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The management of diabetic foot ulcers in patients with peripheral artery disease remains challenging. Human placenta-derived cells (PDA-002), a mesenchymal stromal cell-like population obtained from full-term placental tissue, possess angiogenic and tissue regenerative properties. Participants were stratified based on peripheral artery disease status. A total of 159 individuals were randomly assigned to receive intramuscular PDA-002 at one of three doses (3 × 106, 10 × 106 and 30 × 106 cells) or a placebo. This Phase 2 multi-center, randomised, double-blind, placebo-controlled trial evaluated adults with chronic diabetic foot ulcers with and without peripheral artery disease. The primary efficacy endpoint was the proportion of participants achieving complete wound closure of the index ulcer within 3 months, with sustained closure maintained for an additional 4 weeks. PDA-002 was well-tolerated, with no treatment-related serious adverse events. Intramuscular PDA-002 treatment achieved the highest efficacy at the 3 × 106 cell dose within the peripheral artery disease subgroup (38.5% vs. 22.6% for placebo), meeting a stringent 4-week durability endpoint that surpassed the U.S. Food and Drug Administration's recommended 2-week sustainability criterion. PDA-002 shows promise as a breakthrough treatment for diabetic foot ulcers and peripheral artery disease, demonstrating efficacy with two intramuscular doses and no re-treatment.
Trial Registration: ClinicalTrials.gov identifier: NCT # 02264288
To analyse the impact of a participatory process of awareness and reflection on compassion, in the face of end-of-life processes, in students aged 12–23 years in six Spanish regions, and to understand how the participatory process can transform their compassion.
Mixed sequential transformative methodology with different phases. In the first phase, a prospective quasi-experimental design with evaluation pre-post in a single group will be adopted. The second phase is the intervention under study, which will consist of a Participatory Action Research with concurrent evaluations.
In the quantitative phase, 1390 students aged 12–23 from a Public University and a Public Secondary Education Institute across six different Spanish regions will be included. A single questionnaire will be administered before and after the Participatory Action Research to contribute to the process evaluation, incorporating four scales (compassion for others' lives, Death Anxiety Scale, basic empathy modified for adolescents and self-compassion). Responses will be recorded in the Research Electronic Data Capture system. For data analysis, comparison groups, change evolution and associations between variables will be examined, along with multivariate logistic regression models. In the qualitative phase of participatory action research, a promoter group will be established in each university and secondary school in every region. Qualitative data will be analysed following the authenticity, transferability, auditability and neutrality criteria. Discourse analysis triangulation will be conducted to achieve data saturation.
Implementing participative action research in the educational environment to improve students' compassion makes them capable of founding compassion communities to help those who have a terminal illness.
This study will adhere to the relevant EQUATOR guidelines, such as the Good Reporting of a Mixed Methods Study guideline, to efficiently report its results through the different steps of this mixed-methods study.
Participatory action research is a method that enables participants to act as researchers of the phenomenon under study, facilitating the immediate application of results within the context. Although students did not participate in the writing of the proposal grant or the research design.
This study registered on Clinical Trials (NCT06310434), was initiated in January 2024, and it will continue up to December 2026.
This multicentre study will contribute to the nursing community with an overview of compassion for those at the end of their lives among young people and provide the knowledge needed to cultivate compassion at universities and schools.
Implementing compassion programmes and death education in the educational environment will empower students to create a compassionate community. The double evaluation of the process will contribute to the qualitative databases.
Healthcare systems face a growing challenge: as technology advances, patients increasingly feel like data points in systems that prioritise efficiency over empathy. This paper addresses the global healthcare crisis of disconnection, arguing that fundamental change requires putting human experience at the centre through Caring Science principles in nursing.
COVID-19 clearly revealed this disconnect. While showcasing scientific advances, it exposed gaps in compassionate care and fair access globally. Nurses struggled to maintain human connection while dealing with resource shortages and isolation protocols, proving that advanced medical treatments alone cannot address the physical, emotional, spiritual, and social factors that influence health.
This work draws on peer-reviewed studies, contemporary research, and theories of human caring to demonstrate the global responsibility and urgent need for integrating caring practices into healthcare systems. Collectively, this evidence underscores both the necessity of intervention and the effectiveness of Caring Science as a strategy for transforming organisational practices while highlighting a pressing truth: healthcare systems worldwide must move beyond efficiency alone and intentionally weave caring practices into their structures.
This analysis examines Caring Science through three key areas: Relational, Organisational, and Global. Using Watson's Theory of Human Caring and current research, the paper shows how caring relationships can improve through thoughtful use of innovation. Recent healthcare improvements demonstrate promising results when technology integration enhances both nurse empowerment and patient outcomes within frameworks that prioritise human connection.
Future directions position Caring Science as a mature, evidence-informed framework for addressing healthcare's complex challenges. The paper calls for ‘sacred activism’—a commitment to protecting caring's essential dimensions while embracing beneficial innovation, positioning nursing to lead healthcare transformation through both the art and science of nursing that honours human dignity.
To examine the historical origins of ‘advanced’ nursing as a concept.
Historical analysis using primary source documentation.
Historical analysis of articles published in the American Journal of Nursing by the National League of Nursing Education from 1928 to 1950, supplemented by books and articles addressing nursing specialisation history. Articles were analysed chronologically to trace terminology development and strategic decision-making processes during this foundational period.
‘Advanced’ terminology was first introduced in 1933 by Isabel Stewart to distinguish university-based clinical specialisation from exploitative hospital ‘postgraduate courses’. The term served as a strategic tool for legitimacy and professional differentiation. World War II accelerated development through federal funding and increased specialisation demands. Louise McManus provided the first conceptual framework in 1949, defining ‘advanced’ education as ‘planned forward movement’ requiring new learning experiences beyond basic preparation. Master's degree requirements were established in 1952, creating educational structures that persist today.
The strategic introduction of ‘advanced’ terminology in the 1930s established foundational concepts that continue to influence contemporary advanced practice nursing development internationally.
Understanding these historical origins enables more informed policy development for countries implementing advanced nursing roles and helps resolve ongoing definitional confusion in international nursing practice.
This research addresses the gap in historical understanding of advanced practice nursing terminology origins. Main findings reveal the strategic nature of professional language in nursing's professionalisation. The research impacts international nursing education policy and contemporary advanced nursing role development across diverse healthcare systems.
This study adhered to guidelines for historical research methodology.
This study did not include patient or public involvement in its design, conduct, or reporting.
Social determinants of health (SDOH) factors are known to influence patient outcomes, but their effect on sepsis remains insufficiently studied. This research aims to investigate the relationship between SDOH factors and sepsis outcomes, highlighting opportunities to reduce health disparities and enhance patient care.
Retrospective study.
Level I trauma centre in Baton Rouge, Louisiana, USA.
Patients with sepsis aged 18–89 years. Patients discharged or transferred to hospice were excluded to prevent bias and misinterpretation of the findings.
Social Vulnerability Index (SVI), the Gini Index and the average distance to the nearest urgent care, emergency department and clinic.
In-hospital mortality, 30-day readmission and hospital length of stay (LOS).
2 tests, Mann-Whitney U tests and Cox regression.
Distance from urgent care is significantly associated with mortality (4.14 vs 3.24 miles, p
Mortality and LOS are closely linked to proximity to urgent care, while high SVI is notably associated with longer LOS. These findings highlight the significant impact of SDOH factors on sepsis outcomes and underscore the need for targeted interventions to address disparities in healthcare access and contextual health practices.
Opioid use disorder (OUD) is a chronic and severe psychiatric condition defined by a level of opioid use which significantly impairs interpersonal and social functioning. In the biopsychosocial model of addiction, research has shown that psychiatric, sociological and neurobiological factors individually affect OUD severity. However, how these factors interact in the determination of OUD severity remains poorly understood.
The Epigenetic Bonds of Opioid Use Profiles are a multidisciplinary project whose primary objective is to characterise psychiatric and social factors of OUD in a large cohort of patients. The secondary objectives are, first, to correlate psychosocial severity with blood-derived epigenetic biomarkers to provide a deeper understanding of determinants of OUD and, second, to examine over a 2 year follow-up the correlation between the evolution of OUD and psychosocial severity with epigenetic biomarkers at inclusion. An additional objective is to analyse the impact of drug consumption rooms on access to care for most severely affected patients with OUD. In total, 300 opioid users will be recruited at supervised injection sites in Strasbourg and Paris and at addiction care centres in Strasbourg and Lyon to explore four psychiatric (substance use disorders beyond opioids, depression, anxiety, post-traumatic stress disorder) and five social (social support and status, traumatic experiences, housing, imprisonment, access to care) factors. Opioid users will be followed for 24 months and reassessed for psychosocial factors at 3, 6, 12, 18 and 24 months. Opioid consumption will be measured in all subjects using questionnaires, complemented by toxicological screenings (mass spectrometry). Finally, DNA methylation and gene expression will be characterised in capillary blood using next-generation sequencing. Mixed models will be used to model the primary and secondary outcomes.
This ongoing study was approved by the French Ethics Committee ‘Sud Méditerranée III’ of University Hospital of Nîmes (approval 2023–2024, protocol IDRCB number 2022-A02477-36) and authorised by the French Data Protection Authority (authorisation decision DR-2023–277 in December 2023). Results will be presented in international and national conferences and published in peer-reviewed international journals.
by Tessy Luger, Felix Uhlemann, Florestan Wagenblast, Thomas Läubli, Barbara Munz, Manfred Schmolz, Monika A. Rieger, Benjamin Steinhilber
BackgroundWork-related musculoskeletal disorders (WMSDs) are prevalent in occupations characterised by high repetition and high force demands. Both factors not only evoke inflammatory and degenerative processes in affected musculoskeletal tissue, but also systemic responses identified by biomarkers in blood serum. Clarifying methodological aspects of biomarkers may provide insights into their predictive role in the pathway of developing WMSDs. This study will primarily assess reliability of systemic inflammatory biomarkers (CRP, TNF-α, IL-6, IL-1β) and immune cell reactivity by repeated measures in workers with constant workloads over time.
MethodsThis observational cross-sectional study will include two groups of workers: exposed group including workers exposed to higher upper-extremity physical workloads, especially affecting the elbow/forearm/hand-area; unexposed group, including office workers exposed to lower upper-extremity physical workloads. Recruited persons are screened against eligibility criteria followed by a medical anamnesis and blood analysis. Enrolled participants undergo nine repeated measurements once every two weeks, taking blood among others. Blood analyses will determine values of systemic inflammatory biomarkers and reactivity of immune cells. The absolute test-retest reliability of biomarkers and immune cell reactivity over time is assessed by the intra-class correlation coefficient applying two-way mixed-effects models. The relative test-retest reliability is assessed by the standard error of measurement.
DiscussionKnowledge of and models currently describing the pathological role of systemic inflammatory biomarkers are based on highly-controlled laboratory rat experiments. This study has the strength of assessing a human population under real-life conditions. The major challenge is in participant recruitment given the intensive and complex study design. The results of this study could provide fundamentals for initiating a cohort study and be used for developing work-related stress-recovery concepts for occupations with different physical demands to identify workers who may be at risk for developing WMSDs. German Clinical Trials Register (DRKS00031872, 25 May 2023).
by Francesco Colussi, Jacopo Favaro, Claudio Ancona, Edoardo Passarotto, Maria Federica Pelizza, Eleonora Lorenzon, Simone Ruzzante, Stefano Masiero, Giorgio Perilongo, Giovanni Sparacino, Irene Toldo, Stefano Sartori, Maria Rubega
Brain maturation from birth to adolescence involves profound transformations in neural dynamics, which can be studied in a minimally invasive manner using quantitative EEG. Most of the results published in the literature are based on spectral analysis approaches, which are extremely effective in detecting and assessing EEG rhythms. However, some aspects of EEG dynamics can only be investigated using nonlinear approaches, the use of which is still relatively unexplored in the pediatric population. The aim of the present paper is to assess the EEG differentiation of wakefulness from deep sleep (quiet sleep in neonates, stage N3 in older children) and its maturation across a wide developmental window (0–17 years) using the fractal dimension. Specifically, Higuchi fractal dimension (HFD) algorithm is used to analyse both wakefulness and sleep EEG recordings collected from 63 infants (aged 0-1 year) and 160 children (aged 2-17 years). To ensure methodological consistency, a data-driven criterion for the selection of HFD user parameters is implemented to enhance reproducibility. Our results show that HFD during wakefulness increases during the first year of life, followed by a stabilization or slight decrease in later years. In contrast, HFD during sleep exhibits a more stable profile, with only a mild increase over development. These findings are consistent with known neurodevelopmental processes—including synaptogenesis, pruning, and white matter maturation—and support the interpretation of HFD as a sensitive marker of large-scale integrative brain dynamics. These physiological trajectories of HFD both in wakefulness and sleep could be used as reference for future clinical applications in pediatric neurology and developmental monitoring.by Jakob Morén, Barbro Persson, Anna Sörman, Åke Lundkvist, Hanin Shihab, Marie Studahl, Malin Veje, Göran Günther, Gabriel Westman
BackgroundTick-borne encephalitis is a viral infection of the central nervous system that may cause severe illness and long-term sequelae, to which underlying mechanisms are not completely understood. Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) may be triggered by immunologic events, occur sporadically, and can cause autoimmune encephalitis. Following herpes simplex encephalitis and Japanese encephalitis, anti-NMDAR autoantibodies may develop and have been associated with relapse or impaired cognitive recovery. Tick-borne encephalitis has been shown to trigger anti-NMDAR encephalitis in sporadic cases, but the frequency of autoimmunization is unknown.
ObjectivesThe objective of this study was to assess the frequency of intrathecal anti-NMDAR antibody development following tick-borne encephalitis and to explore whether such antibodies could be relevant to cognitive complaints.
MethodsAdult patients with tick-borne encephalitis were included retrospectively from one cohort and prospectively from another. A stored post-acute cerebrospinal fluid sample was required for anti-NMDAR analysis. Two commercial kits (Euroimmun AG, Lübeck, Germany) were used to detect anti-NMDAR IgG antibodies in cerebrospinal fluid.
ResultsA total of 71 cerebrospinal fluid samples from 53 patients were analyzed for anti-NMDAR antibodies. Samples were obtained at a median of 91 days (range 21–471) after onset of central nervous system symptoms. Anti-NMDAR antibodies were detected in two samples from a single tick-borne encephalitis patient, corresponding to 1.9% of patients (95% CI: 0.05–10.1%).
ConclusionsThe development of intrathecal anti-NMDAR autoantibodies following tick-borne encephalitis is a rare event, and further studies are needed to clarify their potential relevance to cognitive outcomes in a minority of cases. Testing for anti-NMDAR antibodies in cerebrospinal fluid may be considered in patients who experience clinical deterioration following an initial recovery.
by Tom A. W. Schoufour, Linda Voogd, Kees L.M.C. Franken, Tom H.M. Ottenhoff, Ruud H.M. Wijdeven, Simone A. Joosten
Human leukocyte antigen E (HLA-E) communicates cellular health to natural killer (NK) cells through presentation of peptides derived from the leader sequence of classical major histocompatibility complex class I (MHC-I), inhibiting NK cell activation and lysis of healthy cells. Besides this canonical role, HLA-E can also present peptides from pathogens such as Mycobacterium tuberculosis (Mtb) to T cells and can inhibit phagocytosis by engaging with LILRB1/2. To identify additional HLA-E binding surface molecules, we utilized a CRISPR/Cas9 activation screen with HLA-E tetramers, which identified Stabilin (STAB)1 and STAB2 as novel interactors. This interaction depended on the nature of the peptide/HLA-E complex, whereby high affinity peptides did not permit the interaction while low affinity peptides did. Functionally, expression of STAB1 or STAB2 on THP-1 monocytes increased phagocytic uptake of HLA-E coated microbeads. These results provide the first evidence of an interaction between Stabilin receptors and specific HLA-E conformations.by Mostafa Bondok, Moses Kasadhakawo, John Onyango, Oscar Turya, Khumbo Kalua
PurposeTo determine the prevalence and causes of blindness and vision impairment (VI) among adults aged ≥50 years in Western Uganda.
MethodsA population-based cross-sectional survey was conducted in Western Uganda (July-August 2023) using RAAB7. Adults aged ≥50 years who had resided in the study districts for at least six months in the past year were eligible. Participants were identified through door-to-door household visits using a two-stage cluster sampling approach. Primary outcomes include prevalence of blindness and VI and its causes. Secondary outcomes include cataract surgical coverage (CSC), effective CSC (eCSC), refractive error coverage (REC), and effective REC (eREC).
ResultsA total of 3,125 participants were examined (54.1% female). The adjusted prevalence of blindness (presenting visual acuity (PVA) Conclusion
Blindness and vision impairment remain major public health issues in Western Uganda, primarily due to untreated cataract and uncorrected refractive error. Poor post-operative outcomes highlight the urgent need to improve surgical quality. These findings may guide targeted interventions and policy to strengthen eye care services.
To explore implementation patterns and perceived value of the SEXIT (SEXual health Identification Tool) method in the school health care (SHC) setting in Sweden.
Mixed method survey using an online questionnaire with closed and free-text response options.
115 SHC professionals who had completed SEXIT training responded to an online questionnaire (response rate 26%), between March and May 2024. Closed questions were answered on a five-point Likert scale, and responses trichotomised. Quantitative data were analysed using descriptive statistics, qualitative data with a deductive qualitative content analysis. CROSS guideline was used.
70 of 115 SHC professionals used SEXIT in their work. Findings suggest that SEXIT is appropriate and useful, supporting communication about topics such as sexual health and violence that both pupils and professionals may avoid addressing. Implementation patterns showed that 61% of those who had completed training also used SEXIT. 63% of those used SEXIT during regular health dialogues, but some did not use it with all pupils. The perceived value was that most SHC professionals felt that SEXIT helped them get a better understanding of the pupil's situation, an objection that it was too time-consuming.
Most SHC professionals who had completed SEXIT training used the method regularly and perceived the method as valuable and facilitating discussions about sexual ill health and experiences of violence with pupils. There are indications that SHC services fail to identify particularly at-risk young people. Sexual health inequity persists, as some structurally marginalised and vulnerable youths are excluded from the SEXIT dialogues. A follow-up study will focus on pupils' experiences.
This study validates SEXIT in a new setting, SHC, and is relevant for the promotion of sexual and reproductive health for all, and for preventing violence and sexual ill health among young people.
To combine, synthesise, and interpret qualitative evidence from studies exploring the causes, immediate responses, and preventive measures of needle stick injuries from the perspective of healthcare workers.
In this qualitative evidence synthesis, the qualitative data from the included studies were synthesised to identify overarching themes. The Preferred Reporting Items for Systematic Reviews and Meta-analysis flowchart, Joanna Briggs Institute tool, and Enhancing Transparency in Reporting the Synthesis of Qualitative Research checklist were used in the meta-synthesis process.
The MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, ProQuest, ClinicalKey and Scopus databases were searched between December 14 and December 31, 2024 for studies published between January 2000 and December 2024.
Nine primary research studies were included and the following themes were identified: unpredicted patient movement, casual attitude, recapping, excessive workload, scarcity of article or safety equipment, inadequate training or experience, vigilance, ongoing training, nurturing workplace culture, emotional response, re-living the injury and fear of reprimand.
Needle stick injuries result from a complex interplay of individual, administrative, engineering, and environmental factors, but there are potential solutions to address these issues.
Policymakers in healthcare settings would benefit greatly from an understanding of the causes, immediate responses, and preventive aspects of needle stick injuries. These findings can direct the creation of focused interventions and safety procedures by identifying important risk variables and useful coping mechanisms.
The causes, immediate responses, and preventive measures of needle stick injuries were explored. Findings can help develop protocols to lower needle stick injury rates and increase worker safety.
ENTREQ guidelines.
This research is a systematic review of published peer-reviewed studies.
PROSPERO registration number: CRD42024620673.
Targeted biologic therapies have transformed outcomes for individuals with psoriasis, a common immune-mediated inflammatory skin disease. The widespread use of these highly effective treatments has led to a growing number of individuals with clear or nearly clear skin remaining on continuous, long-term treatment. Personalised strategies to minimise drug exposure may sustain long-term disease control while reducing treatment burden, associated risks and healthcare costs. This study aims to evaluate the feasibility of a definitive pragmatic effectiveness trial of two personalised dose minimisation strategies compared with continuous treatment (standard care) in adults with well-controlled psoriasis receiving the exemplar biologic risankizumab.
This is a multicentre, assessor-blind, parallel group, open-label randomised controlled feasibility trial in the UK, evaluating two personalised biologic dose minimisation strategies for psoriasis. 90 adults with both physician-assessed and patient-assessed clear or nearly clear skin on risankizumab monotherapy for ≥12 months will be randomised in a 1:1:1 ratio to (1) patient-led ‘as-needed’ treatment, where risankizumab is administered at the first sign of self-assessed psoriasis recurrence, (2) therapeutic drug monitoring-guided treatment, with personalised dosing intervals determined using a pharmacokinetic model or (3) continuous treatment as per standard care, for 12 months. Participants will be invited to submit self-reported outcomes and self-taken photographs every 3 months using a bespoke remote monitoring system (mySkin app) and will attend an in-person assessment at 12 months. They may also request additional patient-initiated follow-up appointments during the trial if needed. The primary outcome is the practicality and acceptability of the two personalised biologic dose minimisation strategies, assessed as a composite measure including recruitment and retention rates, adherence to the assigned strategies and acceptability to both patients and clinicians. The feasibility of collecting healthcare cost and resource utilisation data will also be evaluated to inform a future cost-effectiveness analysis. A nested qualitative study, involving semistructured interviews with patients and clinicians, will explore perspectives on the personalised biologic dose minimisation strategies. These findings will inform the design of a future definitive trial.
This study received ethical approval from the Seasonal Research Ethics Committee (reference 24/LO/0089). Results will be disseminated through scientific conferences, peer-reviewed publications and patient/public engagement events. Lay summaries and infographics will be codeveloped with patient partners to ensure the findings are accessible for the wider public.
Smoking and vaping are especially prevalent among people with experience of psychosis (EoP), potentially increasing their toxicant exposure. Switching from tobacco smoking to vaping e-cigarettes reduces exposure to tobacco-related toxicants and likely associated diseases. We compared levels of nicotine and tobacco-related toxicant exposure among people with versus without EoP.
Cross-sectional study, secondary data analysis of Wave 5 (2018) of the Population Assessment of Tobacco and Health Study.
Data collection took place in the USA at the home of participants.
Data were from 5750 adults (aged >18 years) with and without EoP who smoked, vaped, did both or did neither. EoP was defined as ever being told by a health professional that you have schizophrenia, schizoaffective disorder, psychosis, a psychotic illness or psychotic episode.
Levels of urinary toxicants: nicotine metabolites, metals, volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs) among people with and without EoP. Analyses were adjusted for demographics, cannabis use and past 30-day smoking/vaping status, and were repeated after stratifying by smoking /vaping status.
Of the 5750 participants, 6.3% (n=361) reported EoP, and 93.7% reported no EoP. Levels of nicotine and TSNA metabolites, cadmium, uranium and some VOCs were significantly higher among participants with EoP compared with those without. However, when smoking, vaping and cannabis use were taken into account, the associations of EoP with nicotine and TSNA metabolites, and most of the VOCs, were attenuated and no longer significant.
Participants with EoP are exposed to more nicotine and tobacco-related toxicants than those without EoP, likely largely due to the high prevalence of smoking, vaping and cannabis use among this population.
FreshRSS 