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Impact of indispensable amino acid supplementation on gut function in children at high risk of environmental enteropathy: protocol for an international coordinated group of randomised controlled trials

Por: Lee · G. O. · Owino · V. · Baquiran · A. F. P. · Pasanna · R. M. · Achoribo · S. E. · Meskini · T. · Amadi · B. · Maleta · K. M. · Gaudichon · C. · Serafico · M. E. · Hegde · S. · Cabanilla · C. V. D. · Devi · S. · El Mzibri · M. · Brouwer · A. F. · Kurpad · A. V. · Kelly · P. · Morrison
Introduction

Environmental enteropathy (EE) is a syndrome affecting the gut characterised by villus blunting, reduced nutrient absorption and microbial translocation in children and adults experiencing a high burden of enteric infection due to inadequate access to clean water and sanitation.

Methods and analysis

We will conduct coordinated randomised controlled trials in six countries to determine if supplementation with indispensable amino acids (IAAs) can improve intestinal barrier dysfunction in six geographically diverse populations of 18–36 months old children with stunting or severe stunting. All trials will measure the same primary outcomes while secondary outcomes will be measured on a per-trial basis using standardised protocols across the project. The primary endpoint will be change in gut permeability as assessed by the lactulose/rhamnose ratio. Secondary endpoints include changes in amino acid and carbohydrate absorption using novel, isotope tracer tests. Other prespecified outcome measures include changes in EE biomarkers and child weight. IAA supplementation will be given daily for 28 days and evaluation of the major endpoints will be at baseline and after 28 days of supplementation.

Ethics and dissemination

Ethical approval will be obtained from the Research Ethics Committee at each participating site. Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and face-to-face meetings with participant caregivers.

Trial registration number

CTRI: CTRI/2024/06/069187 (India); ClinicalTrials.gov (NCT06617130, Malawi; NCT06676215, Philippines and NCT07256028, Morocco); Ongoing (Zambia); Ongoing (Morocco); PACTR: (PACTR202311714091884, Ghana).

The world according to girls: a qualitative study of school, work and identity among adolescent girls and young women living with HIV in Ghana

Por: Bhagavathi · V. · Martyn-Dickens · C. · Owusu · S. A. · Nettey · G. K. · Bedele · J. · Sarfo · A. D. · Munyikwa · M. · Moyer · C. A. · Enimil · A. K. · Ratner · L.
Background

Adolescent girls and young women (AGYW) living with HIV in Ghana face multiple intersecting forms of marginalisation. Beyond the clinical management of HIV, little is known about how they construct meaning, navigate identity and imagine their futures within structural contexts shaped by stigma, gender inequity, economic precarity and colonial legacies.

Objective

To explore how AGYW living with HIV in Ghana understand and negotiate their social identities in work and school. We then aimed to understand how their lived experiences at school and work are shaped by broader systems of power.

Methods

This qualitative study drew on semi-structured interviews with AGYW (ages 11–24, n=24) receiving HIV care in Kumasi, Ghana. Data were coded both inductively and deductively. Themes were interpreted through the Ghanaian context using intersectionality, Critical Disability Studies, spoiled identity theory and African feminist decolonial theory. The analysis was conducted iteratively and reflexively, with attention to positionality, gender and structural power dynamics.

Results

Seven major themes were identified: (1) social support; (2) concrete plans for the future; (3) unattainability of the future; (4) coping via detachment; (5) need for privacy and confidentiality; (6) role as an arbiter of HIV information; and (7) financial stress. Across these themes, AGYW described dynamic processes of identity negotiation, moral and emotional labour and structural constraint. HIV was rarely the sole barrier. Rather, it intersected with gender norms, family dynamics, age hierarchies, economic marginalisation and misinformation to shape participants’ social worlds. Some participants coped through detachment or concealment, while others reclaimed agency through caregiving roles, education or aspirational goals.

Conclusions

AGYW living with HIV in Ghana are not only navigating a chronic illness but also resisting a layered matrix of social and structural injustice. Their stories reveal both vulnerability and strategic agency. Interventions and policy must go beyond biomedical care to address stigma, provide confidential and affirming school and work environments, and offer structural supports for emotional, educational and economic well-being.

Comparison of immunity-boosting regimens for COVID-19 upon initiation of immunosuppressive therapy (CIRCUIT): study protocol for a randomised, controlled clinical trial

Por: Carey · D. L. · Ahlenstiel · G. · Brilot · F. · Brown · D. A. · Bull · R. · Crowther · H. · Cunningham · A. · Davenport · M. P. · Diamond · P. · Hamad · N. · Johnston · A. · Kelleher · A. D. · Lee · F. J. · Matthews · G. V. · Petoumenos · K. · Quichua · G. C. · Swaminathan · S. · Trotman
Introduction

Immunosuppression is associated with an increased risk of delayed SARS-CoV-2 viral clearance, severe COVID-19 and related death. This heterogeneous group of affected patients includes but is not limited to those with a haematological malignancy, people on immunosuppressive therapy for the treatment of autoimmune/inflammatory diseases and those following bone marrow transplantation (BMT). Immunosuppression is associated with decreased rates of anti-spike IgG seroconversion following COVID-19 vaccination. While clinical guidelines have been established to guide vaccination pre-splenectomy and post-BMT, there are limited data to guide timing of COVID-19 or other booster vaccines in adults commencing new or intensified moderate to severe immunosuppression. The comparison of immunity-boosting regimens for COVID-19 upon initiation of immunosuppressive therapy (CIRCUIT) study was designed to address this knowledge gap. CIRCUIT investigates whether administration of a third (or subsequent) COVID-19 booster vaccine ≤2 weeks prior to immunosuppression provides greater anti-spike IgG-mediated immunity than a booster given 24 weeks after new or intensified immunosuppression, that is, week 24 timepoint (Group 1; n=280). Additionally, the research will investigate whether giving a fourth post-BMT COVID-19 booster vaccine at 9 months post-transplant provides greater anti-spike IgG-mediated immunity than a booster given 15 months post-transplant (Group 2; n=40).

Methods and analysis

The CIRCUIT study is an open-label, multicentre randomised clinical trial. Participants will be randomised 1:1 to receive either an additional COVID-19 booster ≤2 weeks pre-immunosuppression and a diphtheria/tetanus toxoids (DT) booster at 24 weeks following new or intensified immunosuppression (week 24 timepoint) or receive a DT booster ≤2 weeks pre-immunosuppression and an additional COVID-19 booster at week 24 (Group 1). Group 2 participants who underwent autologous or allogenic BMT in the last 9 months will be randomised 1:1 to either receive a fourth post-BMT COVID-19 booster at 9 or 15 months post-transplant. The primary outcome will be the integrated time-weighted area under the curve anti-SARS-CoV-2 neutralising antibody (NAb) response over 12 months from a SARS-CoV-2 booster as assessed by a high-throughput SARS-CoV-2 NAb platform assay. Key secondary outcomes of the CIRCUIT randomised control trial will include safety and generation of SARS-CoV-2 antigen specific T and B cell responses.

Ethics and dissemination

The research protocol was approved by the Western Sydney Local Health District Human Research Ethics Committee on 25 August 2022 (Ref no. 2022/PID00782 – 20022/ETH0069). Study results will be published in peer-reviewed medical journals and presented at local and international conferences. All findings regardless of the outcome will be reported.

Trial registration number

NCT05415267.

Rehabilitation intervention to improve Recovery after an Episode of Delirium in adults over 65 years (RecoverED): a multicentre, single-arm feasibility study in NHS acute hospitals in the UK

Por: Allan · L. · Um · J. · OConnell · A. · Raghuraman · S. · Bingham · A. · Laberick · A. · Chandler · K. · Connors · J. · Mahmoud · A. · Hawton · A. · Goodwin · E. · Morgan-Trimmer · S. · Goodwin · V. A. · Ukoumunne · O. C. · Jackson · T. A. · Richardson · S. J. · Collier · L. · Glasby · J.
Objectives

To test a theory-informed, person-centred rehabilitation intervention for older adults following a hospital admission complicated by delirium, developed in line with the Medical Research Council framework for complex interventions, to determine whether: (a) the intervention is acceptable to individuals with delirium and (b) a definitive trial and parallel economic evaluation of the intervention are feasible.

Design

Multicentre, single-arm feasibility study.

Participants

19 patient (aged >65 years old) and carer pairs were recruited from six National Health Service acute hospitals across the UK.

Intervention

Home-based rehabilitation programme designed to support recovery after hospital discharge, addressing cognitive, physical, physiological and psychosocial needs. Delivered by a trained team of occupational therapists, physiotherapists and rehabilitation support workers, the intervention included a comprehensive home assessment, collaborative goal setting, up to 10 personalised sessions over 12 weeks and the use of a recovery record to guide progress, education and psychosocial support.

Outcome measures

Examined aspects of feasibility including eligibility, recruitment, data collection, attrition, acceptability of the rehabilitation intervention and potential to calculate cost-effectiveness.

Results

In total, 419 patients were identified as having delirium and 36 met the full eligibility. 19 patient and carer pairs agreed to participate in the study (consent rate 53%; 95% CI 35% to 70%) with 13 participants going on to start the intervention (68%; 95% CI 43% to 87%) and 10 participants completing final follow-up (53%; 95% CI 29% to 76%). Baseline assessments were conducted either during hospitalisation or postdischarge, with initial assessments occurring a mean of 18 days (SD=13.0) postdischarge, and 77% completed within 14 days. Participants completed a mean of eight sessions (SD=2.9). 19 participants completed the primary outcome at baseline, while 10 participants completed it at 6-month follow-up. The economic evaluation indicated a total cost of £1249.29 per participant, covering assessments, intervention sessions and training costs.

Conclusions

The intervention showed feasibility among older adults recovering from delirium, as evidenced by the trial processes for participants who entered the study. However, recruitment challenges indicate a need for better strategies and further research through a definitive randomised controlled trial to demonstrate the effectiveness and cost-effectiveness of the intervention.

Trial registration number

ISRCTN15676570

Participatory priority setting of research questions for improving hospital care of adults with childhood-onset intellectual disabilities (PRISMA): a study protocol for a mixed-methods study

Por: Scheffel · A. · Fritsch · T. · Arnold · S. · Asam · T. · Bettenhausen · B. · Dengler · B. · einsmehr · V. · Spielmann · J. · Weidmann · A. · Winterholler · M. · Prodinger · B.
Introduction

Persons with childhood-onset intellectual or complex disabilities have an elevated probability of encountering delayed or erroneous diagnoses during hospital treatment. It is imperative to consider the possibility that mistreatment may worsen their health. Persons with intellectual disabilities face numerous challenges in accessing and using healthcare. These challenges include structural and communication barriers, as well as a dearth of competencies among health professionals in interacting with persons with intellectual disabilities. Nevertheless, there is a paucity of studies that analyse the challenges faced by persons with intellectual disabilities in hospital and even fewer that involve persons with intellectual disabilities in the research process. Therefore, the objective of the study described in this protocol is to identify the salient research questions for improving hospital care of adults with childhood-onset intellectual disabilities by collecting and prioritising the different perspectives of patients, caregivers and clinicians.

Methods and analysis

The study design is based on the Priority Setting Partnership procedure of the James Lind Alliance, encompassing four steps to identify and prioritise issues with patients, caregivers and clinicians. Initially, problems and issues pertinent to those affected are collated using an open online questionnaire and subsequently clustered into topics. In the second step, the topics are transformed into potential research questions and reviewed by available scientific literature. Subsequently, research questions that cannot yet be answered by current literature are prioritised by participants in a second online questionnaire. Finally, the 25 questions rated most relevant are to be discussed in a one-day workshop with participants reflective of all target groups. The salient 10 research questions are to be determined using nominal group technique.

Ethics and dissemination

The study has received a positive ethics vote from the Ethics Committee at the Ludwig Maximilian University of Munich in accordance with the Declaration of Helsinki on 21 March 2025 (reference 25-0106). This study’s findings will be shared in academic conferences and published in scientific peer-reviewed journals.

Trial registration number

DRKS00037347.

Improving menstrual and vaginal health for all (IMVAHA): protocol for a randomised cross-over trial assessing the impact of menstrual products on the vaginal microbiome of women aged 18-35 years in Cameroon, Peru and Switzerland

Por: Ticlla · M. R. · Dumbaugh · M. · Condori-Catachura · S. · Kenfack · J. · Hattendorf · J. · Van Der Donck · L. · Arista · K. M. · Arora · N. · Gebert · S. · Ackermann · L. · Ahannach · S. · Riveros · M. · Blas · M. M. · Kenmoe · S. · Barriere · F. Y. · Shea · A. A. · Pinedo-Cancino · V.
Introduction

Menstrual health is critical to achieving gender equity and reaching the 2030 Sustainable Development Goals, yet evidence on the health impacts of menstrual products—particularly on the vaginal microbiota—is limited. The Improving Menstrual and Vaginal Health for All (IMVAHA) project aims to address this knowledge gap through qualitative exploration, a health survey and clinical trial embedded in three sister projects: Laura (Peru), Leke (Cameroon) and Marie (Switzerland). This paper outlines the protocol for the IMVAHA health survey and clinical trial studies, which aim to (1) assess menstrual hygiene practices, product preferences and vaginal health; and (2) evaluate longitudinal changes in vaginal microbiota associated with the use of pads, tampons and menstrual cups.

Methods and analysis

The IMVAHA project will take place in urban Cameroon, urban Peru, and in Switzerland. The baseline survey will explore vaginal and menstrual health behaviours and preferences, including vaginal complaints, menstrual products and menstrual stigma. Descriptive statistics will be calculated for a cross-sectional profile of vaginal and menstrual health within and between contexts, and mixed effects linear regression models will be run to identify associations between contextual factors and key vaginal and menstrual outcomes. From survey participants, 300 eligible, consenting women (100 per country) will be enrolled in a 7-month crossover clinical trial. As a self-controlled trial, a dedicated control group is not necessary. Each participant will use pads, tampons and menstrual cups for two menstrual cycles per product, providing vaginal swabs at baseline and post-menstruation. Swabs will undergo 16S rRNA sequencing, pH testing and screening for toxic shock syndrome-related bacteria. A short survey on health behaviours and symptoms, menstrual hygiene practices and participant experiences with different menstrual products will be administered during each menstrual period. The primary outcome of the clinical trial is the log ratio of Dialister to Lactobacillus crispatus abundance measured after the use of different menstrual products. Mixed-effects linear regression will assess differences in the primary outcome across product types. Secondary analyses will include per-protocol comparisons and ORs with 95% CIs.

Ethics and dissemination

The study complies with the Declaration of Helsinki, Council for the International Organizations of Medical Sciences guidelines and local regulations. Ethical approval has been obtained in all three countries (National Ethics Committee for Human Health Research in Cameroon (CE N° 2024/03/1649/CE/CNERSH/SP); the Institutional Review Board of the Universidad Peruana Cayetano Heredia and Universidad Nacional de la Amazonía Peruana in Peru (217572) and the Ethics Commission of Northwest and Central Switzerland (2024-02135)). Informed consent will be obtained from all participants after detailed explanation of study procedures and risks. Data will be securely stored, with participant anonymity maintained. A political economy analysis will explore regulatory environments for menstrual products, and findings will be disseminated through policy briefs, stakeholder networks, academic publications and conferences.

Trial registration number

NCT06646185.

Midodrine for Sepsis Treatment and Early Vasopressor Weaning (MID-STEP): protocol for a pragmatic randomised clinical trial

Por: Tekin · A. · Halpern · G. · Gowda · D. · Bansal · V. · Schuchard · A. · Joguncic · A. · Schulte · P. · Odeyemi · Y. E. · Ahmad · S. · Madsen · B. · Rizwan · Z. · Barreto · E. F. · Reddy · S. · Bhavsar · V. · Sanghavi · D. · Domecq Garces · J. P. · Khan · S. A. · Shiari · A. · Cartin-Ceba
Introduction

Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use.

Methods and analysis

A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing.

Ethics and dissemination

The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations.

Trial registration number

NCT06319248.

ProHealth: a co-designed online home-based healthy eating and exercise programme for men with prostate cancer treated with androgen deprivation therapy - a study protocol for a feasibility and preliminary efficacy randomised controlled trial

Por: Baguley · B. · Daly · R. · Livingston · P. · Rawstorn · J. · White · V. · Koorts · H. · Fraser · S. · Gardner · J. · Atkins · L. · Steer · B. · O · E. · Heneka · N. · Abbott · G. · Russell · G. · McNamara · G. · Kiss · N.
Background

Androgen deprivation therapy (ADT) improves survival in advanced prostate cancer but may lead to debilitating side effects, including sarcopenic obesity and a 10–45% increased risk of other comorbidities. Guidelines recommend exercise and nutrition interventions during ADT, but access to these services is often limited, and referral pathways are unclear. This study aims to evaluate the feasibility and preliminary efficacy of an online, home-based, multi-faceted, exercise, nutrition and education programme (ProHealth) for men with prostate cancer treated with ADT. ProHealth was co-designed with consumers and healthcare professionals to include (i) education on prostate cancer and treatment-related side effects and (ii) multimedia behaviour change resources to support individualised nutrition and exercise behaviour change.

Methods and analysis

This 12-week randomised controlled trial (target n=50) will include men treated with ADT for >3 months or who have completed ADT in the last 24 months, are overweight or obese and are not under the care of a dietitian or exercise professional. Participants will be randomised (1:1) to the ProHealth intervention or usual care. The intervention group will receive four consultations with an Accredited Practising Dietitian to promote a high protein and energy reduced diet, and five consultations with an Accredited Exercise Physiologist to follow a home-based progressive resistance training and aerobic exercise programme. The primary outcomes are feasibility (recruitment rate, retention, data completeness, reach, safety, consultation attendance and adherence, and usage of the ProHealth web platform), acceptability and satisfaction of the ProHealth intervention. Exploratory secondary outcomes will be assessed at baseline and 12 weeks and include changes in body weight and composition (total and appendicular fat-free mass, fat mass), quality of life (Functional Assessment of Cancer Therapy (FACT)—General, FACT-Prostate, FACT-Fatigue), physical function (30-second sit-to-stand), dietary intake (3-day food diary) and physical activity (7-day accelerometer). Linear regression models will estimate differences between the intervention and usual care group. Qualitative interviews on participant satisfaction will be transcribed verbatim for thematic analysis.

Ethics and dissemination

This study is approved by Deakin University Human Research Ethics Committee (DUHREC2024-038) and registered on Australian and New Zealand Clinical Trials Registry (ACTRN12624000874516). Findings will be disseminated through peer-reviewed journals, scientific meetings and other public forums.

Trial registration number

ACTRN12624000874516.

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Cost-effectiveness of osteoporotic fracture risk assessment in people with intellectual disabilities: a UK NHS modelling study

Por: Png · M. E. · Frighi · V. · Holt · T. A. · Achana · F. · Smith · M. C. · Collins · G. S. · Roast · J. · Petrou · S.
Objectives

We compared the cost-effectiveness of alternative fracture risk assessment strategies for people with intellectual disabilities (ID) aged ≥40 years from a UK National Health Services perspective over a lifetime horizon.

Design

Cost-effectiveness analysis using a lifetime decision-analytical model.

Setting

UK primary care, with data from literature and national databases.

Participants

People with ID.

Interventions

Three strategies were assessed: (S1) Risk assessment using the UK QFracture score; (S2) use of IDFracture (a fracture risk prediction tool specifically developed for adults with ID); and (S3) conducting a one-time dual-energy X-ray absorptiometry (DXA) scan in all. S1 and S2 were followed by DXA scan for those at risk. At-risk individuals received treatment according to UK practice (bisphosphonates plus vitamin D and calcium for osteoporosis, and vitamin D and calcium alone for osteopenia).

Primary outcome measures

Direct healthcare costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER).

Results

In the base case, S2 (ICER: –£2568/QALY) was dominant (ie, less costly and more effective) and S3 (ICER: £1678/QALY) was cost-effective relative to S1 for major osteoporotic fracture (MOF). For hip fracture, S2 (ICER: £32 116/QALY) and S3 (ICER: £49 536/QALY) were not cost-effective relative to S1 under the National Institute for Health and Care Excellence-recommended cost-effectiveness thresholds. Findings from the sensitivity analyses were predominantly consistent with the base-case results. Subgroup analyses showed that age-specific and gender-specific strategies could be used.

Conclusion

For people with ID aged ≥40 years, a proactive approach to risk assessment for MOF is not only clinically beneficial, but also cost-effective.

Association between older patients receiving geriatric co-management at the emergency department and acute hospital admissions compared to usual care: an observational, controlled study in the Netherlands

Por: Hogervorst · V. M. · Ribbink · M. · van Eekelen · R. · Buurman · B. M. · De Jonghe · A. · Macneil Vroomen · J. L.
Objectives

The aim of this study is to determine if a geriatric co-management model, referred to as ‘The Geriatric Emergency Medicine (GEM)-team’ is associated with less admissions to hospital in older patients compared with the usual care without increasing the risk of mortality or 30-day emergency department (ED) readmissions.

Design

This observational, controlled study used 18-month data prospectively collected from hospital records. Inverse probability weighting was used to account for baseline differences.

Setting

An ED at a suburban Dutch general hospital, receiving approximately 10 000 patients aged 70 or older per year.

Participants

All patients aged 70 or older were screened according to predefined criteria. When positively screened patients were presented at the ED on weekdays between 09:00–17:00, they received geriatric co-management. Outside these hours and when the capacity of the GEM team was reached, patients received care as usual.

Interventions

Geriatric co-management at the ED involves a geriatric multidisciplinary team in collaboration with the primary ED physician who share management and responsibility for the provided medical treatment and nursing care starting directly at the primary assessment.

Primary and secondary outcome measures

The primary outcome was hospital admission and secondary outcomes were the composite outcome of 30-day ED readmissions and mortality.

Results

Patients receiving geriatric co-management (n=972) had lower odds for hospitalisation (OR: 0.77, 95% CI 0.65 to 0.91) compared with the control group (n=1355) while 30-day ED readmissions and mortality did not differ between groups (OR: 1.11, 95% CI 0.91 to 1.36).

Conclusions

Geriatric co-management at the ED is associated with decreased hospital admissions while 30-day ED readmissions or mortality was not impacted. These preliminary results contribute to the evidence that geriatric co-management may be an effective intervention for older patients with frailty at the ED.

Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial

Por: Huerta · M. · Lopez-Ben · S. · Llado · L. · Sanchez-Cabus · S. · Mils · K. · Molina · V. · Dopazo · C. · Vidal · L. · Dalmau · M. · Caralt · M. · Roson · N. · Merino · X. · Armario · D. · Salcedo · M. T. · Pellino · G. · Sapisochin · G. · Gomez-Gavara · C. · LIVERGREEN Collaborative Grou
Introduction

Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence.

Methods and analysis

This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years.

Ethics and dissemination

The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences.

EudraCT number

2023–5 08 316-27-00.

Trial registration number

NCT06398028.

Protocol version

V.12, 18 March 2025

Changes in the epidemiology of heart failure in the decade 2014-2023: insights from the AQUORE retrospective cohort study

Por: Lancia · L. · Dante · A. · Caponnetto · V. · Petrucci · C. · Masotta · V. · Mammarella · L. · Romano · S.
Objective

Heart failure (HF) is a major public health issue due to its high morbidity, mortality and healthcare burden. This study aimed to provide estimates of HF incidence, survival rates, outcome changes and their predictive factors in a central Italian population over the decade 2014–2023.

Design

Population-based retrospective cohort study.

Setting

Hospital discharge records from all hospitals in L'Aquila Province of Italy were analysed.

Participants

All residents who experienced a HF index hospitalisation between 2014 and 2023 were included. HF index hospitalisation was defined as the first hospitalisation for HF in patients with no prior hospitalisation from the same diagnosis for at least 4 years.

Primary outcome measures

The primary outcomes were age-standardised and sex-standardised incidence rates of HF index hospitalisations and all-cause mortality following index hospitalisation. Incidence rate ratios (IRRs), survival and their associated factors were analysed with negative binomial regression models, Kaplan-Meier analysis and Cox proportional hazards models, respectively.

Results

A total of 6965 incident cases from 17 588 HF hospitalisations in the decade under study were analysed. The overall standardised incidence rate was 1.73 per 1000 person-years, with significant differences by age and sex. Incidence rates decreased by 17% from 2014–2018 to 2019–2023 (IRR: 0.834; 95% CI 0.743 to 0.936). Cumulative 1-year and 5-year survival were 70.05% and 36.38%, respectively, with a progressively higher mortality risk in older people. Compared with the 2014–2018 cohort, the 2019–2022 cohort showed improved survival at 30 and 90 days and at 1 year overall and by age groups, with

Conclusions

HF incidence declined, particularly in older populations, and remained higher in men, while survival rates improved. Despite these trends, HF continues to represent a substantial clinical and public health burden.

Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) used in ambulatory palliative care for adult patients with cancer in low-income and middle-income countries: a systematic review protocol

Por: Mathew · M. · Ghoshal · A. · Kabukye · J. K. · Shetty · N. · Dhyani · V. S. · Chakraborty · S. · Shetty · D. K. · B · B. · Salins · N.
Introduction

The global burden of cancer is increasingly concentrated in low-income and middle-income countries (LMICs), where health systems face significant challenges such as late-stage diagnosis, limited resources and restricted access to specialised care. Palliative care plays a vital role in improving symptom control and quality of life for patients with cancer, particularly as care delivery shifts toward ambulatory and community-based settings. In this context, patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are crucial for capturing patients’ perspectives on the quality of care. However, the use and characteristics of these instruments in ambulatory palliative care settings within LMICs remain poorly understood. This systematic review aims to identify and map PROMs and PREMs used among adult patients with cancer receiving ambulatory palliative care in LMICs, and to examine their content, psychometric properties and alignment with key domains of quality palliative care.

Methods and analysis

This systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) guidelines. The search will be conducted across seven databases from the database inception to December 2025. Two independent reviewers will screen titles, abstracts and full-text articles using Rayyan software to identify studies involving adults (≥18 years) with cancer in ambulatory palliative care settings. Data extraction will capture study characteristics, instrument content and psychometric properties. The final review will be reported in accordance with the PRISMA-COSMIN for Outcome Measurement Instruments. A narrative synthesis will be conducted, mapping the identified instruments against the eight domains of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care to identify measurement gaps and inform future instrument development. A meta-analysis will be conducted if sufficient homogeneity exists.

Ethics and dissemination

This review will include only published data; therefore, no approval is required. The findings of this review will be presented at conferences and published in an open-access peer-reviewed journal.

PROSPERO registration number

CRD420251273579.

LIFE-UP Day audit to monitor implementation of post-intensive care syndrome prevention practices: a multicentre cross-sectional study in Belgian intensive care units

Por: Rousseau · A.-F. · Khai · N. · DOrio · V. · Fraipont · V. · Gurdebeke · C. · Minguet · G. · Pinck · E. · Verscheure · S. · Wertz · D. · Lambermont · B. · Berger-Estilita · J.
Objective

To evaluate the feasibility and relevance of the LIFE-UP Day audit, a simple, 1-day benchmarking tool based on the multidisciplinary LIFE-UP bundle (Limit sedation, optimise nutritional Intakes, engage Families, promote Exercise and follow-UP the patients after discharge) and assessing the implementation of postintensive care syndrome (PICS) prevention strategies in daily practice.

Design

Exploratory multicentre cross-sectional audit study.

Setting

Eight Belgian adult intensive care units (ICUs), between April and July 2024.

Participants

All patients present at 08:00 on the audit day and hospitalised for ≥24 hours.

Main outcome measures

An independent nurse collected data on sedation, analgesia, nutrition, family empowerment, physical exercise and post-ICU follow-up. A multidimensional LIFE-UP composite score (raw 0–10 points), normalised to a 5-point scale, was created to quantify adherence to PICS prevention practices based on current recommendations. Feasibility was evaluated through data accessibility, resource needs, cooperation of ICU teams and the ability to complete the audit within 1 day. Relevance was evaluated through adherence to the bundle, assessed by comparing LIFE-UP scores between ICUs. Quantitative results were expressed as median and IQR.

Results

The audit was tested in 87 patients aged 68 (59–74) years, 9 (5–15.5) days after their admission. The audit was feasible across all ICUs: necessary data were available, resources required were minimal and cooperation was excellent. The LIFE-UP score highlighted significant variability between ICUs (2.5 (1.75–2.75), p

Conclusions

The LIFE-UP Day audit proved feasible and provides a first structured framework for benchmarking. Broader implementation will be essential to validate the LIFE-UP score, refine the model and ultimately determine whether it can translate into improved patient and family outcomes.

Can a fluorescent imaging device (MolecuLight) function as an adjunct to surgical debridement during revision knee arthroplasty for periprosthetic infection in a tertiary centre: a feasibility study

Por: Archer · J. E. · Adlan · A. · Sumathi · V. · Stevenson · J.
Objectives

Radical surgical debridement is central to the eradication of prosthetic joint infection. Surgeons are taught that the adequacy of debridement is critical to the success of revision procedures. We aimed to assess the feasibility of using a handheld fluorescent imaging device as an adjunct to tissue debridement in the management of periprosthetic joint infection (PJI) after standard radical debridement.

Design

Prospective feasibility trial.

Setting

This was performed at a tertiary prosthetic joint infection unit (The Royal Orthopaedic Hospital, Birmingham, UK), multidisciplinary team (MDT).

Participants

10 patients with established PJI managed through a tertiary prosthetic joint infection MDT were recruited between January 2023 and December 2023. All patients underwent standard management, including radical debridement.

Intervention

After completion of standard radical debridement, the device was used to identify any remaining areas of fluorescence. These areas underwent excision for further intraoperative microbiological and histological sampling to analyse if the represented areas had residual bacterial load.

Primary outcome

To assess whether the fluorescence imaging device is able to detect additional areas of fluorescence which led to positive tissue sampling.

Results

In all cases, the device was able to identify areas of fluorescence, indicating further debridement. In eight cases, an organism was isolated after additional microbiological sampling and culture. In all eight cases, the same isolate was identified with the standard sampling. Additional histological sampling was performed in eight cases and confirmed acute infection in three cases. The remaining five cases demonstrated histologically inflammatory tissue consistent with chronic infection.

Conclusion

This study is encouraging for the feasibility of using this device as an adjunct for debridement in the surgical management of PJIs; further evaluation is underway.

Effects of pronatal policies on sexual and reproductive health services: a protocol for a scoping review

Por: Mburu · G. · Galati · A. · Chou · D. · Genatra · B. · Kiarie · J. · Boydell · V.
Introduction

In the context of declining total fertility rates, many governments are seeking the optimal blend of policy interventions to encourage childbirth. Scholars have mapped how pronatal policy agendas are shaping social policies, yet there has been less attention on how such agendas shape health policies. This review will map and synthesize the evidence on how pronatal policies affect sexual and reproductive healthcare.

Methods and analysis

A scoping review will be conducted using two searches. One search will identify relevant peer-reviewed papers in Medline, EMBASE, social policy and practice, global health and Web of Science databases. A second search will identify relevant grey literature from Overton and Policy Commons databases. Sources will be managed using Rayaan software and studies selected based on specified inclusion criteria. Data will be extracted using a customised extraction form, mapped and subsequently synthesised using narrative approach.

Ethics and dissemination

This review will be disseminated through a peer-reviewed manuscript and conference presentations. Ethics and patient engagement are not required for a scoping review.

PROSPERO registration number

CRD420251156155.

Effectiveness of anaemia interventions in indigenous populations across the globe: a systematic review protocol

Por: Thatoju · P. K. · Mallya · S. D. · Dhyani · V. S. · Shetty · R. S. · Kotebagilu · N. P. · Pattanshetty · S. M. · Bhat · R. G. · Kunder · M. A. · Kumar · A. · Kaur · H. · Poobalan · A.
Introduction

Anaemia is highly prevalent among the indigenous population globally. Several interventions have been used to prevent and manage nutritional anaemia, including dietary measures, health education, oral iron supplements, food fortification and intravenous iron therapy. This protocol describes a systematic review and meta-analysis to assess the effectiveness of interventions for the prevention and treatment of nutritional anaemia in indigenous populations worldwide.

Methods and analysis

The review will include randomised controlled trials, quasi-experimental studies and observational studies evaluating interventions, including but not limited to iron and folic acid supplementation, dietary modifications, food fortification, deworming and health education. A robust search strategy will be developed, and six electronic bibliographic databases and Google Scholar will be searched from 2000 to 2025. Two reviewers will independently screen the identified studies, extract data, conduct a critical appraisal and evaluate quality using the Joanna Briggs Institute tool. Based on the level of heterogeneity, a meta-analysis will be conducted using either a fixed-effect or random-effects model, with pooled estimates, and 95% CIs. The I2 statistic will be used to evaluate heterogeneity. When meta-analysis is not feasible, narrative synthesis will be conducted. The impact of the intervention type and delivery model will be investigated using subgroup analysis.

Ethics and dissemination

This systematic review has been registered with PROSPERO. Ethical approval is not required as the study does not collect primary data from participants. The findings will be communicated via peer-reviewed journal articles and presentations at national and international conferences.

PROSPERO registration number

CRD420251120554.

Connection, confluence and convergence: a protocol for reviewing policies on antimicrobial resistance and plastic pollution

Por: Shah-Rohlfs · R. · Landicho · J. · Endoma · V. · Sornillo · B. J. · Treskova · M. · Rocklöv · J. · McMahon · S. A. · Renosa · M. D. C.
Introduction

Antimicrobial resistance (AMR) and plastic pollution are converging global crises that threaten both human health and environmental sustainability. Despite the growing recognition of these challenges, few legislative and policy frameworks acknowledge the complex interplay between antibiotic misuse and environmental plastic contamination. This protocol seeks to bridge that gap by critically examining policies in Europe and the Philippines, focusing on those that target antibiotic misuse and plastic pollution in human and animal health.

Methods and analysis

Document analysis will be employed to systematically review relevant legislative and policy frameworks. We will retrieve laws, regulations and policy documents from official databases, government websites and other sources using broad inclusion criteria. The extraction process and analysis will be guided by the READ (Ready, Extract, Analyse, Distill) approach which will ensure a thorough examination of how these documents address the dual challenges of AMR and plastic pollution. Particular attention will be paid to identifying policy gaps, overlaps and synergies that may affect the overall effectiveness and coherence of current governmental responses.

Ethics and dissemination

This policy review has been granted exemption from ethical review by the Research Institute for Tropical Medicine (RITM-IRB No. 2024-35), Philippines. The results are expected to provide a robust evidence base to inform the development of integrated policies at the nexus of global public health and environmental sustainability. Findings will be disseminated at academic conferences and peer-reviewed publications and to key stakeholders within European, Philippine, and international organisations.

Trial registration number

The detailed protocol is pre-registered and openly available on the Open Science Framework (https://osf.io/3tkn2/overview).

Development and cross-site validation of machine-learning models for diagnosis and prognosis of stable angina with and without obstructive coronary artery disease: a study protocol

Por: Deng · J. · Patel · S. K. · Fung · M. · Heybati · K. · Layard · B. · Wang · B. · Rubin · B. · Simard · T. · Hibbert · B. · Anderson · T. · Subasri · V.
Introduction

Angina with no obstructive coronary artery disease (ANOCA) affects millions and is frequently under-recognised because diagnostic pathways and risk tools predominantly target obstructive coronary artery disease (CAD). This protocol describes shared methods for two machine-learning (ML) studies: (1) differentiating ANOCA from stable angina with obstructive CAD and (2) predicting long-term mortality among patients with ANOCA and obstructive CAD.

Methods and analysis

We will develop and cross-site validate ML classification models using a multicentre retrospective cohort drawn from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry and institutional datasets from the University of Ottawa Heart Institute and the University Health Network. Eligible participants are adults (≥18 years) undergoing initial cardiac catheterisation for chest pain/anginal equivalents since 1995, excluding prior revascularisation, major structural heart disease and predefined non-anginal indications. Outcomes are (1) ANOCA (0% to

Model development will use nested cross-validation with stratified k-fold inner-loop tuning and leave-one-site-out cross-validation for repeated external validation. Candidate predictors will be harmonised across sites, filtered for missingness and refined using expert/directed acyclic graph-guided selection plus Boruta and Least Absolute Shrinkage and Selection Operator. Preprocessing includes appropriate encoding, missing-data imputation (multivariate imputation by chained equations) and feature scaling. Algorithms will include elastic-net logistic regression, random forest, LightGBM and multilayer perceptron models; hyperparameters will be optimised via Bayesian optimisation. Performance and threshold tuning will be reported. Explainability and subgroup fairness will be assessed using SHapley Additive exPlanations. Final models will be deployed as a web-based clinical risk calculator.

Ethics and dissemination

Ethics approval has been obtained from the University of Calgary and the University Health Network (#24-5916). Analyses will use deidentified data in secure environments; only aggregate results will be reported. Findings will be disseminated via peer-reviewed publications, conferences and a web-based calculator.

Why do older people not adhere to a healthy lifestyle: a qualitative exploration of perceived barriers among older people living in a low-income and middle-income country setting

Por: Jayasinghe · V. · Ferdinando · R. · Abeysena · C.
Objective

To explore perceived barriers to adhering to a healthy lifestyle among older people living in a Sri Lankan setting.

Design

Qualitative thematic analysis of in-depth interviews among older people.

Setting

The study was conducted in Kalutara district, Sri Lanka.

Participants

In total, 28 older people aged between 60 years and 74 years were interviewed.

Results

Six major themes were identified following the analysis. They were named as lack of knowledge, financial difficulties, poor health status, domestic constraints, cultural norms and changing the living environment. Lack of knowledge emerged through two subthemes, namely lack of information and lack of services. Domestic constraints were derived from family commitments and domestic conflicts, while cultural norms came via beliefs and customs. Poor health status emerged through three subthemes, namely disabilities, diseases and polypharmacy, while changing the living environment emerged via adaptation and urbanisation.

Conclusion

This study provides evidence of real-life perceptions on why older people do not adhere to a healthy lifestyle. Barriers are multifaceted and complex, yet those dimensions need to be considered heavily while developing lifestyle programmes to get maximum benefit for the older people.

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