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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

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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.

PharmacoGENEtics in Youth Depression (GENE-YD) Study protocol: a pilot triple-blinded randomised controlled trial using pharmacogenetics to tailor antidepressant treatment in young Australians

Por: Roberts · B. · Cooper · Z. · Miljevic · A. · Stanley · S. H. · Majda · B. T. · Collins · K. R. L. · Baltic · S. · Lindsey-Temple · S. E. · Akkari · P. A. · Hood · S. D. · Rodger · J.
Background

The prevalence of depression and mood disorders has been steadily rising in Australian youth, with a concomitant increase in antidepressant pharmacotherapy prescription rates. Yet, the tolerability and efficacy of antidepressant drugs in youth remain poor. Pharmacogenetic (PGx) testing, or the personalised and guided treatment of medication based on genetic data, has been suggested to improve the effectiveness and tolerability of antidepressants. However, limited studies have evaluated the utility of antidepressant PGx-guided treatment in adolescent and young adult populations. Thus, this pilot randomised controlled trial (RCT), the GENE-YD Study, will evaluate the feasibility for a large-scale RCT assessing the effect of PGx-guided antidepressant prescription vs treatment as usual in youth with major depressive disorder (MDD).

Methods and analysis

Eighty young people between 16 and 24 years of age and in the early stages of pharmacotherapy treatment for MDD will be recruited. Following initial screening, participants will be randomised on a 1:1 ratio to either the intervention or control study group. Participants in the intervention condition will have their treatment tailored based on their PGx profile. Participants randomised into the control group will have their prescription based on current best practice recommendations, or treatment as usual. Individuals will be assessed at drug prescription baseline and again 6 and 12 weeks following drug prescription. The primary outcome of the study will be to evaluate the feasibility and acceptability of the GENE-YD protocol. Specifically, this study will explore participation recruitment strategies and attrition to the study protocols to guide the recruitment processes of a large-scale RCT, along with participating satisfaction in overall study protocols. Secondary outcomes will inform the utility and variability of specific measures (eg, depression rating scales, quality of life measures and medication adherence scales) that may be scaled up for use in a future full-scale trial.

Ethics and dissemination

Ethics approval was granted by the Department of Health, Western Australia’s Human Research Ethics Committee (RGS0000006822) and recognised by the University of Western Australia’s Human Research Ethics Committee (2024/ET000685). All participants will be required to provide written informed consent. Results will be published in international peer-reviewed journals.

Trial registration number

ACTRN12624000760572.

Prioritizing food systems interventions to reduce adolescents nutrition insecurity and malnutrition in low-income settings: protocol for the Dishi Fiti Ishi Fiti (Eat Well Live Well) mixed-methods study

Por: Lee · G. O. · McCormick · B. J. · Staromiejska · W. · Mutuku · V. · Fox · E. L. · Kimenju · S. · Mawa · P. A. · Asiki · G. · Downs · S.
Introduction

Adolescents in informal urban communities, defined as settlements that fall outside of formal governmental planning and regulatory frameworks, are at increasing risk of poor-quality diets and malnutrition in all its forms. The food environment is the interface of adolescent food choice and the broader food system, and food environment interventions have the potential to improve adolescent diets and nutritional outcomes.

Methods and analysis

We will conduct a mixed-methods study, integrating methods from participatory systems science and nutritional epidemiology to characterise linkages among adolescents’ neighbourhood and home food environments, and their food choices, diets and nutritional outcomes. We will recruit adolescents, caregivers, school staff and food system actors from five communities along a gradient of urban informality in Nairobi, Kenya, to participate in cognitive mapping, group-based modelling and a cohort study over one academic year to evaluate dietary choices and nutritional outcomes.

Ethics and dissemination

The study has been approved by the Research Ethics Committee of Rutgers University (Pro2024001981) and Amref Health Africa (P1831-2025). Adult participants will provide written informed consent, and adolescents will provide written informed assent to participate in the study. Findings will be disseminated through peer-reviewed journals, conference presentations and to participants through planned participatory interaction throughout the study.

Investigating the capability of deep learning models to predict age and biological sex from anterior segment ophthalmic imaging: a multi-centre retrospective study

Por: Balal · S. · Cox · L. · Khan · A. · Kandakji · L. · Leucci · M. · Keane · P. A. · Gore · D. · Pontikos · N. · Allan · B.
Objective

To assess the capability of a convolutional neural network trained by transfer learning on anterior segment optical coherence tomography (AS-OCT) images, Placido-disk corneal topography images and external photographs to predict age and biological sex.

Design

Development of a deep learning model trained on retrospectively collected data using transfer learning.

Setting

A multicentre secondary care public health trust based in London.

Participants

We included 557,468 scans from 40,592 eyes of 20,542 patients. Data were extracted from all patients who underwent MS-39 imaging within our trust from October 2020 to March 2023.

Primary and secondary outcome measures

Primary outcome measures for biological sex classification included accuracy, precision, recall, F1-score and area under the receiver operating curve (ROC-AUC). Primary outcome measures for age prediction were Pearson correlation coefficients (r), coefficients of determination (R²) and the mean absolute error (MAE) to evaluate the predictive performance. The secondary outcome was to visualise and interpret the model’s decision-making process through the construction of saliency maps.

Results

For age prediction, the MAEs for the Placido, AS-OCT and external photograph models were 5.2, 5.1 and 6.2 years, respectively. For gender classification, the same models achieved ROC-AUCs of 0.88, 0.73 and 0.81, respectively. No difference in performance was found in the analysis of corneas with pathological topography. The saliency maps highlighted the peri-limbal cornea for age prediction and the central cornea for gender discrimination.

Conclusions

Our study demonstrates that deep learning models can extract age and gender information from anterior segment images. These findings support the concept that the anterior segment, like the retina, encodes important biological information. Future research should explore whether these models can predict specific systemic conditions.

Impact of CMV-specific immune reconstitution at the end of letermovir prophylaxis on the development of late cytomegalovirus infection in haematopoietic stem cell transplant recipients (INMUNOEND): a protocol for a prospective, observational, multicentre

Por: Caston · J. J. · Aparicio · C. · Paez-Vega · A. · Pozo Lopez · L. · Garcia · E. · Martin · C. · Ruiz-Arabi · E. · Cuesta-Casas · M. A. · Bermudez-Rodriguez · M. A. · Cerezo-Martin · J. M. · Gonzalez-Sierra · P. A. · Machuca · I. · Martin Dominguez · F. M. · Saldana-Moreno · R. · He
Introduction

Cytomegalovirus (CMV) infection is a common complication in patients undergoing haematopoietic stem cell transplantation (SCT). Letermovir (LTV) prophylaxis during the first 100 days post-SCT is effective and safe in preventing this infection, although it may be associated with a delay in CMV-specific immune reconstitution. Hence, a study is needed to evaluate whether the absence of CMV-specific immune reconstitution at the end of LTV prophylaxis is associated with the development of late infection. This could facilitate the individualisation of CMV prophylaxis duration in these patients.

Methods and analysis

INMUNOEND is a multicentre, prospective, observational, non-interventional study including CMV seropositive patients undergoing allo-SCT who receive LTV prophylaxis during the first 100 days post SCT. Immunological and virological monitoring will be conducted until day+200 post-SCT. The primary outcome is the percentage of patients who develop clinically significant CMV infection up to day+200 post-SCT after completing LTV prophylaxis. Data collected will include baseline characteristics of the haematological diseases and comorbidities, variables related to SCT (ie, engrafment, graft-versus-host disease, use of LTV and CMV replication) and variables related to CMV-specific immune reconstitution.

Ethics and dissemination

Ethical approval has been obtained from the institutional review board (Comité de Ética de la Investigación de Córdoba; SICEIA-2024–0 01 762). The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences.

Trial registration number

NCT06814301.

Effectiveness of vaccination in patients undergoing dialysis or patients with chronic kidney disease: a systematic review protocol

Por: Karim · M. · Milone · B. · Buh · A. · Wisener · N. · Benomar · C. · Mei Nsen · P. · Akbari · A. · Brown · P. A. · Hundemer · G. L. · Sood · M.
Introduction

Vaccination has been an effective public health intervention for immunising individuals against many common communicable and non-communicable diseases. However, there is limited information on the efficacy of vaccination among patients undergoing dialysis or patients with chronic kidney disease (CKD). The objective of this review is to assess the effectiveness of vaccination within dialysis and CKD patient populations.

Methods and analysis

This will be a systematic review of studies assessing the effectiveness of vaccination among CKD and dialysis patients. Relevant studies will be identified using MEDLINE, Embase, Scopus and Cochrane Library. All searches will be conducted from database inception to October 2025. Only observational studies such as cohort, prospective, retrospective and cross-sectional studies will be included. Data pertaining to patient outcomes and study design will be extracted. A narrative synthesis will be conducted as well as a meta-analysis if data permitting this analysis is extracted from included studies.

Ethics and dissemination

Since data collection will be conducted by examining existing studies, no ethical approval or consent will be required. The results of this review will be published in a peer-reviewed journal as well as presented at seminars, conferences and symposiums.

Trial registration number

This review protocol has been registered in International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42025648534.

Understanding structured medication reviews delivered by clinical pharmacists in primary care in England: a national cross-sectional survey

Por: Agwunobi · A. J. · Seeley · A. E. · Tucker · K. L. · Bateman · P. A. · Clark · C. E. · Clegg · A. · Ford · G. · Gadhia · S. · Hobbs · F. D. R. · Khunti · K. · Lip · G. Y. H. · de Lusignan · S. · Mant · J. · McCahon · D. · Payne · R. A. · Perera · R. · Seidu · S. · Sheppard · J. P. · Willia
Objectives

This study explored how Structured Medication Reviews (SMRs) are being undertaken and the challenges to their successful implementation and sustainability.

Design

A cross-sectional mixed methods online survey.

Setting

Primary care in England.

Participants

120 clinical pharmacists with experience in conducting SMRs in primary care.

Results

Survey responses were received from clinical pharmacists working in 15 different regions. The majority were independent prescribers (62%, n=74), and most were employed by Primary Care Networks (65%, n=78), delivering SMRs for one or more general practices. 61% (n=73) had completed, or were currently enrolled in, the approved training pathway. Patient selection was largely driven by the primary care contract specification: care home residents, patients with polypharmacy, patients on medicines commonly associated with medication errors, patients with severe frailty and/or patients using potentially addictive pain management medication. Only 26% (n=36) of respondents reported providing patients with information in advance. The majority of SMRs were undertaken remotely by telephone and were 21–30 min in length. Much variation was reported in approaches to conducting SMRs, with SMRs in care homes being deemed the most challenging due to additional complexities involved. Challenges included not having sufficient time to prepare adequately, address complex polypharmacy and complete follow-up work generated by SMRs, issues relating to organisational support, competing national priorities and lack of ‘buy-in’ from some patients and General Practitioners.

Conclusions

These results offer insights into the role being played by the clinical pharmacy workforce in a new country-wide initiative to improve the quality and safety of care for patients taking multiple medicines. Better patient preparation and trust, alongside continuing professional development, more support and oversight for clinical pharmacists conducting SMRs, could lead to more efficient medication reviews. However, a formal evaluation of the potential of SMRs to optimise safe medicines use for patients in England is now warranted.

Quantitative retinal morphology and mortality in individuals with proliferative diabetic retinopathy: a retrospective cohort study in a large real-world population

Por: Khan · A. Z. · Ribeiro Reis · A. P. · Olvera-Barrios · A. · Zhou · Y. · Williamson · D. J. · Struyyen · R. R. · Khalid · H. · Egan · C. · Denniston · A. K. · Keane · P. A. · Wagner · S. K.
Objectives

To investigate whether quantitative retinal markers, derived from multimodal retinal imaging, are associated with increased risk of mortality among individuals with proliferative diabetic retinopathy (PDR), the most severe form of diabetic retinopathy.

Design

Longitudinal retrospective cohort analysis.

Setting

This study was nested within the AlzEye cohort, which links longitudinal multimodal retinal imaging data routinely collected from a large tertiary ophthalmic institution in London, UK, with nationally held hospital admissions data across England.

Participants

A total of 675 individuals (1129 eyes) with PDR were included from the AlzEye cohort. Participants were aged ≥40 years (mean age 57.3 years, SD 10.3), and 410 (60.7%) were male.

Outcome measures

The primary outcome was all-cause mortality. Quantitative retinal markers were derived from fundus photographs and optical coherence tomography using AutoMorph and Topcon Advanced Boundary Segmentation, respectively. We used unadjusted and adjusted Cox-proportional hazards models to estimate hazard ratios (HR) for the association between retinal features and time to death.

Results

After adjusting for sociodemographic factors, each 1-SD decrease in arterial fractal dimension (HR: 1.54, 95% CI: 1.18 to 2.04), arterial vessel density (HR: 1.59, 95% CI: 1.15 to 2.17), arterial average width (HR: 1.35, 95% CI: 1.02 to 1.79), central retinal arteriolar equivalent (HR: 1.39, 95% CI: 1.05 to 1.82) and ganglion cell-inner plexiform layer (GC-IPL) thickness (HR: 1.61, 95% CI: 1.03 to 2.50) was associated with increased mortality risk. When also adjusting for hypertension, arterial fractal dimension (HR: 1.45, 95% CI: 1.08 to 1.92), arterial vessel density (HR: 1.47, 95% CI: 1.05 to 2.08) and GC-IPL thickness (HR: 1.56, 95% CI: 1.03 to 2.38) remained significantly associated with mortality.

Conclusions

Several quantitative retinal markers, relating to both microvascular morphology and retinal neural thickness, are associated with increased mortality among individuals with PDR. The role of retinal imaging in identifying those individuals with PDR most at risk of imminent life-threatening sequelae warrants further investigation.

Rationale and methodology of a multicentric prospective cohort study on 'Longitudinal Effects of Air Pollution Exposure on Adolescent Lungs (APEAL) in urban India: APEAL protocol

Por: Agrawal · T. · Phuleria · H. C. · Mohan · A. · DSouza · G. · Thimmulappa · R. · Jayaraj · B. S. · Mani · M. R. · Patil · S. · Samdarshi · P. · Nori-Sarma · A. · Wellenius · G. · Mahesh · P. A.
Introduction

Air pollution is a significant global health concern, with studies from the USA and Europe linking long-term exposure to respiratory issues and poor school attendance in children. While Indian cities experience much higher pollution levels, the impact on lung development in Indian children remains unclear. This study aims to assess the burden of impaired lung function in Indian children and identify key factors contributing to pollution-induced lung injury.

Methods and analysis

This longitudinal, prospective cohort study is conducted in four cities categorised by particulate matter 2.5 (PM2.5) levels: ‘very high’ (Delhi), ‘high’ (Mumbai, Bangalore) and ‘moderate’ (Mysore). A total of 4000 participants (1000 from each city) will be included in the study. Participants will complete a structured questionnaire covering sociodemographics, asthma and allergy history (International Study of Asthma and Allergies in Childhood core questionnaire), dietary intake (24-hour recall and Food Frequency Questionnaire), Physical Activity-C Questionnaire and air pollution exposure. Spirometry and Forced Oscillation Technique will be used to assess lung function. Blood samples will be collected for identification of biomarkers to predict lung impairment. After quality checks, data will be compiled, summarising pulmonary function parameters alongside covariates and confounders. Analysis of Variance (ANOVA) will assess between-city and within-city differences in lung function.

We anticipate a higher prevalence of reduced lung function in children residing in cities with very high and high PM2.5 levels compared with the moderately polluted city. Findings from this study could establish normal age-appropriate lung function reference values for Indian urban children, aiding in clinical diagnosis.If a reliable biomarker for identifying children at risk of lung impairment is available, it could serve as an early predictor of poor lung health in asymptomatic children.

Ethics and dissemination

The approval from individual site institutional review board (IRB) is obtained prior to initiation of the study from institutional ethics committee, St. John’s Medical College and Hospital, Bangalore; institutional ethics committee, JSS Medical College, Mysore; institute ethics committee, Indian Institute of Technology Bombay and institute ethics committee, All India Institute of Medical Sciences. Findings from this study will be disseminated through conference presentations, peer-reviewed publications and establishment of normal age-appropriate lung function reference values for children living in urban India.

Sex differences in onset and prevalence of 108 diseases and multimorbidity across lifespan in Yichang, China: quantitative analysis of real-world linked electronic health records

Por: Wang · Y. · Yang · J. · Tong · X. · Hu · C. · Zhang · J. · Long · Y. · Yang · Y. · Lu · Z. · Shao · W. · Wang · Y. · Xu · H. · Xu · X. · Ng · S.-K. · Scuffham · P. A. · Zhou · M. · Feng · L. · Gong · E. · Shao · R. · Wang · C.
Objective

The magnitude and persistence of diseases and multimorbidity between females and males are different. This study comprehensively quantified sex differences in the onset and progression of 108 major physical and mental diseases to multimorbidity through adulthood in Chinese population.

Design

Quantitative analysis of real-world linked electronic health records.

Setting

Linked health records from 160 health facilities across primary, secondary and tertiary healthcare, comprising routinely collected electronic health records from the whole urban residents of Yichang, China between 1 January 2016 and 31 December 2019.

Participants

684 455 urban residents aged 20 years and above with documented health records during the study period.

Main outcomes measures

The cumulative incidence, relative risks (RR) and 95% CIs, period prevalence, median age at disease diagnosis and the prevalence of multimorbidity of 108 major physical and mental diseases were computed. All analyses were stratified by sex and age groups.

Results

The analysis included 684 455 individuals (54.8% females, mean age: 46.9), among whom 46.3% had multimorbidity, with a higher prevalence in females (47.6%) than males (44.9%). The chronological disease map revealed stark differences between females and males, with notable lower risk of obstructive sleep apnoea-hypopnoea syndrome (OSAHS, RR: 0.03, 95% CI: 0.01 to 0.11) for young adults, oesophageal cancer (RR: 0.02, 95% CI: 0.0 to 0.17) for mid-age adults and remarkable higher risk of lupus (RR: 8.8, 95% CI: 2.7 to 29.0) for older adults of females. Males exhibited an incidence surge in hypertension, diabetes, coronary disease and chronic obstructive pulmonary disease a decade earlier than females, while females had a life-long higher prevalence in immune-mediated diseases and urinary disorders. For the new incident diseases, the manifestation of eating disorders, anaemia and urinary incontinence was recorded 20 years earlier in females; whereas, males were diagnosed with hyperuricaemia, OSAHS and schizophrenia at younger ages.

Conclusions

The significant variations in disease nature and trajectory between sexes underscore the urgent needs for tailored prevention strategies and appropriate health resources allocation. Sex differences in disease profile should be considered to delay disease and multimorbidity progression, ultimately promoting health equity.

Asthma self-knowledge patient-reported outcome measures for the paediatric population with asthma: a systematic review protocol

Por: Goncalves · A. S. · Simoes · P. A. · Gama · J. M. R. · Jacome · C. · Maricoto · T.
Introduction

Asthma is a major personal and public health problem worldwide, with a significant impact on patients’ quality of life and health systems. The prevalence of asthma in children is 9.1% and in adolescents is 11%. Greater literacy among children is related to better asthma control. There are many validated Patient-Reported Outcome Measures (PROMs) related to asthma, but there are only a few, and no gold standard, to measure children and adolescents’ knowledge of asthma. Therefore, the purpose of this systematic review is to evaluate the most suitable asthma self-knowledge PROMs for the paediatric population with asthma.

Methods and analysis

The inclusion criteria will be children and adolescents diagnosed with asthma (population), validated PROMs about asthma self-knowledge (intervention), between each PROM (comparison) and measurement properties (outcome) (validity, reliability, interpretability and responsiveness). The search process will be conducted in PubMed, Web of Science, EMBASE and SCOPUS. The risk of bias evaluation will be done independently by two authors with the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist, and the quality of evidence will be evaluated based on the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethics approval is not applicable for this study since the data that will be collected are secondary data and are already in the public domain. The results will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42024577500.

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