More than half of older adults living with Alzheimer’s disease and related dementias (ADRD) never receive a formal diagnosis, and when a diagnosis occurs, it is often years after symptom onset. Primary care clinicians are ideally positioned to detect ADRD early; however, current workflows lack scalable tools that support systematic identification and follow-up. The Passive Digital Marker (PDM), a machine learning model that uses structured electronic health record (EHR) data, can identify patients at elevated risk for ADRD without adding burden to clinicians. This protocol outlines a feasibility study to develop and evaluate a patient-informed secure messaging intervention paired with PDM-based risk stratification to enhance patient engagement in cognitive assessment in primary care settings.

This will be a non-randomised pilot study conducted across 12 single health system primary care clinics. The PDM will be applied to EHR data to identify patients aged ≥65 years who are at high risk for ADRD. High-risk patients will receive a co-designed secure message prior to and after upcoming primary care visits encouraging follow-up evaluation with a trained nurse, the Brain Health Navigator (BHN). The primary objectives are to: (1) determine the feasibility of applying the PDM to EHR data across 12 primary care clinics; (2) assess the feasibility of engaging patients identified as positive on the PDM through secure text messaging prior to a primary care encounter and (3) evaluate engagement with the BHN following secure text messaging. Study outcomes will assess the feasibility of implementing the PDM and secure messaging workflow, including identification of high-risk patients using the PDM, message delivery and patient engagement measured through message open rates, completion of cognitive concern questions and appointments scheduled with the BHN. Quantitative data will be analysed using descriptive statistics.

This study was deemed exempt as part of enhanced patient care. The findings will be disseminated through peer-reviewed publications, professional conferences, health system reports and public-facing communications.

NCT07016178.

To examine the relationships between erectile dysfunction (ED) and diabetes and related complications, metabolic syndrome (MetS) components and lower urinary tract symptoms (LUTSs) in a cohort of men seeking care for urinary urgency and other LUTSs.

Cross-sectional analysis of baseline data from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN II) Urinary Urgency Phenotyping study, which aimed to characterise subgroups of persons with urinary urgency.

Six clinical sites of the NIH/NIDDK-sponsored Symptoms of LURN, US.

305 men enrolled in the LURN II Urinary Urgency Phenotyping study who provided complete baseline erectile function data.

Erectile function was assessed using the erectile function domain of the International Index of Erectile Function (IIEF). MetS components, diabetes-related complications and LUTS severity were compared between men with and without ED.

Among 305 men with urinary urgency, 181 (59%) had ED. Men with ED were significantly older and more likely to have type 2 diabetes (25% vs 12%, p

These data suggest that diabetes as well as markers of metabolic dysfunction are important factors in ED in treatment-seeking men with urinary urgency and other LUTS. Studies evaluating the mechanisms contributing to these interactions are warranted for targeting effective prevention or treatment.

To compare the diagnostic accuracy of four available automated electronic medical record (EMR) retrieval methods, including a large language model (LLM)-assisted workflow, against manual chart adjudication for identifying cardiovascular events.

Retrospective diagnostic accuracy study.

Three sites within a single US tertiary health system.

Two adult cohorts with previously adjudicated cardiovascular outcomes were included. Cohort 1 included 2258 patients treated with immune checkpoint inhibitors, and Cohort 2 included 1426 patients who underwent transcatheter aortic valve replacement.

The reference standard was clinician manual chart adjudication. Outcomes included ischaemic stroke or transient ischaemic attack, myocardial infarction (MI), heart failure (HF) exacerbation or hospitalisation and a composite major adverse cardiovascular events (MACE) outcome. Automated retrieval methods included International Classification of Diseases (ICD) codes, primary diagnosis, problem list and a zero-shot LLM workflow. Area under the (receiver operating characteristic) curve (AUC), sensitivity, specificity and net reclassification improvement were assessed.

In Cohort 1, the LLM achieved the highest AUC for stroke (0.920; 95% CI 0.881 to 0.958), MI (0.938; 95% CI 0.905 to 0.971) and composite MACE (0.880; 95% CI 0.854 to 0.907), whereas ICD-based retrieval had a higher AUC for HF (0.882; 95% CI 0.845 to 0.918 vs 0.873; 95% CI 0.831 to 0.914). In Cohort 2, the LLM achieved the highest AUC for all evaluated outcomes: stroke (0.915; 95% CI 0.862 to 0.968), MI (0.928; 95% CI 0.839 to 1.000), HF (0.844; 95% CI 0.803 to 0.884) and composite MACE (0.862; 95% CI 0.829 to 0.895). In Cohort 1, differences in AUC between the LLM and ICD methods were not statistically significant across outcomes, whereas in Cohort 2 the LLM showed significantly higher AUC for stroke and composite MACE.

In this multisite retrospective validation study, the LLM-assisted workflow showed strong but context-dependent performance for identifying cardiovascular events from the EMR. Performance varied by outcome and cohort, and ICD-based retrieval remained competitive for some use cases. These findings support a complementary role for LLM-assisted extraction in retrospective cardiovascular outcomes research.

Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is diagnosed, current recommendations for clinical care are based primarily on expert consensus with a ’one size fits all’ approach to management. Detailed knowledge of genotype-phenotype associations and the impact of genetic modifiers is lacking, and due to strong ascertainment bias of children already diagnosed with cancer predominantly being tested for a CPS, the true cancer risk is likely overestimated.

The Childhood Cancer Predisposition Study (CCPS) is a multi-centre registry and biorepository for children and adolescents aged 0–21 years with a clinical or molecularly confirmed CPS and their family members (NCT04511806). The study objectives are to characterise the natural history of each CPS, correlate the natural history phenotype with CPS genotype, evaluate the efficacy of standard surveillance strategies and allow future investigation into the feasibility and effectiveness of novel surveillance strategies. The principal study question is whether adherence to recommended tumour surveillance guidelines is associated with earlier detection of tumours and/or improved survival. We will also address what barriers exist that prevent adherence to surveillance guidelines. Data collected from primary subjects includes detail about the CPS, genomic data, cancer history and family cancer history, as well as information about tumour surveillance. Required biospecimen collection includes germline DNA samples, with optional collection of serial blood and stool samples. Planned enrolment is 1050 primary subjects.

CCPS was reviewed and approved by a central IRB (WCG IRB 2020P002450) and the Research Ethics Board at The Hospital for Sick Children in Toronto (1000072286). Written informed consent is obtained from all participants. Data and specimens are available to qualified investigators by request to address specific research questions through a standardised research application process. In addition, de-identified data are available through the Pediatric Cancer Data Commons for exploration. Analysed data will be disseminated in peer-reviewed publications and at conferences including meetings inclusive of patient and family advocacy groups.

NCT04511806.

Sickle cell disease (SCD) is one of the most common inherited haemoglobinopathies worldwide and the most prevalent monogenic disorder in the UK. Real-world implementation of existing guidance remains variable particularly in emergency and community settings. The study aims to build national consensus among multidisciplinary stakeholders as a crucial first step towards standardising practice and improving outcomes.

Using a single-round modified Delphi methodology, a Steering Committee of six UK-based specialists identified key domains for discussion and generated 48 consensus statements relevant to the care of patients with SCD. Using a four-point Likert scale, a survey including all statements was disseminated among a wider audience of healthcare professionals (HCPs) to determine agreement. The threshold for agreement was set at ≥75%. Eligible participants for this study included National Health Service (NHS) haematologists (adult or paediatric) and clinical or community nurse specialists from across the UK.

In total, 112 completed surveys were received. Consensus (≥75% agreement) was achieved for 46 of 48 statements (96%), including 32 (67%) that reached ≥90% agreement. The strongest consensus (>95%) was observed in statements emphasising the need for: broader access to specialist clinics and multidisciplinary care, prioritisation of community-based management and prevention of end-organ damage, education of emergency department staff on acute SCD management and improved HCP understanding of the multisystem nature of SCD and its psychosocial impacts. Two statements (S37, S43) did not meet the threshold, both concerning variability in adherence to national guidelines and allocation of dedicated SCD funding.

A modified Delphi consensus achieved national multidisciplinary team expert recommendations to optimise NHS SCD care. These recommendations use expert opinion to clarify priorities, identify resource and education gaps, and aim to standardise practice for consistent, high-level patient care and robust outcome assessment.

Geriatric distal femur fractures are associated with mortality rates exceeding 20%, comparable to hip fractures. Traditional single implant fixation often requires weight-bearing restrictions that delay recovery. This pilot study aims to assess the feasibility of conducting a multicentre randomised controlled trial comparing dual vs single implant fixation for geriatric distal femur fractures.

This multicentre, prospective, randomised controlled pilot trial will enrol 80 participants aged 60 years or older with displaced distal femur fractures at five US level 1 trauma centres. Patients will be randomly allocated 1:1 to receive either single implant (lateral plate or retrograde nail) or dual implant (nail-plate or dual plate) fixation. All patients will be permitted immediate weight-bearing. The primary outcome is feasibility assessed through enrolment rate (80 patients in 12 months), protocol adherence (≥90%) and follow-up retention (≥85% at 12 months). Secondary outcomes include post-surgical mobility (AM-PAC, TUG), patient-reported outcomes (PROMIS-PF, PROMIS-29), mortality (90-day and 1 year) and complication rates. Analyses will be on an intention-to-treat basis.

The protocol was approved by the University of Utah Institutional Review Board (IRB_00149119) and IRBs at all participating centres. Written informed consent will be obtained from participants or legally authorised representatives. Findings will be disseminated through peer-reviewed publications and conference presentations.

NCT05292313.

Randomised controlled trials (RCTs) are essential to determine intervention effectiveness yet they often fail to capture how and why interventions succeed or fail in different contexts. Embedding a process evaluation alongside a clinical trial allows exploration of implementation processes, intervention fidelity and contextual influences. The CANFit trial is a basket-design RCT evaluating a personalised, remotely delivered exercise intervention for people diagnosed with breast, lung and bowel cancer with increased risk of recurrence. This embedded process evaluation aims to understand how individual, team and organisational factors influence intervention delivery and uptake.

A concurrent, mixed-methods process evaluation will be conducted using a hybrid type 1 design. Data will be collected from multiple sources, including participant and trainer questionnaires, semi-structured interviews, intervention adherence logs, trainer diaries and observations. Five core implementation outcomes, guided by Proctor’s framework—acceptability, appropriateness, fidelity, penetration and sustainability—will structure the evaluation. Quantitative data will be analysed descriptively and qualitative data will undergo framework analysis using both deductive and inductive coding. Data integration will occur through a convergent mixed-methods approach, using context-mechanism-outcome (CMO) configurations to refine programme theory.

Ethical approvals were obtained through Hull York Medical School (ID: 23/SS/0060) and the UK NHS Health Research Authority (ID: 327663). All participants will provide informed consent before taking part. Data will be handled according to General Data Protection Regulation and University of Hull data management policies. Findings will be disseminated through peer-reviewed publications, conference presentations, stakeholder reports and lay summaries for participants and the public.

ISRCTN97662203.

Dementia is a major global health problem with increasing prevalence. Hearing loss has been identified as the most modifiable risk factor for dementia. The Age-Related Cognition and Hearing (ARCH) study is a 3-year prospective, controlled, observational comparative cohort study comparing cochlear implants (Implants) and hearing aids (HAs) for reducing cognitive decline associated with age-related hearing loss (ARHL), based on patient-reported real-world outcomes of auditory function, cognitive performance, listening environment, social interaction and psychosocial well-being. Upon its completion in 2029, the ARCH study is expected to yield significant evidence regarding the comparative effects of two primary hearing interventions—Implants and HAs, to delay and ameliorate cognitive decline associated with ARHL.

210 older adults are divided into six study subgroups (N=35) with: (1) moderate to profound hearing loss or age-typical normal hearing, (2) use of Implants or HAs and (3) mild cognitive impairment (MCI) or normal cognition. Listeners in the HA groups have hearing loss that is consistent with Implant candidacy and qualification through Centers for Medicare & Medicaid Services in the USA. The primary study outcome is a 3-year change in real-time patient-reported outcomes collected while participants are in their natural listening environments using ecological momentary assessment (EMA) methodologies. Secondary outcomes include lab-based audiometric and neuropsychological testing, and patient-reported outcomes of social isolation, loneliness, depression, anxiety and quality of life.

Cross-sectional analyses will use factor analysis to reduce EMA items into domains, followed by regression and mixed-effects models to test group differences and identify specific EMA items driving those effects. Machine-learning approaches will complement these models by predicting outcomes, identifying key variables and uncovering data-driven patterns. Longitudinal mixed-effects models will assess how EMA factor scores and cognition change over time and whether real-world EMA experiences mediate cognitive trajectories. Additional analyses will compare real-time EMA responses with retrospective patient-reported outcome measures and laboratory-based cognitive and auditory assessments, with sample size adjusted for up to 10% attrition.

All study procedures follow institutional review board requirements and the Declaration of Helsinki at the University of Iowa (IRB# 202403385), with informed consent processes tailored to ensure understanding among participants with MCI. Study findings will be disseminated through a multi-tiered strategy aimed at maximising scientific, clinical and public health impact. Peer-reviewed manuscripts will be submitted to leading journals in audiology, geriatrics, cognitive ageing and public health, with interim and final results presented at national and international conferences and professional society meetings.

To evaluate the feasibility, acceptability and potential efficacy of the culturally adapted Educate, Nurture, Advise Before Life Ends (ENABLE) programme in Singapore for patients with heart failure (HF) and their family caregivers.

Non-blinded randomised wait-list controlled pilot study, using Simon’s randomised phase II trial design.

Specialist outpatient clinics in a tertiary cardiac centre in Singapore.

Patients had a diagnosis of American Heart Association Stage C or D HF, were symptomatic with New York Heart Association functional class 2 and above symptoms, had a prognosis of 6 months, a hospitalisation in prior 6 months and were on disease-directed HF management. Patients already known to palliative care (PC) were excluded. Recruited caregivers were family caregivers of patients.

ENABLE integrates PC early into HF care. It starts with a comprehensive PC assessment with a PC physician and nurse. This is followed by a series of nurse coach-led health coaching sessions for both patients and caregivers. After the completion of health coaching, participants would receive follow-up phone calls to review their coping up to 6 months post-enrolment.

Feasibility was defined by the proportion of approached patient-caregiver dyads who consented to participate and the proportion of participants who completed health coaching. Acceptability was defined by a score of at least 12 out of a maximum of 16 for the Client Satisfaction Questionnaire 4-Item Survey. Primary efficacy outcome measure was the change in patient quality of life (QOL) at 6 months as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) total score, with the target effect size (Cohen’s d) being at least 0.25 SD in favour of ENABLE. Other secondary outcomes included patient/caregiver anxiety and depression scores on the Hospital Anxiety and Depression Scale, spirituality scores on the Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing Scale and caregiver QOL on the Singapore Caregiver Quality of Life Scale.

Feasibility: recruitment was carried out from February 2022 to October 2023. We approached 164 patient-caregiver dyads and 60 patient-caregiver dyads (36.6%) consented. A total of 48 patients and 44 caregivers started on health coaching, of which 44 patients (91.7%) and 43 caregivers (97.7%) completed health coaching.

Acceptability: patients’ satisfaction was high, at 85.7% and 87.5% in the intervention and wait-list arm, respectively. Caregivers were similarly satisfied, at 100% and 87.5% in the two arms, respectively.

Efficacy: intervention-arm patients had a higher mean total KCCQ score at 6 months than wait-list-arm patients (difference in means=12.4; 95% CI 0.9 to 24.0; Cohen’s d=0.43). There was no difference in caregiver QOL changes between trial arms at 3 months and 6 months. Both patients and caregivers had improvements in anxiety at 3 months and sustained improvements in depression and spirituality at 6 months.

Proportion of participants who completed health coaching was high, though proportion of approached participants who consented was lower than expected. Our acceptability and efficacy targets were met. Further phase III testing is planned.

NCT05211882.

Respiratory syncytial virus (RSV) is a significant cause of respiratory infections in young children. Since 2021, RSV has been a notifiable disease in Australia. However, current surveillance systems focus on hospitalised RSV, with limited surveillance at a community level through primary care clinics. This approach only captures RSV requiring hospitalisation. Less severe illnesses, while not captured, may have significant social and economic impacts including the associated cost of care and absenteeism. The aim of this study is to establish an understanding of the broader burden of RSV in young children in a community setting.

The PATROL (Parents Actively Tracking RSV in Little Ones) project is a prospective longitudinal observational study of RSV and other respiratory viruses in children

Incidence rates of RSV illness and asymptomatic carriage will be calculated and compared with the incidence rate ratios of other respiratory viruses.

The Government of Western Australia Child and Adolescent Health Service Human Research Ethics Committee approved all study materials. Results and findings will be disseminated through manuscripts, conference abstracts and presentations, participant newsletters and appropriate general news media items.