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Ayer — Junio 16th 2026Tus fuentes RSS

Tuberculosis death prediction calculator for prospective use at diagnosis in resource-constrained programme settings: a statewide cohort study

Por: Shanmugasundaram · S. · Shewade · H. D. · Srinivasan · R. · Frederick · A. · Sabarinathan · R. · Harish · P. · Balu · D. · Melfha · J. M. · Gayathri · K. · Vijayaprabha · R. · Jeyakumar · A. · Kabir · D. · Eraivan · M. · Bhatnagar · T. · Murhekar · M. V.
Objectives

To develop predictive models for early and overall tuberculosis (TB) deaths for prospective use at TB diagnosis in resource-constrained TB programme settings.

Design

Statewide cohort study using routinely captured secondary data.

Setting

With the majority of TB deaths being early (within 2 months), India’s TB programme’s information management system (Ni-kshay)-dependent death prediction models (using age, gender, TB site, previous treatment, microbiological confirmation, HIV, diabetes and bank account availability) are not feasible for prospective use, as few variables are captured at diagnosis. Utilising routinely captured triage variables for severe illness at diagnosis (body mass index, pedal oedema, respiratory rate, oxygen saturation and ability to stand without support) from an ongoing statewide and state-specific differentiated TB care initiative to reduce TB deaths in Tamil Nadu state (southern India, 80 million population with 0.1 million annual notifications), robust models for prospective use were developed.

Participants

Adults (aged ≥15 years) with TB (not known to be drug-resistant at diagnosis) that were notified from public facilities of Tamil Nadu from July 2022 to June 2023.

Outcome measures

Early and overall (within 12 months of notification) TB deaths. Area under the receiver operating characteristic curve (AUC) was used to assess accuracy of models built using modified Poisson regression.

Results

Among 55 971 adults, the overall death rate was 7.4%, and 67.9% of the deaths were early. In predicting overall deaths, accuracy of the model using all Ni-kshay variables (AUC 0.716 (95% CI 0.707 to 0.725)) was as good as the model using triage variables for severe illness only (AUC 0.701 (95% CI 0.691 to 0.711)). To the latter, adding potentially capturable Ni-kshay variables at diagnosis (age, gender, TB site, previous treatment and microbiological confirmation) significantly improved model accuracy (AUC 0.754 (95% CI 0.745 to 0.763)). Further addition of remaining Ni-kshay variables did not improve accuracy significantly. Death prediction equations were generated for these models.

Conclusion

Simple and easily measurable triage variables for severe illness should be routinely captured at TB diagnosis. A death prediction calculator (http://44.208.93.99/) based on these variables (specifically triage variables for severe illness combined with age, gender, TB site, previous treatment and microbiological confirmation) may be used by Indian states and high TB burden countries seeking scalable, data-driven interventions to reduce TB deaths.

Ventilation strategies and outcomes after out-of-hospital cardiac arrest: protocol for a pre-planned sub-analysis of the STEPCARE trial

Por: Battaglini · D. · Gualdi · F. · Cammarota · G. · McGuigan · P. J. · Thomas · M. · Skrifvars · M. B. · Niemelä · V. H. · Reinikainen · M. · Bass · F. · Young · P. J. · Lilja · G. · Dankiewicz · J. · Hammond · N. E. · Hästbacka · J. · Levin · H. · Moseby-Knappe · M. · Saxena · M. · Tia
Introduction

After resuscitation from out of hospital cardiac arrest (OHCA), mechanical ventilation (MV) and respiratory management are fundamental to support patients in the intensive care unit (ICU) and to minimise secondary brain injury. Best practices for MV and association with clinical outcomes in patients with OHCA remain unclear.

Methods and analysis

This protocol describes a pre-planned respiratory-focused series of sub-analyses within the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, an ongoing interventional study evaluating 6-month mortality after randomisation in patients admitted to ICUs following OHCA. The primary aim is to describe real-world ventilator settings and gas-exchange targets during the first 72 hours after ICU admission in patients receiving invasive mechanical ventilation after OHCA. Secondary aims include to estimate the incidence of respiratory complications during ICU stay (eg, ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma); and to explore the association between early ventilator settings/gas-exchange parameters and 6-month outcomes (mortality and neurological status). Exploratory aim is to characterise weaning and extubation practices, including timing and failure rates.

Eligible patients will include adult STEPCARE participants receiving invasive MV after return of spontaneous circulation with available respiratory data recorded within the STEPCARE database.

Data collected in the STEPCARE trial that will be analysed include patients’ prehospital characteristics; clinical examination at hospital admission and at ICU admission; ventilator settings and arterial blood gases recorded at predefined time points during ICU stay. In particular: MV setting (mode, tidal volume, positive end-expiratory pressure, fraction of inspired oxygen, tidal volume, mechanical power, plateau/driving pressures), gas-exchange values (arterial partial pressure of oxygen and carbon dioxide, pH, arterial saturation of oxygen), timing of measurements and the occurrence/timing of respiratory complications and weaning outcomes.

Ethics and dissemination

The STEPCARE study has been approved by the regional ethics committee at Lund University (Dnr 2022-02425-01, Approved IRB on 2022-06-18) and by all ethics boards in the participating countries. No additional ethical approval is required for this predefined secondary analysis, as no further data collection or interventions will be performed. Findings will be disseminated through publication in peer-reviewed journals and, where appropriate, conference abstracts and presentations. Patients and the public were not involved.

ClinicalTrials.gov

NCT05564754.

Use of case-based, problem-based and team-based learning in public health education - a scoping review

Por: Mansoor · J. · Abdul Hameed · A. · Zaidi · T. W. · Naeem · F. U. A. · Mansoor · F. · Bilal · M. · Kadir · M. M.
Objectives

Active learning strategies, including case-based learning (CBL), problem-based learning (PBL) and team-based learning (TBL), have been extensively studied in clinical and basic science education; however, their application in public health programmes remains under-explored. Public health professionals address population-level challenges that differ substantially from clinical practice, making it necessary to evaluate whether these pedagogies are effective in this field. This review examines how CBL, PBL and TBL have been used in public health education and what outcomes have been reported.

Design

Scoping review was conducted using the Levac and Colquhoun framework, an adaptation of Arksey and O’Malley’s approach.

Data sources, eligibility and extraction

PubMed, Scopus and Google Scholar were searched for studies published between 2000 and 2025. Eligible studies included those involving students enrolled in undergraduate or postgraduate public health programmes, such as bachelor’s or master’s programmes in public health, epidemiology and biostatistics, global health, community medicine or health policy as well as employees working in public health-related fields. Data were extracted using a predefined template capturing study characteristics, population characteristics, student satisfaction and study objectives. All articles were thematically analysed.

Results

Overall, 22 studies were included. Of these, 11 focused on PBL, 2 on CBL, 3 on both CBL and PBL and 6 on TBL. Public health topics addressed included general public health practice (n=5), global health (n=3), health literacy or education (n=3) and occupational health or medicine (n=2); remaining studies covered leadership, nutrition, health behaviour, climate and health, ageing and mental health. Six themes emerged: skill development, real-world relevance, diversity and inclusion, blended learning, innovative approaches and challenges. Key challenges for PBL included cognitive overload and implementation constraints; for CBL, inequitable participation and resource-intensive implementation; and for TBL, increased student time burden and difficulty adapting to complex simulations.

Conclusion

Active learning methods enhance critical thinking and problem-solving in public health education but face implementation barriers, including faculty training requirements and resource constraints. Future research should examine long-term outcomes and the integration of emerging technologies.

Novel use of arm ergometry cardiopulmonary exercise testing for non-elective patients with chronic limb-threatening ischaemia: a feasibility trial

Por: Hodge · S. · Haque · A. · Quraishi-Akhtar · T. · Bryan · A. · Rogers · S. · Bowling · F. L. · Ghosh · J.
Objectives

To evaluate the feasibility, safety and acceptability of arm crank ergometry cardiopulmonary exercise testing (CPETarm) in patients with chronic limb threatening ischaemia (CLTI).

Design

Prospective feasibility single-arm cohort study.

Setting

A tertiary vascular surgery referral centre in Greater Manchester, UK.

Participants

Adult inpatients admitted with CLTI and scheduled for non-elective vascular intervention.

Interventions

Participants underwent bedside CPETarm using an incremental ramp protocol. Cardiopulmonary parameters measured included peak oxygen uptake, anaerobic threshold (AT), ventilatory equivalent for carbon dioxide at AT, peak work rate, oxygen pulse, maximum heart rate and respiratory exchange ratio.

Primary and secondary outcome measures

Primary outcomes were feasibility domains including eligibility, recruitment, test completion, safety, practicality, implementation and patient acceptability. Secondary outcomes included the ability to obtain clinically relevant CPET variables for perioperative risk stratification.

Results

60 patients underwent CPETarm. 74% of CLTI inpatients met eligibility criteria and 71% of eligible patients consented to testing. CPETarm was completed to volitional exhaustion by 95% of participants, with anaerobic threshold identified in 68%. No major adverse events occurred during testing or within 24 hours post-test. 90% of CPETarm assessments were completed within 48 hours of the decision to proceed with intervention, without delaying surgery. The procedure was well tolerated and acceptable to patients.

Conclusions

CPETarm is a feasible, safe and acceptable method for preoperative assessment in patients with CLTI who are unsuitable for conventional lower-limb CPET. Further research is required to establish modality-specific thresholds, evaluate prognostic value for postoperative outcomes and evaluate integration into perioperative care pathways.

Trial registration number

NCT06404229.

Association between the use of anti-herpetic drugs and subsequent initiation of Alzheimers disease drug treatment: Dutch population-based inception cohort study

Por: Alghamdi · A. · Balafas · S. · Bos · J. H. J. · van Munster · B. C. · Rafie · K. · Dolga · A. M. · Hak · E.
Objectives

To examine whether exposure to anti-herpetic drugs (AHDs: acyclovir, valacyclovir, famciclovir) is associated with reduced risk of Alzheimer’s disease (AD) treatment initiation.

Design

Population-based retrospective matched cohort study.

Setting

University Groningen community pharmacy database IADB.nl, covering approximately 125 Dutch pharmacies (1994–2024).

Participants

262 757 adults aged 50–80 years without prior dementia or AD treatment. Exposed individuals with antiherpetic prescriptions (n=23 887) were matched 1:10 to unexposed controls (n=238 870) by age, sex and calendar time.

Intervention

AHDs: acyclovir, valacyclovir, famciclovir.

Main outcome measures

Initiation of AD drug treatment, defined as at least two prescriptions for rivastigmine, donepezil, galantamine or memantine within 1 year. Cox proportional hazards models estimated HRs with 95% CIs, adjusted for comorbidities and medications. Analyses were stratified by period (1994–2018 vs 2019–2024) and drug type.

Results

During follow-up, 2495 participants initiated AD treatment. The age of the participants was 65 (SD 9), and 59% were female. Any AHD exposure was associated with 90% reduced hazard of AD treatment (HR 0.09, 95% CI 0.07 to 0.13, p

Conclusions

AHD exposure was consistently associated with markedly lower risk of AD treatment initiation, with similar findings observed in recent years. These findings support the hypothesis that herpesvirus reactivation may contribute to AD pathogenesis and suggest antiviral therapy could have preventive implications. Confirmation through prospective studies and randomised trials is needed.

Revisiting the role of structural connectivity-based parcellation in thalamic nuclei segmentation: Benchmarking against recent state-of-the-art methods

by Daniel H. Nguyen, Debottama Das, Ali Bilgin, Dianne Patterson, Matthew Hook, Chris Butson, Alberto Cacciola, Vinod Kumar Jangir, Manojkumar Saranathan

Leveraging diffusion tractography, connectivity-based parcellation (CBP) is one of the oldest methods for thalamic nuclei segmentation. The goal of this work was to reassess CBP using higher spatial resolution diffusion MRI data and reconstruction algorithms, and to compare it with recent state-of-the-art methods for thalamic nuclei segmentation. Furthermore, these methods were systematically evaluated against three histological atlases and one functional MRI–based atlas to examine their relative anatomical similarities and differences. High resolution diffusion and T1-weighted MRI data from 67 healthy individuals in the Human Connectome Project Young Adult database were analyzed. CBP was performed using probabilistic tractography with cortical targets derived from combining labels of the Human Connectome Project Multi-Modal Parcellation 1.0 atlas into 8, 11, and 23 regions. Results were compared against three recent methods: orientation distribution function clustering (ODF), track density imaging (TDI), and structural MRI-based segmentation. Group level analyses were conducted in the Montreal Neurological Institute space, and Dice overlap coefficients were calculated using four atlases (three histological, one functional). CBP results using newer data and methods were still remarkably similar to the original CBP parcellation results. Across atlases, a consistent hierarchy was observed: HIPS-THOMAS performed best, followed by TDI, ODF, and CBP (Kendall’s W = 1.00, p = 0.007). Histological atlases showed strong mutual agreement (Pearson r = 0.71–0.85), whereas the Zhang atlas demonstrated lower concordance (Pearson r = 0.51–0.63). Despite methodological advances, CBP remains constrained in its ability to delineate thalamic nuclei with histological accuracy. By contrast, structural and diffusion microstructural approaches provided better nuclear localization. These findings highlight the need for hybrid workflows that integrate structural and diffusion-based information to enable more reliable thalamic segmentation for neuroscience research.

Assessing body position through experimental cremation: A pilot study using colorimetry and FTIR-ATR analyses

by Paula Becerra Fuello, Javier Lescure, Aaron Lackinger, María Sedeño Ráez, Jesús Gámiz Caro, Gonzalo Aranda Jiménez

This pilot study evaluates the feasibility and limitations of a multi-proxy approach for identifying potential indicators of horizontal positioning in cremated heads from archaeological, and to a lesser extent, forensic contexts. Two outdoor experimental cremations using fleshed and dry pig crania were conducted to evaluate the influence of pre-burning condition, vertical placement within the pyre and pyre dynamics on the expression of lateralised burning patterns. Combining macroscopic observations, fragmentation, colorimetric and Fourier-Transform Infrared Spectroscopy in Attenuated Total Reflectance (FTIR-ATR) mode, our preliminary observations suggest that lateralised differences in thermal exposure may be detectable under certain conditions. Significant differences (p-value 

Toward a fully wireless endovascular neural interface: Evaluating power transfer efficacy

by Yi-De Tai, Joel Villalobos, Nima Wickramasinghe, Bryce Widdicombe, Ranjith R. Unnithan, David B. Grayden, Sam E. John

Background

Endovascular neural interfaces (ENIs) offer a minimally invasive approach for neural stimulation and recording without the need for open brain surgery. However, current generation devices have long transvascular wires from the implant site to the chest. Eliminating these wires will unlock clinical usability, including lowering infection risk from transvascular wires, reducing the risk of thrombosis from altered hemodynamics, and improving mechanical reliability. However, removing these transvascular wires would require efficient power transfer across the skull and tissue while meeting specific absorption rate (SAR) limits, which is a significant challenge in the field.

Objective

This work designed and evaluated endovascular receiver (Rx) and transmitter (Tx) coils within endovascular geometric and biological constraints to maximize wireless power transfer.

Methods

This study evaluated the optimal operating frequencies, quantified coupling, coil quality factors, power transfer efficiency, and SAR using computational modeling, benchtop, and in-vivo testing. The study also assessed the tolerance to coil misalignment and load mismatch. We evaluated each case with and without ferrites with measurements in air, sheep tissue, and in vivo in sheep.

Results

The results showed that inductive power transfer delivered power to endovascular geometry devices at clinically relevant depths. The maximum power transfer efficiency (PTE) reached 11% at 15 mm and 2% at 30 mm, with up to 72 mW delivered at 30 mm under SAR safety limits. The rectangular planar coil pair performed best at ≤15 mm, whereas the ferrite-core flux-pipe Tx with a helical Rx outperformed beyond ~20 mm and was more tolerant to misalignment.

Conclusion

This study demonstrated the feasibility of wirelessly powering multichannel ENIs using coils that can be placed inside a blood vessel and powered inductively. Making an endovascular neural interface fully wireless has the potential to transform the technology by improving both safety and reliability.

Perceptions of physical and occupational therapists on the utility of surface electromyography data in spinal cord injury rehabilitation

by Nadeen Al Awamry, Laura Seidelin, Alyssa Marino, Ethan Evans, Elizabeth Karam, Vishwa Kumar, Kristin E. Musselman, Anita Kaiser, José Zariffa

Purpose

Spinal cord injury (SCI) impacts physical, emotional, and social well-being, contributing to decreased quality of life and increased healthcare burden. Surface electromyography (sEMG), a non-invasive tool for measuring muscle activity, has demonstrated potential as a biomarker for recovery in SCI research, yet remains underutilized in clinical practice. Understanding how physical therapists (PTs) and occupational therapists (OTs) perceive the use of sEMG is necessary for integrating sEMG into post-SCI treatment and advancing personalized rehabilitation.

Materials and methods

A cross-sectional, qualitative descriptive design was employed. Ten participants (9 PTs and 1 OT) were recruited through convenience sampling. Semi-structured interviews were conducted and analyzed inductively using a thematic analysis approach.

Results

Two major themes were identified: 1) Perceived value of the use of electrophysiology and sEMG data in clinical practice. Participants valued sEMG as an adjunct assessment tool for providing objective feedback after incomplete SCI and setting goals during treatment. 2) Barriers and facilitators to implementing sEMG. Key barriers highlighted include the lack of training and standardized protocols. Continued training, resources, and educational support were key facilitators.

Conclusion

PTs and OTs perceive sEMG as a valuable tool in SCI rehabilitation, but desire education and standardized protocols to support its clinical integration.

Prevalence, outcomes, and predictors of mortality among adult intensive care unit patients with sepsis at a Tertiary Hospital in Tanzania: A prospective cohort study

by Atala Jongo, Edwin Lugazia, Salehe Mrutu, Amina Abillah Omari, Hassani Msanga, Ansbert Sweetbert Ndebea, Felix Paul Amani

Background

Sepsis continues to pose a significant global health challenge, particularly in low- and middle-income countries, which face a disproportionate burden of sepsis and sepsis-related deaths. The estimated prevalence of sepsis and sepsis-related mortality is higher in intensive care units than in hospitals overall. The burden can be higher in tertiary referral centers that receive patients from different regions.This study aimed to determine the prevalence of sepsis, its outcomes, and the factors associated with these outcomes among adult patients admitted to the Intensive Care Unit (ICU) of the Muhimbili National Hospital (MNH) in Tanzania.

Methodology

This prospective cohort study was conducted over a period of six months from May 16 to November 16, 2023, at MNH. A total of 248 patients were admitted during the study period and screened for sepsis on admission or for the development of sepsis during their ICU stay. Sepsis was defined according to the Sepsis-3 criteria as a suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥2 within 24 h of ICU admission. Proportions were used for descriptive statistics, and modified Poisson regression analysis was used to identify independent predictors of mortality at a 95% confidence interval, with P  Results

The prevalence of sepsis was 41.5%. The respiratory system was the most common source of infection (32%), and 22.3% of patients had more than one infection site. The ICU mortality rate was 55.3%, with 35% of patients developing systemic complications during their ICU stay.Factors independently associated with mortality included multiple comorbidities (aPR 3.35, 95% confidence interval [CI], 1.20–9.32; p = 0.021) and a higher SOFA score (aPR 7.08, 95% CI 3.48–14.4; p  Conclusion

This study revealed a high prevalence of sepsis and sepsis-related mortality in the ICU. A high SOFA score and multiple complications were independent predictors of mortality. Early initiation of antibiotic therapy was an independent predictor of survival. This underscores the importance of early treatment, close monitoring, and aggressive management in patients with predictors of poor outcome.

Dialogic reading at age 2 is linked to frontal activation related to executive function at age 5: An fNIRS study

by Ming Yean Sia, Chia-Feng Lu, Ovid J. L. Tzeng, Shinmin Wang

This study investigates the relationship between children’s dialogic reading (DR) experiences with parents at age 2 and their frontal neural responses related to executive function (EF) at age 5. To assess how the intensity of DR influences brain development, we quantitatively measured parental engagement in DR when children are at 2 years of age. Neural activations in frontal regions associated with EF were evaluated using functional near-infrared spectroscopy when children reached age 5. Our results reveal a significant positive correlation between parental dialogic interaction during shared book reading at age 2 and the activation of key brain regions related to EF – the bilateral dorsolateral prefrontal cortex and the bilateral inferior frontal gyrus – during a Dimensional Change Card Sort (DCCS) task at age 5. This correlation persisted even after controlling for maternal education and children’s expressive vocabulary, indicating a robust relationship between early DR experiences and subsequent neural correlates of EF. The results suggest that early DR may help cultivate the neural infrastructure necessary for EF development. By focusing on DR at a young age and assessing neural activity during a classic EF task, the DCCS, our findings contribute additional evidence regarding the role of DR in shaping neural development associated with EF. These results highlight the importance of encouraging interactive DR practices in early childhood, as they not only support language development but also strengthen the neural pathways crucial for cognitive skills essential for academic success.

Co-design of a model for learning conversations about ongoing patient care between medical supervisors and trainees in the rural generalist settings: A research protocol

by Linda Furness, Janani Pinidiyapathirage, Matthew French, James Ware, Liam Weber, Brendan Carrigan

Introduction

In rural generalist clinical settings, medical trainees routinely assess patients and discuss their findings with supervisors to plan ongoing care. These interactions termed ‘learning conversations’, serve as important opportunities for workplace-based learning and clinical decision making. However, preliminary evidence and stakeholder feedback indicate a lack of shared understanding regarding how these conversations should be structured, facilitated, and optimised. This study aims to observe current practices, identify supervisor and trainee learning needs, and co-design a model of learning conversations that enhances educational value and supports safe, effective patient care.

Methods and analysis

This study will use an exploratory sequential mixed methods design structured around the 3Cs of co-design (Co-define, Co-design, Co-refine). Phase 1 (co-define) will involve qualitative observation and audio-recording of learning conversations across two rural hospitals to characterise current practice and inform a protype model. In Phase 2 (co-design), supervisor and trainee focus groups will explore perceived needs, expectations, and feedback on the prototype model. A national online survey of rural supervisors and trainees will further inform model refinement. Phase 3 (co-refine) will incorporate national stakeholder input through a workshop, followed by feasibility testing of the refined model during a pilot simulation at a Rural Clinical School. Outcome data will focus on model usability, perceived relevance, applicability across contexts, and users’ experiences of employing the model during simulated learning conversations.

Discussion

This study will produce a stakeholder-informed model that responds to the specific learning and clinical needs of rural generalist practice. By embedding co-design throughout the research process, the resulting model is expected to strengthen learning conversations, optimise trainee learning, and enhance the quality and safety of patient care. The findings have potential applicability across broader health professional training contexts and can support workforce development in rural healthcare settings.

Sensing nature in the city: The role of sight and sound in restorative tropical urban green spaces

by Juliana Ju Yun Hoo, Shumetha Sidhu, Kok Wei Tan

Rapid urbanization has increased disconnection from nature, especially in cities. While research on restorative environments has largely focused on non-tropical regions, little is known about the restorative potential of tropical urban green spaces (UGSs). This study assessed the perceived restorativeness of tropical UGSs in Malaysia using 120 environmental stimuli from nature, urban, and mixed urban-nature settings. 87 participants were randomly assigned to one of the three modalities: audio-only, visual-only, or bimodal. Each participant rated a subset of 30 stimuli on perceived restorativeness. Results showed that nature and mixed urban-nature scenes were in general rated as more restorative than urban scenes. An interaction effect indicated that, in the visual-only modality, mixed urban-nature scenes were perceived as more restorative than nature scenes, while no significant differences were observed in the audio-only and bimodal modalities. Moreover, perceived restorativeness for nature scenes was comparable across bimodal, visual-only, and audio-only presentations. These findings suggest that small pockets of urban nature (e.g., tree-lined streets, rooftop gardens) can offer greater psychological restoration than wild, untamed forests. In addition, high-quality nature sounds (e.g., birdsong, flowing water) can provide restorative benefits comparable to visual exposure when access to green views is limited. Such insights can inform urban planning strategies to design more restorative and liveable cities.

Stability of the two enveloped viruses NDV LaSota and YF-ZIKprM/E to support process development

by Sven Göbel, Lennart Jacobtorweihe, Max-Leopold Rössig, Frauke Braatz, Fabien Perugi, Yvonne Genzel, Udo Reichl

Building on the established use of enveloped viral vectors, like lentivirus and vesicular stomatitis virus, we investigated the stability of the oncolytic Newcastle disease virus LaSota strain and the chimeric construct of a Zika vaccine candidate YF ZIKprM/E. These vectors are currently being developed for the treatment of solid tumors, such as melanoma and glioblastoma, and for vaccine initiatives, respectively. Virus stability is a critical attribute during cell culture-based virus production and also relevant for downstream processing, storage of the produced material, final vaccine storage and shelf life. Therefore, temperature and pH stability were tested as important parameters during upstream processing and freeze-thaw cycles were tested in context of laboratory-analytics. In this study, both viruses exhibited strong stability of the infectious virus titer when subjected to repeated freeze-thaw cycles. However, exposure to temperatures above 22°C substantially reduced the infectious titers, indicating sensitivity to elevated temperatures. To improve viral stability during storage, we investigated the use of sucrose as a stabilizing excipient. While this did not result in significant improvements for YF-ZIKV, an extended half-life for NDV at room temperature was observed. The observed half-life values of upstream material from NDV of 2.6 h and 2.8 h for YF-ZIKV at 37°C demand consideration of changes to the process design, such as the implementation of a perfusion process to enable continuous, cooled virus harvesting.

Effects of local heat on metabolic health, frailty risk, and exercise adaptations in pre-diabetic older adults: Protocol for the Heat and Exercise in Aging as Therapy (HEAT) clinical trial

by Hui-Ying Luk, Casey R. Appell, Fangyuan Zhang, Jarrod Blinch, K. Sreekumaran Nair, Chwan-Li Shen, Danielle E. Levitt

Introduction

Glycemic dysregulation is a hallmark of type 2 diabetes (T2D) and contributes to skeletal muscle (SKM) loss and frailty risk, especially in older adults. Glycemic control and physical function are supported by SKM capillarization and mitochondrial function, and their impairment contributes to T2D development. While high-intensity interval training (HIIT) is a promising intervention, adherence and effectiveness remain concerns for prescribing HIIT among older adults at risk for T2D. Local heat therapy (LHT) may be a more practical initial strategy to improve SKM architectural factors and precondition SKM, enhancing physiological adaptations to exercise in this population.

Methods and analysis

Heat and Exercise in Aging as Therapy (HEAT) is a two-phase, randomized, sham-controlled clinical trial investigating the efficacy of LHT to improve glycemic control and decrease frailty risk via improved SKM architecture among older adults with prediabetes. LHT is tested as a standalone intervention and as a means to precondition SKM for subsequent HIIT, improving exercise adaptations. In Phase 1, LHT and sham (CON) groups apply heat pads for 90 minutes/day, 6 days/week, for 12 weeks. A separate HIIT group completes 4x4-minute cycling intervals at 90–95% VO₂peak, 3 days/week. In Phase 2, LHT and CON groups begin HIIT. Participants (≥50 years) have impaired fasting glucose (100–125 mg/dL) and/or HbA1c (5.7–6.4%). Biospecimen collection and clinical assessments occur at baseline (T1), after Phase 1 (T2), and Phase 2 (T3). To our knowledge, this is the first study to determine the use of local heat pad on pre-diabetic older population. If successful, LHT may be a practical, scalable, non-invasive intervention to improve glycemic control and reduce frailty risk in older adults with prediabetes, preventing progression to T2D.

Kidney dysfunction is associated with mortality, adverse CT-based muscle metrics, and functional decline in surgically treated liposarcomas of the extremities and trunk

by Julian Kylies, Fabian Haas, Anna Duprée, Tobias B. Huber, Karl-Heinz Frosch, Matthias Priemel, Dominik Kylies

Background

Liposarcomas (LS) of the extremities and trunk are aggressive soft-tissue sarcomas and surgical resection combined with multimodal therapy represents the cornerstone of curative treatment. Despite advances in surgical and medical management patients are still at risk of developing medical complications that negatively affect morbidity and mortality. Kidney dysfunction, sarcopenia and progressive loss of visceral adipose tissue have emerged as prognostically relevant and potentially treatable complications in surgical oncology. However, despite their growing relevance, little is known about their frequency and impact on survival and morbidity in the context of LS.

Methods

We conducted a retrospective study of 47 adult patients with localized LS of the extremities and trunk who underwent curative-intent surgery. Kidney function, CT morphometry of muscle (skeletal muscle index, SMI) and visceral adipose tissue (VAT) as well as clinical assessments including ECOG score were recorded at diagnosis (t1) and after a median follow-up (t2) of 11 months. Kidney dysfunction, defined as a decrease in eGFR of ≥ 25% between time points, was analyzed in relation to survival, sequentially assessed CT-morphometry of muscle and adipose tissue as well as functional status assessed by ECOG scores.

Results

All patients underwent curative-intent surgical treatment with or without additional multimodal treatment (surgery only: 51.1%, additional radiation: 31.9%, additional chemotherapy: 38.3%). Kidney dysfunction was frequent in our cohort (53.2% of all patients) and significantly associated reduced overall survival in Kaplan–Meier, uni- and multivariate Cox proportional hazards regression models (multivariate hazard ratio: 6.7; p = 0.03). In addition, patients with kidney dysfunction experienced a significantly accelerated loss of SMI (p  Conclusions

To our knowledge, this is among the first studies to investigate kidney dysfunction and its consequences in adult LS patients. In our cohort of surgically treated adult patients with LS of the extremities and trunk, kidney dysfunction was a frequent and clinically impactful complication. It was significantly associated with decreased overall survival, loss of muscle and adipose tissue in sequential CT morphometry assessments and progressive functional decline. Off note, CT-morphometry enabled objective, high-resolution tracking of body composition decline and may serve as a promising additional tool for risk stratification. Nonetheless, given the limited cohort size and retrospective single-center design, the generalizability of our findings is limited and the results should therefore be interpreted with caution. Despite these limitations, our findings call for future prospective studies and an awareness for heightened renal surveillance and integrated body composition assessments in the multimodal management of sarcoma patients.

Multidisciplinary Offloading for Healed Diabetic Foot Ulcers: A Prospective Study on Functional Outcomes and Predictors of Recurrence, Amputation, and Mortality

ABSTRACT

To evaluate the effectiveness of multidisciplinary offloading versus standard care on one-year diabetic foot ulcer recurrence, amputation, mortality, and functional recovery. In this prospective cohort study, 232 patients with healed diabetic foot ulcers were stratified into a control group (76 patients) or an intervention group (156 patients) receiving offloading modalities ranging from felt padding to custom-made therapeutic footwear. Assignment was based on shared decision-making considering biomechanical needs and economic feasibility. Primary outcomes included recurrence, amputation, and mortality. Secondary outcomes assessed quality of life, working ability, and ankle function. The intervention group demonstrated significantly lower recurrence (10.9% vs. 25.0%; p = 0.007) and mortality (3.2% vs. 14.5%; p = 0.004). Multivariable analysis identified offloading as independently protective against recurrence (odds ratio 0.35) and mortality (odds ratio 0.24). Amputation rates did not differ significantly after adjustment. Functionally, the intervention group achieved superior recovery in quality of life, working ability, and ankle scores (p < 0.001). Subgroup analysis indicated that customized therapeutic footwear yielded the lowest complication rates and highest patient satisfaction. Multidisciplinary offloading significantly reduces recurrence and mortality while restoring physical function. Although financial barriers influence device selection, customized therapeutic footwear offers the optimal balance of biomechanical protection and functional outcomes.

Effects of a Computational Fluid Dynamics‐Based Mobile Education Program on Syringe‐Based Wound Irrigation

ABSTRACT

The study aimed to develop a computational fluid dynamics-based mobile wound irrigation education program and explore changes in irrigation pressure control, wound irrigation-related knowledge and performance confidence in syringe-based wound irrigation. This study used a single-group pre–post design. A computational fluid dynamics-based mobile wound irrigation program was developed following the Analysis, Design, Development, Implementation, and Evaluation model. The program enabled learners to manipulate irrigation variables and visualize pressure distribution in real time. Thirty-four participants were recruited. Irrigation pressure was measured using a load cell-based device, and knowledge and performance confidence were assessed pre- and post-intervention. Data were analysed using paired t-tests and content analysis. The mean irrigation pressure increased significantly, although the post-intervention mean remained below the recommended pressure range and the proportion of participants achieving the recommended range rose from 0% to 44%. Knowledge and performance confidence also improved significantly. Qualitative findings indicated enhanced understanding of performance standards, improved technical awareness and reduced uncertainty during skill execution. Participation in the computational fluid dynamics-based mobile education program was associated with improvements in irrigation pressure control, related knowledge and performance confidence in syringe-based wound irrigation. These findings should be interpreted as preliminary because of the single-group pre–post design. Numerical visualization and real-time feedback may be useful educational strategies for facilitating the transition from experience-based skill performance to data-driven practice.

Trial Registration: Clinical Research Information Service (CRIS), Republic of Korea: KCT0011256.

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Randomised, double-blind clinical trial protocol to evaluate whether early and perioperative tranexamic acid administration reduces transfusion rates and blood loss of patients undergoing hip fracture surgery in Spain

Introduction

In patients with a hip fracture, anaemia has been associated with increased transfusion requirements, poor functional outcomes, prolonged hospital stays and increased mortality. While anaemia in elderly patients with hip fractures has traditionally been attributed to bleeding during or after surgery, many of these patients are anaemic on hospital admission. Thus, detecting and managing anaemia in the perioperative, postoperative and, most significantly, the preoperative period is important to avoid the need for blood transfusions and to improve patient outcomes. The protocol for this clinical trial is designed to evaluate the efficacy and safety of both combined intravenous and topical tranexamic acid (TXA) therapy, or topical administration alone, assessing its effect on blood loss and the need for blood transfusions in elderly patients undergoing hip fracture surgery.

Methods and analysis

This is a multicentre, double-blinded, randomised, placebo-controlled trial with a 1:1 allocation ratio. Patients of both sexes, aged ≥65 years, who are admitted to the emergency department and will undergo hip fracture surgery are eligible for enrolment. Eligible patients who provide their consent will be stratified according to the type of fracture (intracapsular and extracapsular) and whether or not they are suitable for intravenous TXA therapy, and they will then be randomly allocated to receive either TXA or a placebo. The primary outcome is the blood transfusion rate from patient admission to the emergency department until discharge, while the secondary outcomes include: the preoperative, perioperative and postoperative haemoglobin and haematocrit levels; the preoperative and postoperative occult and total blood loss; the mean length of hospital stay; and any adverse events assessed for up to 1 year after patient discharge.

Ethics and dissemination

The study was approved by the Basque Country Ethics Committee (Ref.: 2021012) and the Spanish Agency for Medicines and Healthcare Products (Agencia Española de Medicamentos y Productos Sanitarios). All participants will provide their written informed consent prior to study inclusion. The trial’s results, regardless of its outcomes, will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals, and they will be made publicly available through the European Union Clinical Trials Register after the end of the clinical trial.

Trial registration numbers

EudraCT Number 2020-002144-23; EUCT Number 2024-519349-31-00.

Effect of a culturally adapted heart-healthy diet with phytosterols and/or krill oil on lipid-related outcomes in familial hypercholesterolaemia: protocol for a multicentre randomised controlled trial in Brazil

Introduction

An affordable heart-healthy dietary approach is essential for the management of familial hypercholesterolaemia (FH); however, the optimal dietary pattern and the role of adjunctive nutrient supplementation remain uncertain. This study aims to evaluate the effects of the Brazilian Cardioprotective Diet (DICA Br), adapted from the Portfolio Diet, with or without phytosterol and/or krill oil supplementation in individuals with probable or definite FH according to the Dutch Lipid Clinic Network (Dutch MEDPED) criteria.

Methods and analysis

The DICA-FH study is a national, multicentre, randomised, factorial, parallel-group, superiority, placebo-controlled clinical trial with a 1:1:1:1 allocation ratio. Participants aged ≥16 years receiving age-appropriate lipid-lowering therapy will be randomised into four groups: (1) adapted cardioprotective diet (DICA-FH) plus phytosterol placebo and krill oil placebo; (2) DICA-FH plus phytosterol 2 g/day and krill oil placebo; (3) DICA-FH plus phytosterol placebo and krill oil 2 g/day or (4) DICA-FH plus phytosterol 2 g/day and krill oil 2 g/day. All participants will undergo whole-genome sequencing and receive appropriate genetic counselling. Primary outcomes will be means of low-density lipoprotein cholesterol and lipoprotein(a) levels after 120 days. Secondary outcomes will include additional lipid biomarkers, adherence to protocol and adverse events. The planned sample size is 300 participants. Follow-up is expected to conclude in July 2026.

Ethics and dissemination

This study was registered under CAAE 65549622.2.1001.0060 and received ethical approval from the Hcor Research Ethics Committee (approval number 5.805.072) and the Brazilian National Research Ethics Commission (CONEP; approval number 6.864.951). Written informed consent will be obtained from all participants prior to enrolment. The study findings will be disseminated through peer-reviewed publications, scientific conferences and channels aimed at the general public.

Trial registration number

NCT06331195.

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