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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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