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Polyneuropathy in kidney transplant recipients: a cross-sectional study in Groningen, the Netherlands

Por: Nolte · S. · Moes · H. R. · Bakker · S. J. L. · Oldag · C. · Lange · F. · de Greef · B. T. A. · Nolte · I. M. · Van Londen · M. · Elting · J.-W. J. · Faber · C. G. · Van Doorn · P. A. · Berger · S. P. · Drost · G.
Objectives

To determine the prevalence and clinical characteristics associated with polyneuropathy in kidney transplant recipients (KTRs).

Design

Cross-sectional study.

Setting

SENS study at the University Medical Center Groningen, the Netherlands, December 2021–May 2023.

Participants

KTR, participating in the ongoing TransplantLines Biobank and Cohort Study, ≥12 months post-transplantation.

Main outcome measures

Participants underwent a structured neurological assessment including history taking, neurological examination, quantitative sensory testing and nerve conduction studies. An expert panel classified participants into no/possible, probable/definite large fibre polyneuropathy or small fibre neuropathy. Large-fibre subtypes included axonal or demyelinating, pure sensory, pure motor and sensorimotor. To assess potential associations with clinical characteristics, logistic regression analysis was conducted.

Results

We included 160 KTRs with a mean age of 59.8±11.6 years at a median of 6.1 (95% CI 3.9 to 13.1) years post-transplantation, with 16 KTRs (10%) diagnosed with polyneuropathy before study inclusion. In total, 84 KTRs (53%) were identified with large fibre polyneuropathy and 7 KTRs (4%) with small fibre neuropathy. KTRs with large fibre polyneuropathy presented with either sensor-predominant polyneuropathy (40 KTR (48%)) or sensorimotor polyneuropathy (44 KTR (52%)). We found no neurophysiological characteristics of demyelination. Overall, 18% (95% CI 11% to 27%) of KTRs with large fibre polyneuropathy were asymptomatic. Higher age (OR=1.04 (1.01 to 1.08), p=0.01), male sex (OR=2.55 (1.19 to 5.60), p=0.02), diabetes (OR=5.58 (1.36 to 38.14), p=0.03) and elevated urea levels (OR=1.12 (1.04 to 1.23), p=0.01) were significantly associated with polyneuropathy in KTR.

Conclusions

In contrast with previous studies, axonal sensory or sensorimotor polyneuropathy is highly prevalent and often underdiagnosed in KTR. Next to higher age and male sex, it was independently associated with diabetes and higher urea levels. Further research is needed to reveal the aetiology and course of polyneuropathy in KTRs.

Trial registration number

NCT04664426.

Risk-based selection for carotid revascularisation using the IMPROVE score versus standard care in symptomatic carotid artery disease: a model-based cost-effectiveness analysis using pooled-data

Por: Nies · K. P. H. · Ramaekers · B. · Bierens · J. · Auer · D. P. · Schindler · A. · Saam · T. · Bos · D. · de Jong · P. A. · Nederkoorn · P. J. · de Borst · G. J. · van Oostenbrugge · R. J. · Joore · M. A. · Kooi · M. E. · Smits · L. J. M.
Background

A clinical prediction model (IMPROVE) for ipsilateral ischaemic stroke risk in symptomatic patients with carotid disease was recently developed with good performance. We aim to evaluate the model-based cost-effectiveness of IMPROVE-based triage versus triage in care-as-usual (CAU) for optimal medical treatment (OMT) alone or carotid endarterectomy plus OMT.

Methods

A dataset of 678 patients with carotid disease and a recent ipsilateral ischaemic stroke, transient ischaemic attack or amaurosis fugax from four cohort studies informed a decision-analytic model. Stratification of patients for carotid endarterectomy was based on ≥50% carotid stenosis (CAU arm) or a range of 3-year ipsilateral ischaemic stroke risk thresholds (IMPROVE arm). The threshold resulting in the lowest number of ipsilateral strokes and perioperative strokes and deaths was selected as the optimal threshold. Patients with

Results

IMPROVE-based triage reduced ipsilateral ischaemic strokes and perioperative strokes and deaths by 34.5% (CAU: 4.3%, IMPROVE: 2.8%) over 3 years. Revascularisations decreased by 20% with IMPROVE, while Quality-Adjusted Life Years slightly increased. Procedural stroke occurred in 1.8% of patients in CAU versus 1.4% of patients for IMPROVE. Societal costs decreased on average by 1441/patient for IMPROVE versus CAU for a 3-year time horizon (lifetime cost reduction: 6101/patient). Subgroup analyses identified IMPROVE as the superior strategy for 50–69% and 70–99% stenosis (3-year and lifetime horizon) and

Conclusions

In this modelling analysis, triage of symptomatic patients with carotid disease with the IMPROVE model can lead to the prevention of one-third of ipsilateral ischaemic strokes and perioperative strokes and deaths, while also reducing societal costs. These findings should be validated in a clinical trial.

Strategies to increase HPV vaccination among unvaccinated college students in the USA: a concept mapping study

Por: Mantina · N. M. · Palmer · K. N. B. · Yusoof · K. A. · Rajkumar · T. · Magrath · P. A. · Barraza · L. · Madhivanan · P.
Objective

The goal of this study was to identify strategies and assess priorities to increase human papillomavirus (HPV) vaccination among unvaccinated young adults using a concept mapping approach.

Design

The concept mapping process was conducted in two phases. In phase 1, eligible participants generated qualitative statements in response to a topic prompt. In phase 2, participants organised and grouped the statements by perceived similarity, and then rated each statement on a scale of perceived effectiveness. Multidimensional scaling and hierarchical cluster analysis were conducted to develop a conceptual map of the data.

Setting

This study was conducted at a university in the southwestern USA.

Participants

Eligibility criteria for participation included individuals (1) aged 18–26, (2) who had not received any dose of the HPV vaccine or were unsure if they had received the vaccine and (3) who were enrolled students at the study site institution. 24 participants engaged in the concept mapping process; five participated in phase 1 only, five participated in phase 2 only and 14 participated in both phases.

Results

The 41 statements generated were organised into five cluster concepts: media and messaging, information and education, promotion, legal and accessibility. Accessibility was the highest-rated cluster for effectiveness followed by information and education. Exploratory trends across participant demographics were also identified. Differences in perceived effectiveness of the cluster concepts were observed by gender, race, political affiliation and vaccination status.

Conclusion

This study provides valuable preliminary insights into strategies and factors perceived influential in enhancing HPV vaccination from the perspective of unvaccinated young adults. Using concept mapping, multiple factors were identified that varied in their degree of perceived effectiveness across different groups. Future HPV vaccination interventions should consider multi-component elements to ensure their success and reduce the burden of HPV-related disease.

Preparing healthcare providers to use polygenic risk scores: a qualitative study of learning needs and educational preferences

Por: Clark · A. · Wallingford · C. K. · Berkman · J. · McInerney-Leo · A. · Nisselle · A. · Terrill · B. · Palpant · N. · Young · M.-A. · James · P. A. · Yanes · T.
Objectives

Polygenic risk scores are increasingly available to consumers to provide an estimate of the genetic contribution to health conditions. However, healthcare providers report limited knowledge and confidence using polygenic risk scores. Clinical implementation necessitates educational programmes to support clinicians to integrate this new test into practice. This study aimed to identify healthcare providers’ learning needs and preferences for polygenic risk education to inform the design of tailored education initiatives.

Design, setting and participants

This pragmatic qualitative study used focus groups to capture healthcare providers’ perspectives. To ensure informed responses, genetic healthcare providers with prior experience using polygenic risk scores, and/or who had completed polygenic risk education were recruited to participate in focus groups or interviews (n=30). There were no exclusions based on country of practice. Recordings were transcribed and content analysis conducted to identify learning needs. Themes related to education engagement were mapped to the capability, opportunity and motivation model for behaviour change.

Results

Among this cohort of experienced providers, residual gaps existed in polygenic risk-related knowledge, skills and local guidelines to inform practice. Learning needs encompassed: (i) polygenic risk-specific knowledge, and (ii) communication skills needed to discuss results and facilitate risk management. Themes related to engaging with polygenic risk education mapped to capability included awareness of, and access to educational resources and initiatives, including practice resources and position statements from professional bodies. Time-poorness was a primary barrier to accessing education. Opportunities comprised of building on existing workplace training and activities such as multidisciplinary team meetings and journal clubs. All participants noted that motivation for completing polygenic risk training was primarily driven by a desire to improve patient-centred care and clinical outcomes.

Conclusion

This study highlights priority learning areas to inform the development of tailored polygenic risk education initiatives, and resources and delivery strategies that meet the identified needs. Participants’ expert insights reveal potential barriers as well as solutions to engaging healthcare providers with polygenic risk score education to ultimately facilitate implementation into clinical practice.

Mapping the evidence on anaemia across trimesters of pregnancy and risk of adverse birth outcomes in sub-Saharan Africa: a scoping review protocol

Por: Adjei-Gyamfi · S. · Zeng · I. · Aryee · P. A. · Mearns · G. J.
Introduction

Pregnancy-related anaemia significantly affects human development across life stages. In sub-Saharan Africa (SSA), country-specific epidemiological variations primarily driven by nutritional practices, socioeconomic factors and health-system disparities contribute to heterogeneity in prevalence, severity and adverse birth outcomes (ABOs). While anaemia and micronutrient deficiencies in pregnancy are well studied globally, comprehensive trimester-specific evidence and their associations with ABOs in SSA remain scarce. This review, therefore, examines the breadth and nature of existing evidence on these associations within SSA, thereby updating current knowledge and informing regionally tailored interventions and future research.

Methods and analysis

A scoping review methodology will be employed due to the limited volume of literature addressing the specific research questions and population. The review will follow the Joanna Briggs Institute (JBI) framework, applying the population-concept-context approach. Comprehensive searches will be conducted across CINAHL, MEDLINE, Cochrane Library, Scopus, Google Scholar, EBSCO Open Dissertations and relevant organisational websites. The planned search period will span from 1 January 2016 to 31 December 2025. Two reviewers will independently screen and extract data using JBI-adapted protocols within the Rayyan review platform. Any discrepancies will be resolved via discussion with the research team. Findings will be synthesised narratively through descriptive content analysis and visual mapping.

This review will include peer-reviewed studies and grey literature that investigate the associations between anaemia or deficiencies in iron, folate and vitamin B12 during pregnancy trimesters and ABOs in SSA. All relevant sources of evidence will be considered, regardless of study design or methodology, provided they report on women of reproductive age who experienced anaemia in any trimester and were subsequently identified with ABOs. Birth outcomes of interest include low birth weight, macrosomia, small or large for gestational age, preterm birth, post-term birth and stillbirth. Only sources published in English from 2016 onward will be included. The studies’ quality will be evaluated using Cochrane’s risk of bias assessment and mixed methods appraisal tools and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review.

Ethics and dissemination

This scoping review will not require ethical approval as it will synthesise published data and reports. It has been registered with the Open Science Framework. This review does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to shape subsequent research, serving as a fundamental element of the evidence and knowledge mapping framework. As this study protocol was not reviewed by an ethics committee, the appropriate contact for research integrity matters is the Faculty of Health and Environmental Sciences, Auckland University of Technology.

Early-life infectious and nutritional exposures and cardiovascular risk in early adulthood in Uganda: protocol for a new round of data collection in the Entebbe Mother and Baby Study birth cohort at 21 years (EMaBS@21)

Por: Sekitoleko · I. · Komata · R. · Ssali · I. · Kyasanku · R. · Nakyesige · R. · Sewankambo · M. · Akello · F. · Twinamasiko · N. · Namutebi · M. · Tumusiime · J. · Akantorana · C. · Akurut · H. · Balungi · P. A. · Akello · M. · Atkinson · S. H. · Niwaha · A. · Wajja · A. · Kyegombe · N. · Ny
Introduction

Non-communicable diseases, particularly cardiovascular diseases (CVDs), have become major contributors to morbidity and mortality in sub-Saharan Africa (SSA) and are projected to surpass infectious diseases as the leading cause of death among adults by 2030. Although CVDs have traditionally been associated with older age and obesity, adverse cardiovascular phenotypes are increasingly being observed in younger and leaner individuals in SSA. This pattern suggests that pathways to CVD risk in SSA may differ from those described in high-income countries. Early-life infectious exposures, undernutrition and socio-demographic conditions common in many SSA settings have been proposed as potential risk factors. Still, empirical evidence linking these exposures to cardiovascular risk in early adulthood remains limited due to a scarcity of long-running birth cohorts in the region.

Methods and analysis

This protocol describes a new round of data collection nested within the Entebbe Mother and Baby Study (EMaBS), a population-based Ugandan birth cohort established originally as a clinical trial (ISRCTN32849447) between 2003 and 2006 with prospective follow-up from pregnancy through adolescence. All participants currently under follow-up will be invited to participate at approximately 21 years of age. Primary outcomes are physiological determinants of CVD measured in early adulthood, including blood pressure, blood lipid levels, body mass index, body composition and markers of glucose metabolism. Secondary outcomes include behavioural CVD risk factors (diet, physical inactivity, alcohol use and tobacco use) and qualitative measures of CVD knowledge and risk perception. Key exposures of interest include prospectively collected early-life and childhood infectious exposures (malaria and helminth infections), markers of growth and undernutrition, micronutrient status, inflammatory markers, socio-demographic factors and selected genetic variants. Quantitative analyses will use multivariable regression and causal modelling approaches and will be complemented by qualitative interviews and focus group discussions.

Ethics and dissemination

The study protocol has been reviewed and approved by the Uganda Virus Research Institute Research and Ethics Committee (UVRI REC Ref: GC/127/35), the Uganda National Council for Science and Technology (UNCST Ref: MV625), and the London School of Hygiene & Tropical Medicine Research Ethics Committee (LSHTM Ethics Ref: 8811). Written informed consent will be obtained from all participants before study activities. Study findings will be shared and discussed with participants and community stakeholders through established engagement platforms. Results will be disseminated to the scientific community through peer-reviewed publications and conference presentations, and data will be made available to other researchers via established data-sharing platforms. We will engage policymakers at the district, national and international levels to facilitate the translation of findings into policy-relevant outputs.

Effectiveness of manual diaphragmatic techniques in adults with non-specific low back pain: a systematic review and meta-analysis protocol

Introduction

Non-specific low back pain (NSLBP) is one of the leading causes of disability worldwide. Emerging evidence suggests that altered diaphragmatic function may be associated with lumbar pain, impaired trunk stabilisation and functional disability. Manual diaphragmatic techniques have been proposed as an intervention to modulate diaphragmatic tension, mobility and neuromyofascial relationships; however, their effectiveness has not yet been synthesised using rigorous systematic review methods.

Methods and analysis

This protocol follows Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance and has been prospectively registered in PROSPERO. Randomised controlled trials evaluating manual techniques specifically applied to the diaphragm in adults with NSLBP will be eligible. The primary outcomes will include pain intensity and functional disability; secondary outcomes will include lumbar mobility, respiratory function, quality of life and adverse events. Searches will be performed in PubMed/MEDLINE, Cochrane CENTRAL, PEDro, CINAHL, Scopus, Embase and clinical trial registries without language or date restrictions. Two reviewers will independently perform study selection, data extraction and risk-of-bias (RoB) assessment using the Cochrane RoB 2 tool. Where appropriate, a random-effects meta-analysis will be conducted; the certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Substantial clinical and methodological heterogeneity is anticipated across trials, which may limit the feasibility of quantitative data pooling.

Ethics and dissemination

As this study uses data from previously published trials, ethical approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and a plain-language summary for clinical stakeholders.

PROSPERO registration

CRD420251172616.

Hybrid drug-coated balloon strategy for coronary bifurcation lesions: a systematic review and meta-analysis

Por: Dillen · D. M. M. · van Beek · K. A. J. · Vermeer · A. J. E. · Vlaar · P.-J. · El Farissi · M. · Demandt · J. P. A. · Eerdekens · R. · van het Veer · M. · Tonino · P. A. L. · Teeuwen · K.
Objectives

Recently, drug-coated balloons (DCB) have emerged as a promising alternative for side branch treatment in coronary bifurcation lesions, in combination with drug-eluting stent (DES) implantation in the main vessel, the hybrid DCB approach. We aimed to evaluate clinical outcomes in patients treated with the hybrid DCB approach and to compare this strategy with other bifurcation techniques.

Design

A systematic review and meta-analysis.

Data sources

MEDLINE and EMBASE were searched up until January 2025.

Eligibility criteria

We included randomised controlled trials and observational studies investigating clinical outcomes in patients treated with the hybrid DCB approach for coronary bifurcation lesions.

Data extraction and synthesis

Two independent reviewers extracted data and assessed the risk of bias. The outcome of interest was the combined endpoint of cardiac death, myocardial infarction (MI) or target lesion revascularisation (TLR) at the longest available follow-up. Crude event rates, stratified by treatment strategy, were provided for the overall incidence of the primary endpoint. Furthermore, we conducted meta-analyses on the combined endpoint, comparing different bifurcation percutaneous coronary intervention (PCI) strategies. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.

Results

13 studies, consisting of 2393 patients, were included in our systematic review. Investigated techniques were the hybrid DCB approach in all studies, and a two-stent strategy or the combination of DES in main vessel and balloon angioplasty (BA) in the side branch as potential comparators. Median follow-up duration was 12 months (IQR 7.5–12). The combined endpoint of cardiac death, MI or TLR was found in 5.6% in the hybrid DCB group, 15.4% in the two-stent group and in 10.0% in the BA group. The pooled analyses, including three and two studies, respectively, showed that the hybrid DCB approach was associated with a lower risk of the composite endpoint of cardiac death, MI or TLR when compared with a two-stent strategy (7.9% vs 15.4%; risk ratio (RR): 0.53; 95% CI 0.33 to 0.85) and compared with BA in the side branch (5.6% vs 10.0%; RR: 0.57; 95% CI 0.37 to 0.88). The certainty of the evidence was graded as very low.

Conclusion

The results of this systematic review and meta-analysis suggest that the hybrid DCB approach is a feasible and promising treatment approach for bifurcation lesions, when compared with other bifurcation PCI strategies. However, the results should be interpreted cautiously as the certainty of evidence was graded as very low, underlining the importance of larger trials to confirm these findings.

Trial registration number

CRD420250651469.

Beyond barriers: a qualitative evidence synthesis protocol of South Asian involvement in mental health research in high-income countries

Por: Khan · N. A. · Coventry · P. A. · Ali · H. · Fulbright · H. · Brown · J. V. E.
Introduction

There is a recognised need to provide equity in healthcare through inclusion of ethnic minorities in research. South Asians, the largest ethnic minority group in the UK, experience high levels of mental illness, often against the backdrop of socioeconomic deprivation and discrimination. The research community recognises that South Asian communities are often excluded from health research. Efforts have been made to understand the barriers and facilitators to their participation. However, the participation of individuals at the intersection of mental ill health and South Asian ethnicity remains understudied. This is a protocol for the synthesis of qualitative evidence from mental health research studies about participation, motivation and barriers to recruitment of South Asians in high-income countries.

Methods and analysis

We will search 10 databases for qualitative evidence on participation of South Asian individuals in mental health research studies in high-income countries: MEDLINE, EMBASE, PsycINFO, Health Management Information Consortium, Social Policy and Practice, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Social Sciences Citation Index, Science Citation Index Expanded and ProQuest Dissertations and Theses Citation Index. Search terms for the following five concepts will be used: (1) South Asia, (2) ethnic minority, (3) mental health conditions, (4) barriers and facilitators to participation and (5) high-income countries. No date restriction will be applied to the search. Searches will be limited to studies in the English language. Study selection and data extraction will be performed by two researchers independently, using Covidence. Demographic data, thematic outputs and salient discussion points will be extracted from final full-text inclusions and entered into NVivo for coding. Meta-ethnographic approaches using first and second-order constructs from included studies will be used to form third-order constructs. This synthesis will generate new knowledge regarding the intersectionality of mental health and South Asian ethnicity.

Ethics and dissemination

Ethical approval is not required as this study is a synthesis of published data. This review will provide new knowledge regarding the requirements for researchers and practitioners to advance the involvement of South Asian populations in mental health research. This will undoubtedly enhance equity in the long term, reduce the burden of mental disorders and enable the provision of more effective mental health care for South Asian communities.

PROSPERO registration number

CRD42025626382.

Update of the Novara Cohort Study (NCS): protocol evolution of a population-based longitudinal study on ageing in Northern Italy - cohort profile

Por: Cracas · S. V. · Garro · G. · Venetucci · J. · Martorana · M. · Antona · A. · Bettio · V. · Rossato · D. · Briacca · L. · Viola · E. · Caristia · S. · Colombo · V. · Capuzzi · L. · Roveda · C. · Varalda · M. · Rolla · R. · Sacchetti · S. · Tillio · P. A. · Capello · D. · Faggiano · F.
Purpose

The Novara Cohort Study (NCS) was established to investigate the biological, psychological and social factors that influence ageing in the general population. The study aims to identify early risk factors for frailty, allostatic load and cognitive decline, and to uncover molecular and functional markers of accelerated biological ageing. NCS addresses the need for detailed life-course data from Southern Europe to support personalised prevention and early diagnosis, and to promote healthy longevity.

Participants

NCS is a population-based, longitudinal cohort in the Novara province (Northern Italy), originally enrolling adults aged 35 and older. The inclusion criteria were later expanded to encompass all residents aged 18 and over, facilitating the study of ageing trajectories from early adulthood onward. As of mid-2025, about 1000 participants have been enrolled, and recruitment is ongoing. The cohort’s diversity in age, employment status and health conditions enhances its value for life-course analysis.

Findings to date

Following a pilot phase in 2022–2023, the whole study protocol now includes detailed demographic, clinical, behavioural, cognitive and psychosocial data, along with biological samples stored in the UPO Biobank. The protocol incorporates validated tools, comprehensive physical and cognitive assessments, and over 90 laboratory biomarkers covering inflammation, metabolism, hormonal function and coagulation. Additionally, a subset of participants underwent advanced inflammatory profiling by simultaneous measurement of 92 immune-related proteins and comprehensive genomic profiling using Illumina Single Nucleotide Polymorphism (SNP) arrays, capturing common genetic variation across multiple biological domains. Preliminary results demonstrate the feasibility of integrating deep phenotyping, reveal the roles of frailty in ageing and show initial evidence of age-related changes in inflammatory proteins.

Future plans

NCS plans to enrol at least 10 000 participants and will conduct long-term follow-up using both passive methods, such as linking with clinical records and administrative health databases, and active in-person reassessments. Future phases will integrate clinical, behavioural and cognitive data with large-scale omics analyses, including genomics, proteomics, metabolomics and transcriptomics. Machine learning techniques will be employed to model biological age, identify early signs of age-related decline and develop personalised prevention strategies. By combining high-resolution phenotyping with multidimensional data, NCS aims to find modifiable risk factors and molecular signatures of ageing, supporting national and European research efforts and encouraging collaborative studies through open data-sharing frameworks.

Exploring barriers to integrated care for children under 5 living in temporary accommodation: a qualitative study of professionals experiences during the COVID-19 pandemic in England

Por: Pierce · P. A. S. · Svirydzenka · N. · Adil · H. · Allaham · S. · Ankers · M. · Parry · Y. K. · Heys · M. · Ucci · M. · Lakhanpaul · M.
Objectives

This research aims to explore the factors that hinder professionals in delivering integrated care for children under 5 in temporary accommodation (TA) and understand their experiences of collaboration during the pandemic to inform recommendations.

Design

Semistructured qualitative interviews.

Setting

England, UK.

Participants

45 professionals working across health, housing, education and non-profit sectors in England. Purposive and snowball sampling was employed to recruit a representation of key professionals across England. Those not eligible to take part in the study included people who did not work with families and/or children in TA settings.

Outcome measures

To explore cross-sector learnings that are applicable to improving integrated care and to tailor recommendations to the needs of families and children under 5 experiencing homelessness in the UK today.

Results

This study highlights the complex, multilevel barriers that professionals face when delivering integrated care to children under 5 in TA. Findings are organised using a framework that distinguishes between practice-level, organisational and systemic challenges. From siloed working practices and limited training to staffing shortages and restrictive data-sharing policies, these challenges collectively hinder service continuity and collaboration.

Conclusions

Although this project was conducted during the COVID-19 pandemic, the challenges identified reflect deeper, long-standing issues in service delivery. As services continue to recover and prepare for future crises, these insights remain highly relevant and can inform more resilient, integrated recovery plans to support children in TA beyond the pandemic context. Addressing these barriers, through improved collaboration, training and data-sharing, is key to strengthening care for this vulnerable population.

Study protocols for the GEPard project: systematic analysis of sex- and gender-specific differences in the efficacy of perioperative pain management - a two-pronged approach

Por: Floren · S. · Segelcke · D. · Machacek · P. A. · Vollert · J. · Norda · H. · Rohde · I. · Gilron · I. · Pogatzki-Zahn · E. M.
Introduction

Postoperative pain is common, with approximately one-third of surgical patients experiencing severe acute pain and 10–20% developing chronic post-surgical pain (CPSP). Evidence shows that female patients are at higher risk of pain after sex non-specific surgery, thus sex- or gender-specific differences in pain treatment efficacy with potential consequences for perioperative pain management are to be expected. Considering the clinical and societal burden of poorly managed postoperative pain, the GEPard project comprises two systematic reviews, GEPard 1: sex- and/or gender-specific differences in efficacy of perioperative pain management for certain (major) surgical procedures in adult patients; and GEPard 2: sex- and/or gender-specific differences in the dosing, efficacy and adverse effects of the most common systemic perioperative non-opioid- and co-analgesics across all sex non-specific surgical procedures in adult patients.

Methods and analysis

The reviews will be conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook. MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov and PsycINFO will be searched. We will include randomised controlled trials (RCTs) and systematic reviews/meta-analyses reporting outcomes disaggregated by sex and/or gender in adult surgical patients. For GEPard 1, this applies to selected major surgical procedures; for GEPard 2, to all non-sex-specific surgical procedures. Interventions include regional anaesthesia, systemic analgesics and psychological strategies for GEPard 1 and non-opioid- as well as co-analgesics for GEPard 2. Two reviewers will independently screen and extract the data. Cochrane Risk of Bias Tool 2.0 (RoB 2) and AMSTAR 2 tools will assess study quality. Random-effects or Bayesian meta-analyses will be performed where possible; otherwise, narrative synthesis will be applied. GRADE methodology will assess evidence certainty.

Ethics and dissemination

No ethical approval is required for these reviews. Findings will be disseminated via peer-reviewed publications, patient organisations and professional societies. Data will be shared via Zenodo or Open Science Framework (OSF), following FAIR principles.

PROSPERO registration number

The systematic review protocols for both reviews have been registered in PROSPERO on 29 August 2025 (Registration-ID: CRD420251121393 (GEPard1), CRD420251121536 (GEPard2).

Global scoping review of key domains of patient-reported experience of care measures across life stages and healthcare technical areas

Objectives

Patient-reported experience measures (PREMs) are measures of patients’ perceptions of care they receive. PREMs are critical in developing and evaluating programmes that aim to improve patient healthcare experiences and quality of care (QoC) according to patient-defined needs. This review aims to map key domains of PREMs across distinct healthcare technical areas and life stages from globally available literature.

Design

A scoping review adapting Arksey and O’Malley’s framework and Joanna Briggs Institute’s guidelines for the conduct of scoping reviews.

Data sources

Google Scholar, PubMed, WHO, US Academy of Medicine and USAID Momentum.

Eligibility

PREMs literature from electronic repositories of grey and peer-reviewed publications, published in English historically up to September 2023.

Data extraction and analysis

Two lead reviewers with support from the technical working group co-created a review framework of healthcare technical areas, life stages and PREMs domains. We screened eligible articles, prioritising reviews except for technical areas with no reviews, where we then selected individual studies. We charted, analysed and synthesised data from 52 eligible articles.

Results

PREMs literature has recently increased, especially in low-income and middle-income countries (LMICs), although studies in high-income countries (HICs) dominate in proportion (n=38; 73.1%). Out of 52 eligible articles, technical areas with most publications were sexual and reproductive health (n=21; 40.4%) and general outpatient care (n=11; 21.2%). Studies in adulthood (n=24; 46.2%) and from pregnancy and birth to postnatal (n=16; 30.8%) were most represented. PREMs studies reported mostly on communication and rapport (n=33; 63.5%) and respect and dignity (n=42; 80.8%) domains. Nearly a quarter (n=12; 23.1%) of the articles included only validated tools; the rest included a combination of validated and unvalidated measures. Of the tools relating to life stages of babies, younger children and older adults, the majority (n=17; 94.4%) included patient proxies.

Conclusion

PREMs, as an important component of QoC measurement, are increasing across several healthcare technical areas and life stages with commonalities and notable distinctions in measurement domains and tools. Evidence on PREMs largely comes from HICs. Evidence on critical, yet sometimes overlooked domains, highlights key QoC implementation gaps. The adaptation and utilisation of PREMs in programmes, especially in LMICs and under-represented technical areas, present opportunities to close the QoC disparities in those settings. Strategic, concerted efforts towards the harmonisation of PREMs tools across multiple life course stages and technical areas are critically needed in high-level quality improvement efforts.

A Neonatal Nurse‐Controlled Model of Analgesia to Manage Post‐Operative Pain in the Surgical Neonate: A Pilot Randomised Controlled Trial

ABSTRACT

Aim

To test the feasibility and acceptability of a newly developed model of neonatal nurse-controlled analgesia to manage pain in the post-operative infant.

Design

The study utilised a single-centre two-arm parallel, unblinded randomised controlled external pilot trial design.

Methods

The pilot trial was conducted in a surgical neonatal tertiary intensive care unit in Brisbane, Australia. Eligible infants were randomised to receive either post-operative pain management care via a model of neonatal nurse-controlled analgesia or standard care. Feasibility and acceptability were the primary outcomes. Seven feasibility outcomes were assessed by a traffic light system to delineate progression to a larger trial. Acceptability and clinical utility of the model of care by staff were assessed by feedback from an anonymous questionnaire that was administered at the completion of the trial period. Secondary outcomes included parental attitudes and perceptions of post-operative pain management to help establish primary outcomes for a larger randomised controlled trial.

Results

Overall staff found the formalised model beneficial for managing post-operative pain but found the complexity of the model and ability to titrate analgesia based only on documented pain scores barriers requiring further consideration. Three of the seven feasibility outcomes failed to reach ‘greenlight’ targets to progress to a larger trial with adherence to the model, and the proportion of eligible infants not recruited was allocated a ‘redlight’. Secondary outcomes were comparable and support future study.

Conclusion

This pilot feasibility study has shown that a model of neonatal nurse-controlled analgesia can be safely implemented and utilised in the post-operative care of the surgical neonate. Further exploration of the barriers to model adherence and recruitment is warranted before a future larger trial is undertaken.

Impact

Though not all primary outcomes reached an acceptable range for further progression, this pilot feasibility study provided invaluable learning and has provided direction for future research into the provision of a family integrated and responsive model of analgesia.

Reporting Method

This study is reported in line with the Consolidated Standards of Reporting Trials (CONSORT): Extension to randomised pilot and feasibility trial and the TIDieR Checklist (Template for Intervention, Description and Replication).

Public or Patient Contribution

No patient or public contribution was utilised for this study.

Trial Registration: ACTRN12623000643673—the trial was prospectively registered

Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study

Por: Myint · A. P. · Shirreff · G. · Baillie · V. · Bal · A. · Boutros · C. F. · Burtseva · E. · Coulibaly · D. · Danilenko · D. · Dbaibo · G. · Destras · G. · Dia · N. · Draganescu · A. C. · Giamberardino · H. I. G. · Komissarov · A. B. · Koul · P. A. · Laguna-Torres · V. A. · LeBlanc · J.
Objective

The objective of this study was to determine the association between viral subtype/clade and disease severity.

Design

Multicentre retrospective cohort study.

Setting

This study used data from the Global Influenza Hospital Surveillance Network (GIHSN). The dataset comprised hospitalised influenza patients with viral sequencing data across 14 countries, collected from August 2022 through October 2023.

Participants

A total of 761 hospitalised patients were enrolled during the study period, and 745 patients were included in the analysis. We excluded patients with missing data on explanatory or outcome variables, those infected with viral clades represented by fewer than 11 sequences, and those enrolled at study sites contributing fewer than 5 patients.

Outcome measures

Disease severity was defined by admission to intensive care unit (ICU), receipt of non-invasive oxygen supplementation, 3-variable definition (ICU, mechanical ventilation or death) or 4-variable definition (3-variable plus oxygen supplementation).

Outcomes were analysed in association with subtype or clade using the mixed-effects logistic regression models, adjusting for age group, sex, underlying medical conditions, influenza vaccination status, antiviral use, country income level and epidemic period, while study site was included as a random effect.

Results

745 patients were included: 263 A(H1N1)pdm09, 380 A(H3N2), 102 B/Victoria. A(H1N1)pdm09 infection was associated with increased odds of ICU admission (adjusted ORs (aORs) 2.5, 95% CI 1.1 to 5.8) compared with A(H3N2). 6B.1A.5a.2a.1 clade of A(H1N1)pdm09 was associated with increased severity compared with 6B.1A.5a.2a clade (aOR 3.0, 95% CI 1.0 to 9.5) and (aOR 5.4, 95% CI 1.6 to 18.3) for the 3-variable and 4-variable definitions respectively. Among A(H3N2), the (3C.2a1b.2a.)2b clade showed a trend toward increased severity using the 4-variable definition compared with the 2a.1b clade (aOR 2.9, 95% CI 0.8 to 10.0).

Conclusions

This analysis highlights the differential impact of influenza subtypes and clades on disease severity in hospitalised patients. Future research should investigate the role of specific viral mutations of these clades in modulating immune evasion or disease severity. These findings reinforce the GIHSN’s critical role in global surveillance. Ongoing genomic surveillance is crucial for understanding the clinical impact of emerging influenza variants and informing public health responses.

Prophylaxis for venous thromboembolism in traumatic brain injury: protocol for a randomised controlled trial

Por: Pirouzmand · F. · Mathieu · F. · Mansouri · A. · Kavikondala · K. · Alkins · R. · Boyd · J. G. · Christie · S. · Couillard · P. · Cusimano · M. D. · Engels · P. T. · English · S. · Fourney · D. · Fowler · R. · Geerts · W. · Gooderham · P. A. · Griesdale · D. · Hunter · G. · Jabehdar Mara
Introduction

Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

Methods and analysis

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

Ethics and dissemination

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

Trial registration number

NCT03559114.

Palliative care consultation for end-of-life decision-making in hospitalised patients: protocol for a systematic review and meta-analysis

Por: Haddad · G. · Ajzenberg · H. · Davis · F. D. · Fogelman · P. A. · Korzick · K. · Marshall · M. F. · Naylor · D. · Swoboda · S. M. · Reid · J. · Oczkowski · S.
Introduction

Hospitalised patients nearing the end of life (EOL) often face complex treatment decisions, leading to potential conflicts among care teams, patients and families. Palliative care consultations may enhance decision-making processes, improve satisfaction and reduce unnecessary interventions. This systematic review will assess the impact of palliative care consultations on treatment decisions, family and patient satisfaction, and psychological outcomes in hospitalised adults.

Methods and analysis

We will include randomised controlled trials comparing palliative care consultations to standard care in hospitalised adults. The primary outcomes will include decisions to withhold or withdraw treatments, patient and family satisfaction with EOL decision-making, and psychological outcomes such as anxiety, depression and post-traumatic stress disorder. Secondary outcomes will include intensive care unit (ICU) and hospital length of stay, utilisation of potentially non-beneficial treatments, and the use of institutional policies or legal actions. Databases including MEDLINE, Embase, CINAHL, Cochrane CENTRAL and PsycINFO will be systematically searched from inception to September 2025. Two independent reviewers will screen studies and extract data using Covidence. Meta-analyses will use random-effects models to generate pooled estimates for primary and secondary outcomes. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool, and evidence certainty will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Subgroup analyses will explore variations by ICU versus non-ICU settings, cancer versus non-cancer diagnoses and default versus clinician-initiated consultations.

Ethics and dissemination

Ethical approval is not required for this review. Findings will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD420250624190.

Public-private mix for tuberculosis in urban health systems in least-developed, low-income and lower-middle-income countries and territories: a systematic review

Por: Vidyasagaran · A. L. · Teixeira de Siqueira Filha · N. · Kakchapati · S. · Hall · T. F. · Naznin · B. · Tajree · J. · Quayyum · Z. · Joshi · D. · Sibeudu · F. T. · Ogbozor · P. A. · Arize · I. N. · Shrestha · G. · Golder · S. · Ahsan · M. · Adhikary · S. · Agwu · P. · Elsey · H.
Objective

To evaluate the impact of public–private mix (PPM) models for tuberculosis (TB) on health, process and system outcomes, adopting the WHO’s definition of PPM, which is a strategic partnership between national TB programmes and healthcare providers, both public and private, to deliver high-quality TB diagnosis and treatment.

Design

Systematic review without meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Data sources

EMBASE, MEDLINE, Health Management Information Consortium, Social Sciences Citation Index, Science Citation Index, Emerging Sources Citation Index, CENTRAL, Database of Disability and Inclusion Information Resources, WHO Library Database and 3ie.

Eligibility criteria

We included all primary studies examining PPM models delivering TB services in urban health sectors in least-developed, low-income and lower–middle-income countries and territories.

Data extraction and synthesis

17 reviewers were involved in data extraction in COVIDENCE using a prepiloted template. All extractions were completed by a single reviewer and checked by a second reviewer. Quality appraisal was carried out using the mixed-methods appraisal tool, covering mixed-methods, qualitative and quantitative study designs. Narrative synthesis was carried out by tabulating and summarising studies according to PPM models and reported in line with the synthesis without meta-analysis guidelines.

Results

Of the 57 included studies, covering quantitative (n=41), qualitative (n=6) and mixed-method (n=10) designs, the majority were from Southeast Asia (n=37). PPM models had overall positive results on TB treatment outcomes, access and coverage and value for money. They are linked with improved TB health workers’ skills and service delivery. Most outcomes tended to favour interface models, although with considerable heterogeneity. Inconsistent implementation of national TB guidelines, uncoordinated referrals and lack of trust among partners were identified as areas of improvement. Evidence was lacking on the involvement of informal providers within PPM models.

Conclusions

PPM models can be effective and cost-effective for TB care in urban low- and middle-income countries contexts, particularly when levels of mistrust between public and private sectors are addressed through principles of equal partnership. The evidence indicates that this may be more achievable when an interface organisation manages the partnership.

PROSPERO registration number

CRD42021289509.

Incidence of all-cause mortality in prisons: research protocol for a global registry study and systematic literature review with meta-regression analyses

Por: Mundt · A. P. · Rozas-Serri · E. · Asencio Rojas · B. I. · Morales-Rojas · A. · Cifuentes-Gramajo · P. A. · Alvarado · S. · Baranyi · G. · Borschmann · R. · Fazel · S. · Kinner · S. A.
Introduction

People in prison experience disproportionate health burdens compared with community-based populations, including elevated rates of infectious and non-communicable diseases, mental illness and substance use disorders. Previous studies have consistently shown increased rates of mortality following release from incarceration, particularly from external (unnatural) causes such as suicide and violence. However, evidence on mortality incidence during imprisonment is scarce, and many deaths may be preventable through targeted health and prevention interventions. This study aims to synthesise worldwide evidence on all-cause mortality incidence in prisons.

Methods and analysis

We will conduct a worldwide registry study combined with a systematic literature review and meta-regression analysis. Eligible sources will report deaths among incarcerated people between 2005 and 2025 at the national or, where more appropriate, the subnational jurisdictional level. Mortality data will be retrieved from official reports of prison administrations and direct contact with prison authorities. Also, data from international databases and the scientific literature will be reviewed. Incidence rates of all-cause mortality per 100 000 person-years will be calculated and reported for each jurisdiction, alongside standardised mortality ratios comparing imprisoned populations with general population estimates.

Ethics and dissemination

Since the study relies on anonymised routine data registries available from different sources, an exemption certificate was granted by the Ethics Committee of Diego Portales University (UDP) in Santiago, Chile. Findings will be submitted for publication in a peer-reviewed academic journal.

Trial registration number

https://osf.io/vkzae.

At the epicentre: a qualitative study of how parents of a child with de novo retinoblastoma experience the diagnostic process and primary treatment

Por: Lou · S. · Carstensen · K. · Mikkelsen · P. A. · Jensen · P. S. · Hogild · M. L. · Christensen · R. T. · Overgaard · J. · Urbak · S. F. · Staffieri · S. E. · Gregersen · P. A.
Objective

To explore how parents of children with de novo retinoblastoma (RB) experience the diagnostic process and acute treatment phase, and to identify factors that may support parental coping and adaptation.

Design

A qualitative interview study using reflexive thematic analysis.

Setting

National Retinoblastoma Unit at Aarhus University Hospital, Denmark.

Participants

Thirty-one parents (21 mothers, 10 fathers) of 21 children diagnosed with de novo RB were recruited via hospital follow-up clinics and a support group day.

Results

For most parents, the diagnostic process was short. In cases of diagnostic delay, parents described frustration and guilt due to missed symptoms. Receiving the RB diagnosis was described as a surreal experience, accompanied by feelings of shock, grief and loss of control. Parents faced challenges in adapting to rapid medical decisions and the unfamiliar demands of hospital protocols. However, meeting the clinical experts was a relief, as parents felt they were in capable hands, experiencing empathetic communication and a clearly framed treatment plan. Parents emphasised the importance of support systems, including family, healthcare professionals and the child’s resilience, as crucial for coping with and managing the diagnosis.

Conclusions

Parents faced a sudden and disruptive transition from symptom recognition to life-altering diagnosis and treatment. While professional care and communication were experienced as supportive, they did not eliminate the emotional impact. Clinical pathways should prioritise early validation of parental concerns and provide transparent communication, both prior to referral and throughout treatment. Future research should examine longer-term parental adjustment and identify interventions that support emotional resilience beyond the acute phase.

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