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Analytical validation of a homologous recombination deficiency signature (HRDsig) in pan-tumor tissue samples

by Wenshu Li, Jeffrey A. Leibowitz, Shuoguo Wang, Louisa Walker, Chang Xu, Kuei-Ting Chen, Alexa B. Schrock, Jason Hughes, Nimesh Patel, Julia A. Elvin, Lauren L. Ritterhouse, Ethan Sokol, Garrett Frampton, Lucas Dennis, Bahar Yilmazel, Brennan Decker

Homologous recombination repair (HRR) is a cellular pathway for high-fidelity double strand DNA break repair that uses the sister chromatid as a guide to ensure chromosomal integrity and cell viability. Deficiency in the HRR pathway (HRD) can sensitize tumors to poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy, offering an avenue to identify patients who may benefit from targeted therapies. HRD signature (HRDsig) is a pan-solid-tumor biomarker on the FoundationOne®CDx (F1CDx®) assay that employs a DNA scar-based approach to calculate a score based on copy number features (e.g., segment size, oscillation patterns, and breakpoints per chromosome arm) and does not rely on HRR gene alterations, enabling detection of genomic and epigenetic mechanisms of HRD. After finalizing the HRDsig algorithm, analytical validation was conducted in a CAP-accredited, CLIA-certified laboratory on 278 solid tumor and normal tissue specimens. HRDsig results were compared with an independent HRD biomarker, defined by the presence of a reversion mutation restoring HRR gene function. In this evaluation, 100 HRD-positive and 126 HRD-negative samples showed a positive percent agreement of 90.00% and a negative percent agreement of 94.44%. The limit of detection (LoD) was estimated at 23.04% tumor purity, with the limit of blank (LoB) confirmed as zero in 60 normal tissue replicates. Reproducibility testing on 11 positive and 11 negative samples across multiple labs, reagent lots, and sequencers yielded agreement in 99.49% of positive and 99.73% of negative replicates. HRDsig status remained consistent in the presence of interfering substances, demonstrating 100% concordance in spiked samples. These validation results underscore the high analytical concordance, low false-positive rate, and overall robustness of HRDsig for reliable assessment of homologous recombination deficiency.

Development of a case definition for polycystic ovary syndrome using administrative health data: a validation study

Por: Salem · J. N. · Vettese · R. · Yamamoto · J. M. · Koshy · S. · Harrison · T. · Stephenson · N. · Ronksley · P. E. · Metcalfe · A. · Brennand · E. A. · Benham · J. L.
Objectives

To develop and validate a polycystic ovary syndrome (PCOS) case definition using administrative health data sources.

Design

A validation study.

Setting

Secondary care centre outpatient gynaecology clinic in Calgary, Alberta, Canada.

Participants

3951 electronic health records of women aged 18–45 years who presented to a gynaecology clinic in Calgary, Canada, between January 2014 and December 2019 were reviewed. We identified 180 patients with PCOS using the Rotterdam criteria. Participants were excluded if they were biologically male, pregnant at the time of the consultation, did not meet the date criteria or if their consultation note was missing. The chart data were connected to the Practitioner Claims and the Discharge Abstract Database by personal health number.

Primary and secondary outcome measures

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 68 case definitions for PCOS were estimated. Case definition performance was graded.

Results

Of the 68 case definitions tested, none had high validity. The best performing case definitions were: (1) ≥3 instances of International Classification of Diseases-9 code 256.4 (polycystic ovaries) with exclusion codes (sensitivity 23.89%, specificity 99.59%, PPV 74.14%, NPV 96.35%) and (2) 626.X (irregular menstruation), 704.1 (hirsutism) and ≥3 instances of code 256.4 with exclusion codes (sensitivity 2.78%, specificity 99.97%, PPV 83.33%, NPV 95.40%).

Conclusions

We identified several case definitions for PCOS of moderate validity with high PPV (>70%) for case ascertainment in PCOS research in jurisdictions with similar administrative health data. These case definitions are limited by low sensitivity, which should be considered when interpreting research findings.

Three infections, one fight: an implementation study to map needle prevalence and evaluate HIV, syphilis and hepatitis C prevention interventions in Regina, Saskatchewan - a protocol

Por: Eaton · A. D. · Rowe · M. W. · Varghese · S. M. · House · H. · Pang · N. · Kwan · S. · Ford · P. · Reddy · V. D. · Acoose · T. · Littleford · J. · Lang · K. · Foreman · E. S. · Sasakamoose · J. · Pandey · M. · Medeiros · P. · Loutfy · M. R. · Grace · D. · Brennan · D. J. · Zhao · K. · Shuper
Introduction

Saskatchewan is facing a public health crisis driven by high rates of HIV, syphilis and hepatitis C virus (HCV) infections, particularly among people who use drugs. Injection drug use is a major contributor to these syndemic infections, exacerbated by structural barriers such as stigma, poverty and limited culturally safe healthcare. Innovative, community-informed approaches are urgently needed to improve prevention, testing and linkage to care.

Methods and analysis

This study will implement a rapid assessment and response system in Regina, Saskatchewan, Canada, integrating geospatial mapping of community needle prevalence with pop-up interventions. Needle hotspot maps will be used to guide the deployment of community-based pop-up events offering point-of-care testing for HIV, syphilis and HCV, alongside education on pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). A convergent participatory mixed-methods design will be used to evaluate feasibility, acceptability and effectiveness, guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Quantitative data will assess changes in knowledge of PrEP and PEP, satisfaction with the intervention and report new diagnoses and participant demographics descriptively. A qualitative substudy will include 30 participants and will explore experiences with the intervention, barriers to care and perceptions of service delivery.

Ethics and dissemination

Ethical approval has been obtained from the research ethics board of the Saskatchewan Health Authority (#24–91). Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study may provide a model of community-based geospatial testing and education that could be scaled up and adapted elsewhere.

Registration

Open Science Framework https://doi.org/10.17605/OSF.IO/HVK3B

Assessing the efficacy, safety and utility of hybrid closed-loop glucose control compared with standard insulin therapy combined with continuous glucose monitoring in young people (>=16 years) and adults with cystic fibrosis-related diabetes (CL4P-CF s

Por: Kadiyala · N. · Coleman · R. · Lakshman · R. · Wilinska · M. E. · Brennan · A. · Lumb · A. · Holt · R. I. G. · Lau · D. · Yajnik · P. · Cheah · Y. S. · Safavi · S. · Felton · I. · MacGregor · G. · Clayton · A. · Lawton · J. · Rankin · D. · Churchill · S. · Adler · A. · Hovorka · R. · Boughto
Introduction

Cystic fibrosis-related diabetes (CFRD) is one of the most clinically impactful comorbidities associated with cystic fibrosis (CF). Current recommended management with insulin therapy is challenging due to variable daily insulin requirements and adds to the significant burden of self-management. This study aims to determine if hybrid closed-loop insulin delivery can improve glucose outcomes compared with standard insulin therapy with continuous glucose monitoring (CGM) in young people (≥16 years) and adults with CFRD.

Methods and analysis

This open-label, multicentre, randomised, two-arm, single-period parallel design study aims to randomise 114 young people (≥16 years) and adults with CFRD. Following a 2–3 weeks’ run-in period, during which time participants use a masked CGM, participants with time in target glucose range (3.9–10.0 mmol/L) 10.0 mmol/L), mean glucose and HbA1c. Other secondary efficacy outcomes include glucose and insulin metrics, change in forced expiratory volume in 1 s and body mass index. Safety, utility, participant experiences and participant-reported outcome measures will also be evaluated. The trial is funded by the National Institute for Health and Care Research.

Ethics and dissemination

Ethics approval has been obtained from East of England–Cambridge South Research Ethics Committee. Results will be disseminated by peer-reviewed publications and conference presentations, and findings will be shared with people living with CF, healthcare providers and relevant stakeholders.

Trial registration number

NCT05562492.

Application of the socio-ecological model to understand the drivers of excessive alcohol and salt consumption: a qualitative study in Ghana

Por: Mensah · J. P. · Akparibo · R. · Thomas · C. · Aryeetey · R. · Brennan · A.
Objectives

This study aims to identify the key factors driving excessive alcohol and salt consumption in Ghana, both of which are modifiable risk factors for diseases such as cardiovascular conditions and cancers. Using the socio-ecological model (SEM), we qualitatively examine stakeholder perspectives to gain a comprehensive understanding of the influences contributing to these unhealthy consumption patterns.

Design and methods

A qualitative study was conducted using semi-structured interviews. Transcripts were analysed thematically, with identified drivers mapped onto the corresponding levels of influence within the SEM.

Participants

The study included 21 purposively sampled stakeholders from government and academic institutions in Ghana, including policymakers, practitioners and researchers.

Results

Drivers of excessive salt and alcohol consumption were identified across all five levels of the SEM. At the intrapersonal level, disregard for health risks was a key factor. Community-level drivers included easy access to unhealthy foods and cultural norms promoting alcohol use at social events and salt in traditional dishes. At the societal and policy levels, inadequate regulation of the alcohol and food industries was found to reinforce lower-level drivers, further encouraging unhealthy consumption.

Conclusions

This study highlights the multilevel influences on alcohol and salt consumption, emphasising the interactions across SEM levels. It highlights that addressing unhealthy consumption is not solely a matter of personal responsibility, demonstrating that societal and policy factors play a significant role in shaping health and dietary behaviours. The findings underscore the need for comprehensive public health strategies that address influences at multiple levels to effectively reduce excessive alcohol and salt intake.

Continuous physiological monitoring for the detection of postoperative deterioration: a protocol for a multistage, multicentre, international, prospective cohort study

Por: Jiwa · A. · Cameron · M. M. · Ademuyiwa · A. O. · Adisa · A. · Aguilera Arevalo · M. L. · Bahrami Hessari · M. · Bhangu · A. · Brennan · P. M. · Clark · N. · Cresswell · K. · Czerwinska · I. · DAdderio · L. · Gunn · E. · Haque · P. D. · Ikegwuonu · T. · Lawani · I. · Morton · D. · Nganwa
Introduction

Intermittent physiological monitoring and early warning scores (EWS) are limited in their ability to detect deteriorating patients in a timely manner. Wearable physiological sensors allow continuous remote monitoring and may be more timely and accurate in the identification of those at risk, compared with manual collection. This study aims to determine if wearable physiological sensors can be used for the early detection of postoperative deterioration, while being acceptable to patients and healthcare staff.

Methods and analysis

This is a prospective observational cohort study that will recruit adults undergoing major surgery in Benin, India, Ghana, Guatemala, Mexico, Nigeria, Rwanda and the UK. Participants will wear wearable physiological chest and limb sensors before, during and after surgery for up to 10 days or until discharge. In this ‘shadow-mode’ study, continuous physiological observations collected using the devices will not be made available to clinical teams. No changes in participant care will result. Standard of care clinical data will be collected contemporaneously. Continuous sensor data will be used to design algorithms to predict deterioration and specific complications in this population. Usability and feasibility testing, through focus groups, interviews and questionnaires, will be undertaken with healthcare professionals and people undergoing surgery.

Ethics and dissemination

Our stakeholder panel are directly involved in all aspects of this study, which will be conducted in accordance with the principles of the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (ICH GCP) in addition to the principles of the ethics committee(s)/Institutional Review Boards (IRBs) who have reviewed and approved this study. Artificial intelligence (AI) prediction models will be reported in accordance with the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis+Artificial Intelligence (TRIPOD+AI) and Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI) reporting guidelines frameworks.

Trial registration number

NCT06565559.

Luminance and thresholding limitations of virtual reality headsets for visual field testing

by Changseok Lee, Liam Redden, Vivian Eng, Brennan Eadie

Purpose

To investigate the luminance capacity and achievable threshold levels of commercially employed virtual reality (VR) devices for visual field testing.

Methods

This two-part study included (1) a literature review of VR headsets used for perimetry with luminance data extracted from technical specifications in publications and manufacturers; and (2) empirical evaluation of three most employed VR headsets in the literature using a custom virtual testing environment.

Results

Three most employed VR devices for visual field testing were Pico Neo, Oculus Quest, and HTC Vive. The maximum reported luminance was 250 cd/m2 for the HTC Vive Pro. Information on luminance measurement was not consistently available, reporting only handheld luminance meters. Empirical measurements show that handheld luminance meters significantly overestimate luminance compared to standard spectroradiometers. Measured luminance varies significantly across aperture size and decreases for peripheral stimuli up to 30 degrees peripherally. Assuming conventional background of 10 cd/m2, the best performance with lowest possible thresholding was with HTC Vive at 16dB, corresponding to luminance of 80 cd/m2 centrally. Oculus Quest 2 and Pico Neo 3 had minimum threshold of 20dB.

Conclusion

Commercially available VR devices do not meet luminance requirements or threshold sensitivities for visual field testing. Current VR technology is not designed—nor has the capacity—to threshold at mid-to-low dB ranges, which limits accuracy in diagnosing and monitoring defects seen in glaucoma. Translational Relevance: This study highlights the technical limitations of current commercially available VR devices for visual field testing and significant variables in evaluating luminance performance in these devices.

Interventions delivered in healthcare settings to promote vaping cessation in children and young people (under the age of 18 years): a scoping review protocol

Por: Hoo Chuin Shen · M. · Gabriel · M. M. · Brennan · L. · Isba · R.
Introduction

Vaping among children and young people (CYP) has increased globally over the past decade, with rates stabilising in the UK in recent years. Factors such as curiosity, social influence, stress management and attractive flavours contribute to its popularity. Although the long-term health impacts are uncertain, vaping poses risks including nicotine dependence, cardiovascular and respiratory issues, and cognitive impairment, though evidence on long-term effects is still emerging. Despite established smoking cessation programmes for adults, tailored resources for vaping cessation among CYP remain scarce, particularly within healthcare settings, which offer unique opportunities for professional intervention and ongoing support. The objective of this review is to assess the extent and nature of available literature on interventions delivered in healthcare settings to support vaping cessation among CYP under the age of 18 years.

Methods and analysis

This scoping review will include studies targeting CYP under the age of 18 years, specifically focusing on interventions delivered within healthcare settings. Studies outside healthcare contexts or those without healthcare provider involvement will be excluded. Additionally, interventions delivered solely to parents or carers will not be considered.

A comprehensive search will be conducted in MEDLINE, Embase, Web of Science, Cochrane Library and CINAHL from January 2004 to present, with additional grey literature from sources including grey literature repositories and Google Scholar. Results will be imported into Rayyan for screening, with two independent reviewers assessing studies for inclusion. Data extraction will include study design, population characteristics (including explicit age ranges, specifically CYP under 18 years), intervention details and outcomes. A descriptive synthesis will map study characteristics, while thematic analysis will identify intervention themes and healthcare contexts.

Ethics and dissemination

Ethics approval is not required for this secondary analysis. Findings will be disseminated through publication, conference presentations and shared with public health stakeholders.

How does trauma informed care education for paediatric healthcare professionals impact self-reported knowledge and practice: an integrative review by Thorton et al

Por: Brennan · G.

EBN Contemporary Nursing Education on: Thornton et al. 2025, How does trauma informed care education for paediatric healthcare professionals impact self-reported knowledge and practice. An integrative review. Nurse Education in Practice. 82.

Implications for nursing education

  • Healthcare professionals reported improved awareness and understanding of trauma-informed care (TIC) and self-efficacy in applying it in practice.

  • Nurse educators should continue to develop robust evaluation of TIC educational interventions.

  • Context

    Psychological trauma is a major public health concern, with high rates of exposure among the population. Within paediatric healthcare settings, exposure can be substantial.1 Such experiences are not always ‘one off’ events but are closely related to adverse childhood experiences (ACEs) such as abuse by caregivers, family dysfunction, parental mental health issues, substance abuse or domestic abuse. Such exposure can have a significant impact on child development, resulting in significantly poorer physical and mental...

    Nurse practitioners' use of diagnostic imaging: A scoping review

    Abstract

    Aim

    To explore the nature and extent of peer-reviewed literature related to the use of diagnostic imaging by nurse practitioners (NPs) to inform future practice and research.

    Background

    Nurse practitioners undertake advanced assessment, diagnosis, and management of patients, including requesting and interpretation of diagnostic imaging. It is unclear what evidence exists related to the quality use of radiological investigations by NPs in recent years.

    Design

    A scoping review based on the steps suggested by the Joanna Briggs Institute.

    Methods

    A structured review of the databases Medline, CINAHL and Embase was undertaken using the keywords and MESH terms ‘nurse practitioner’, ‘medical imaging’, ‘diagnostic imaging’, ‘scan’ and ‘radiography’. Only English language articles were included, and no date limit was applied. Database review was completed on 30 May 2021.

    Results

    Eight themes were identified—country and clinical context, requesting diagnostic imaging, performing diagnostic imaging, image-guided interventions, interpreting diagnostic imaging, training education and knowledge, impact on resource usage and comparison with medical practitioners. There were more studies across a greater breadth of clinical specialties and imaging modalities in the United States than in other countries. Nurse practitioner practice is frequently benchmarked against that of medical colleagues. There is a paucity of studies focusing on educational preparation and the lack of relevant university curricula for NPs around diagnostic imaging.

    Conclusion

    There are significant gaps in the evidence outside of the United States across several of the identified themes. Further studies are needed to explore NP access to and use of diagnostic imaging and to understand the barriers and facilitators to this.

    Relevance to Clinical Practice

    Studies from four countries were included in this review. The evidence suggests that, where studied, nurse practitioners (NPs) can safely and appropriately request and interpret plain x-rays in the emergency and minor injuries setting. Further research is needed to evaluate the educational needs of NPs in relation to diagnostic imaging and their use of advanced imaging techniques, particularly outside of the United States.

    Patient or Public Contribution

    No patient or public contribution.

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