Journey Map illustrates how high diagnostic confidence of PCPs shifts to escalating challenges and negative sentiment during treatment and long-term management of OSA. Keywords: obstructive sleep apnea; primary health care; health service delivery; process assessments; attitude of health personnel

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Neighborhood Deprivation and Disparities in Blood Pressure Monitoring in Patients with Intracerebral Hemorrhage

Namian, S.; Smith, J.; Constantinescu, S.; Tawaldemedhen, Y.; Rivier, C. A.; Clocchiatti-Tuozzo, S.; Huo, S.; Wu, K.; Forman, R.; Torres Lopez, V.; Sunmonu, N. A.; Petersen, N. H.; Falcone, G. J.

2026-06-01 neurology 10.64898/2026.05.22.26353704 medRxiv
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Background: Patients in socioeconomically disadvantaged neighborhoods face barriers to care. Missing BP documentation may signal gaps in risk-factor management, a crucial component of primary and secondary prevention of intracerebral hemorrhage (ICH). We tested whether neighborhood deprivation was associated with absent electronic health record (EHR) blood pressure (BP) documentation surrounding ICH and whether absent documentation predicted subsequent uncontrolled BP. Methods: We conducted a case-only study within the NIH All of Us Research Program. We included ICH survivors (ICD-10 I61.x, surviving >=1 year) with available ZIP3-based Deprivation Index. Deprivation was categorized as Privileged, Intermediate, or Deprived using cohort-based tertiles. We excluded BP measurements collected by All of Us. Outcomes were (1) absent EHR-derived BP documentation and (2) uncontrolled BP (mean systolic BP >=140 mmHg) during three windows: 1-365 days before ICH; 30-365 days and 1-5 years after ICH. Multivariable logistic regression tested associations adjusting for age, sex, and race/ethnicity. Results: 1,474 ICH survivors were included (mean age 60.1, 50.4% female). Compared to privileged neighborhoods, those living in deprived neighborhoods had higher odds of absent EHR BP documentation in the year prior to ICH (OR 2.10, 95% CI 1.60-2.76; p<0.001), 30-365 days post-ICH (OR 2.82, 95% CI 2.14-3.73; p<0.001) and 1-5 years post-ICH (OR 2.81, 95% CI 2.13-3.71; p<0.001). Absence of EHR BP documentation in the year before ICH predicted uncontrolled BP 30-365 days (OR 1.97, 95% CI 1.36-2.85; p<0.001; N=888) and 1-5 years (OR 1.83, 95% CI 1.24-2.69; p=0.002; N=814) after ICH. Absence of BP documentation 30-365 days post-ICH also predicted uncontrolled BP 1-5 years post-ICH (OR 1.66, 95% CI 1.10-2.50; p=0.017; N=814). Conclusions: Neighborhood deprivation is associated with persistent gaps in EHR BP documentation surrounding ICH, and absent documentation before or soon after ICH predicts subsequent uncontrolled BP. These findings highlight the need for community-level strategies that ensure equitable BP monitoring for socioeconomically disadvantaged populations.