The prognostic value of left atrial (LA) strain in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully elucidated. Therefore, this study investigated the prognostic value of LA strain in HFrEF patients in relation to all-cause mortality.

A total of 822 echocardiograms from HFrEF patients admitted to a heart failure clinic were analysed offline. To calculate left atrial reservoir strain (LA RS) and left atrial contractile strain (LA CS), LA two-dimensional speckle tracking was performed in the 4-chamber, 2-chamber and 3-chamber view. The end-point was all-cause mortality. The association between LA strain parameters and outcome was examined using Cox regression.

The median follow-up time was 40 months and follow-up was 100% complete. During follow-up, a total of 137 patients (16.7%) died of all causes. In a final multivariable model adjusted for clinical and echocardiographic parameters including global longitudinal strain, LA RS and LA CS were significantly associated with all-cause death during follow-up (LA RS, HR 0.96, 95% CI 0.92 to 0.99, p=0.014, pr. 1% increase) (LA CS, HR 0.95, 95% CI 0.92 to 0.98, p=0.002, pr. 1% increase).

When added to the final multivariable model, both LA RS and LA CS contributed with incremental prognostic value as determined by C-statistic (LA RS: C-stat difference 0.007, 95% CI 0.000 to 0.020, p=0.050) (LA CS: C-stat difference 0.009, 95% CI 0.000 to 0.023, p=0.030).

In HFrEF patients, LA RS and LA CS were associated with all-cause mortality and contributed incremental prognostic value in addition to established prognostic measures.

Lifestyle changes—such as adopting healthy nutrition and increasing physical activity—are essential for alleviating symptoms in patients with knee osteoarthritis (OA) and overweight, with weight loss being a key outcome of these changes. Since 2019, healthcare professionals (HCPs) in the Netherlands have been able to refer these patients to a reimbursed combined lifestyle intervention (CLI). This study aims to identify determinants affecting CLI implementation for individuals with knee OA and overweight from both patient and HCP perspectives.

Semistructured interviews were conducted in a qualitative study with 23 individuals with knee OA and overweight and 16 HCPs (general practitioners (GPs) and lifestyle coaches). Interviews were transcribed verbatim and coded independently by two researchers using the updated Consolidated Framework for Implementation Research (CFIR).

Primary care, including GPs and lifestyle coaches from the Greater Rotterdam region in the Netherlands.

23 individuals with knee OA and overweight and 16 HCPs (GPs and lifestyle coaches).

Determinants were explored within four CFIR domains: innovation, outer setting, inner setting and individuals. Key facilitators included recognition of the programme’s potential, strong social support and positive participant–coach relationships. Major barriers involved the absence of an exercise component, financial constraints limiting its inclusion, scepticism among GPs about care quality, limited expertise of lifestyle coaches addressing OA-specific needs and difficulties adapting the programme to participants’ diverse knowledge levels and health literacy.

To improve the implementation of the CLI for patients with knee OA, it is essential to incorporate a tailored exercise component, strengthen lifestyle coaches’ expertise, address financial barriers and build trust among GPs through education and clear communication of programme outcomes. Tailoring the CLI to better meet participant needs is crucial to ensure its long-term effectiveness and sustainability as a treatment for individuals with knee OA and overweight.

Netherlands Trial Registry (NL9355).

To test the agreement and usability of a novel quality appraisal tool: A MeaSurement Tool to Assess systematic Reviews of Prognostic Factor studies (AMSTAR-PF).

Observational study.

14 appraisers of varied experience levels and backgrounds, including undergraduate, master’s and PhD students, postgraduate researchers, research fellows and clinicians.

Eight systematic reviews were rated by all reviewers using AMSTAR-PF.

Planned measures included intrapair and inter-pair agreement using Cohen’s and Fleiss’ kappa, time of use and time to reach consensus. Interrater agreement was an added measure, and Gwet’s agreement coefficient was calculated and presented due to its greater stability across agreement levels. The percentage of intrapair agreements identical or one category apart was also presented.

Interrater agreement averaged 0.59 (range 0.21–0.90), inter-pair agreement 0.61 (range 0.24–0.91) and intrapair agreement 0.75 (range 0.45–0.95) across the domains, with agreement for the overall rating 0.46 (95% CI 0.30 to 0.62) for interrater agreement, 0.46 (95% CI 0.17 to 0.74) for inter-pair agreement and 0.68 (range of averages 0.22–1.00) for intrapair agreement. The majority (60.7%) of intrapair ratings were identical, with 94.6% of final ratings either identical or only one category different for the overall appraisal. The time taken to appraise a study with AMSTAR-PF improved with use and averaged around 34 min after the first two appraisals.

Despite some variance in agreement for different domains and between different appraisers, the testing results suggest that AMSTAR-PF has clear utility for appraising the quality of systematic reviews of prognostic factor studies.

To develop and externally validate a two-stage machine learning framework that integrates polygenic risk and clinical variables for early identification of individuals at risk of developing type 2 diabetes.

We conducted a prospective prediction study using data from the All of Us Research Program for model development and the UK Biobank for external validation. Two models were constructed. Stage 1 used gradient boosted decision trees (XGBoost) with cross validation, automated hyperparameter optimisation and class weighting to predict 5-year incident type 2 diabetes using demographic, clinical and polygenic predictors. Stage 2 incorporated glycated haemoglobin or fasting glucose measurements to refine risk estimates. Model interpretation used SHapley Additive exPlanations values and permutation importance, and logistic regression and random forest models served as comparators. Discrimination of all models was compared using the DeLong test.

The Stage 1 model achieved an area under the receiver operating characteristic curve (AUROC) of 0.81 in All of Us and 0.82 in UK Biobank, performing significantly better than the phenotype-only model in UK Biobank (DeLong p=1.05x10^–⁷⁶). Higher polygenic risk quartiles were associated with increased incidence of type 2 diabetes in both cohorts (global ² p

A two-stage machine learning framework that integrates genetic and clinical information can support personalised screening for type 2 diabetes across diverse populations. The approach demonstrated robust performance across cohorts and offers a practical structure for early risk identification.

Most patients with health conditions necessitating time off work consult in primary care. Offering vocational advice (VA) early within this setting may help them to return to work and reduce sickness absence. Previous research shows the benefits of VA interventions for musculoskeletal pain in primary care, but an intervention for a much broader primary care patient population has yet to be tested. The Work And Vocational advicE feasibility study tested patient identification and recruitment methods, explored participants’ experiences of being invited to the study and their experiences of receiving VA.

A mixed method, single arm feasibility study comprising both quantitative and qualitative analysis of recruitment and participation in the study.

Primary care.

The study included participant follow-up by fortnightly Short Message Service text and 6-week questionnaire. Stop/go criteria focus on recruitment and intervention engagement. The semistructured interviews explored participants’ experiences of recruitment and receipt and engagement with the intervention.

19 participants were recruited (4.3% response rate). Identification of participants via retrospective fit-note searches was reasonably successful (13/19 (68%) identified), recruitment stop/go criteria were met with ≥50% of those eligible and expressing an interest recruited. The stop/go criterion for intervention engagement was met with 16/19 (86%) participants having at least one contact with a vocational support worker. Five participants were interviewed; they reported positive experiences of recruitment and felt the VA intervention was acceptable.

This study demonstrates that delivering VA in primary care is feasible and acceptable. To ensure a future trial is feasible, recruitment strategies and data collection methods require additional refinement.

NCT04543097.

Shoulder osteoarthritis most commonly affects older adults, causing pain, reduced function and quality of life. Total shoulder replacements (TSRs) are indicated once other non-surgical options no longer provide adequate pain relief. Two main types of TSRs are widely used: anatomic TSR (aTSR) and reverse TSR (rTSR). It is not clear whether one TSR type provides better short- or long-term outcomes for patients, and which, if either, is more cost-effective for the National Health Service (NHS).

RAPSODI-UK is a multi-centre, pragmatic, two-parallel arm, superiority randomised controlled trial comparing the clinical- and cost-effectiveness of aTSR versus rTSR for adults aged 60+ with a primary diagnosis of osteoarthritis, an intact rotator cuff and bone stock suitable for TSR. Participants in both arms of the trial will receive usual post-operative rehabilitation. We aim to recruit 430 participants from approximately 28 NHS sites across the UK. The primary outcome is the Shoulder Pain and Disability Index (SPADI) at 2 years post-randomisation. Outcomes will be collected at 3, 6, 12, 18 and 24 months after randomisation. Secondary outcomes include the pain and function subscales of the SPADI, the Oxford Shoulder Score, health-related quality of life (EQ-5D-5L), complications, range of movement and strength, revisions and mortality. The between-group difference in the primary outcome will be derived from a constrained longitudinal data analysis model. We will also undertake a full health economic evaluation and conduct qualitative interviews to explore perceptions of acceptability of the two types of TSR and experiences of recovery with a sample of participants.

Ethics committee approval for this trial was obtained (London - Queen Square Research Ethics Committee, Rec Reference 22/LO/0617) on 4 October 2022. The results of the main trial will be submitted for publication in a peer-reviewed journal and using other professional and media outlets.

ISRCTN12216466.

To understand healthcare professionals’ views on current physiotherapy service provision in children with congenital heart disease (CHD), how physiotherapy could be better used post-cardiac surgery and perceived barriers to service expansion.

Cross-sectional survey using a one-off self-completed online questionnaire, with open and closed questions, in June–August 2024.

Each of the 12 level 1 paediatric cardiac surgical centres in the UK National Health Service and Children’s Health Ireland.

Healthcare professionals providing clinical care to children undergoing cardiac surgery.

80 responses were obtained, with at least one response from each centre. Healthcare professionals conduct motor, developmental and functional evaluations across all age groups, with referrals to physiotherapy primarily based on physical examination (39, 87%). They expressed dissatisfaction with community physiotherapy services (64, 81%) compared with inpatient services (29, 36%), although they indicated that expanding services would positively impact patients and families. There is a lack of consensus regarding intervention frequency, duration and which patient groups should be prioritised. Respondents identified a lack of funding as the primary barrier to service expansion (76, 95%). Reported barriers for families included volume of medical appointments (69, 86%), transportation (66, 83%) and finances (62, 78%).

Healthcare professionals appreciate the positive impact physiotherapy can have on post-surgical management of children with CHD. The importance of expanding services was emphasised. However, to effectively support clinical practice, it is crucial to understand which patient groups should be prioritised and at what stage, as well as determining the optimal amount of physiotherapy that positively impacts patient outcomes.

The SupportBack 2 randomised controlled trial (RCT) compared the clinical and cost-effectiveness of an internet intervention supporting self-management versus usual primary care in reducing low back pain (LBP)-related disability. In this study, we aimed to identify and understand key processes and potential mechanisms underlying the impact of the intervention.

This was a nested qualitative process evaluation of the SupportBack 2 RCT (ISRCTN: 14736486 pre-results).

Primary care in the UK (England).

46 trial participants experiencing LBP without indicators of serious spinal pathologies (eg, fractures, infection) took part in telephone interviews at either 3 (n=15), 6 (n=14) or 12 months (n=17) post randomisation. Five physiotherapists who provided telephone support for the internet intervention also took part in telephone interviews.

An internet intervention ‘SupportBack’ supporting self-management of LBP primarily through physical activity and exercise delivered in addition to usual care, with and without physiotherapist telephone support.

Data were analysed thematically, applying a realist logic to develop context-mechanism-outcome configurations.

Four explanatory themes were developed, with five context-mechanism-outcome configurations. Where benefit was reported, SupportBack appeared to work by facilitating a central associative process where participants linked increases in physical activity or exercise with improvements in LBP, then continued to use physical activity or exercise as key regulatory strategies. Participants who reported little or no benefit from the intervention appeared to experience several barriers to this associative process, including negative expectations, prohibitive beliefs about the cause of LBP or functional limitations preventing engagement. Physiotherapists appeared to provide accountability and validation for some; however, the remote telephone support that lacked physical assessment was viewed as limiting its potential value.

Digital interventions targeting physical activity and exercise to support LBP self-management may rely on mechanisms that are easily inhibited in complex, heterogeneous populations. Future research should focus on identifying and removing barriers that may limit the effectiveness of digital self-management support for LBP.

Most clinical practice guidelines (CPGs) for assessing and managing people’s chronic pain focus on specific pain conditions, body sites or life course stages. This creates complexity for clinicians making care choices in the absence of a diagnosis and/or where a person experiences more than one pain condition. Specific to this context is the ICD-11 classification of chronic primary pain where an experience of pain cannot be better accounted for by another condition. CPGs for chronic primary pain, agnostic to condition or body part, may support clinicians towards best pain care since many of the principles of person-centred chronic pain care are transdiagnostic. The two aims of this systematic review are to (1) identify and appraise CPGs for chronic primary pain, relevant across the life course and (2) map the CPG content against a pain care priority framework to evaluate the extent to which the CPG content aligns with the priorities of people with lived chronic pain experience.

We will systematically search nine scholarly databases, the Epistemonikos database and international and national guidelines clearinghouses. CPGs published within 2015–2025, in any language, that offer recommendations about assessment and/or management of chronic primary pain for people of any age, excluding hospitalised inpatients or institutionalised populations, will be included. Pairs of reviewers will independently screen citations for eligibility and appraise CPG quality and implementation potential using the Appraisal of Guidelines for Research and Evaluation (AGREE)-II and the AGREE-Recommendations Excellence tools, respectively. Data extraction will include the citation and scope characteristics of each CPG, methods used to develop recommendations, verbatim recommendations, guiding principles or practice information and narrative excerpts related to the GRADE Evidence-to-Decision (EtD) considerations (or equivalent). We will use the PROGRESS-PLUS framework as a checklist to identify whether determinants of health equity were considered by guideline developers. CPG recommendations will be organised according to common topics and categorised in a matrix according to strength and direction. Qualitative content analysis will be used to synthesise excerpts relating to GRADE EtD considerations (or equivalent), and we will map extracted data against an established chronic pain care priority framework to determine the extent to which the CPGs align with values and preferences of people with lived experience. Interpretation will be informed by an interdisciplinary Advisory Group, including lived experience partners.

Ethical approval is not required for this systematic review. Results will be disseminated through publication in an open-access peer-reviewed journal, through professional societies, and integrated into education curricula and public-facing resources. Reporting will be consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

CRD420251000482.

In 2022, the WHO conditionally recommended the use of treatment decision algorithms (TDAs) for treatment decision-making in children

Within the Decide-TB project (PACT ID: PACTR202407866544155, 23 July 2024), we aim to generate an individual-participant dataset (IPD) from prospective TB diagnostic accuracy cohorts (RaPaed-TB, UMOYA and two cohorts from TB-Speed). Using the IPD, we aim to: (1) assess the diagnostic accuracy of published TDAs using a set of consensus case definitions produced by the National Institute of Health as reference standard (confirmed and unconfirmed vs unlikely TB); (2) evaluate the added value of novel tools (including biomarkers and artificial intelligence-interpreted radiology) in the existing TDAs; (3) generate an artificial population, modelling the target population of children eligible for WHO-endorsed TDAs presenting at primary and secondary healthcare levels and assess the diagnostic accuracy of published TDAs and (4) identify clinical predictors of radiological disease severity in children from the study population of children with presumptive TB.

This study will externally validate the first data-driven WHO TDAs in a large, well-characterised and diverse paediatric IPD derived from four large paediatric cohorts of children investigated for TB. The study has received ethical clearance for sharing secondary deidentified data from the ethics committees of the parent studies (RaPaed-TB, UMOYA and TB Speed) and as the aims of this study were part of the parent studies’ protocols, a separate approval was not necessary. Study findings will be published in peer-reviewed journals and disseminated at local, regional and international scientific meetings and conferences. This database will serve as a catalyst for the assessment of the inclusion of novel tools and the generation of an artificial population to simulate the impact of novel diagnostic pathways for TB in children at lower levels of healthcare. TDAs have the potential to close the diagnostic gap in childhood TB. Further finetuning of the currently available algorithms will facilitate this and improve access to care.

Patients with stage III non-small cell lung cancer (NSCLC) are at high risk of developing post-treatment recurrences (50–78%) during follow-up. As more effective treatments are now available, especially for patients with oligometastatic disease, earlier detection of recurrences may prolong survival and health-related quality of life (HRQOL). With the use of 2'-deoxy-2'-[¹⁸F]fluoroglucose positron emission tomography/CT ([¹⁸F]FDG PET/CT) during follow-up, recurrences may be detected earlier. Therefore, the primary objective of this study is to compare the 3-year overall survival of patients with stage III NSCLC during follow-up surveillance with [¹⁸F]FDG PET/CT versus follow-up with conventional CT (usual care). Secondary objectives address the number, location and timing of recurrences, as well as HRQOL, cost-effectiveness and patient experiences of PET/CT scans.

In this multicentre randomised controlled clinical trial, 690 patients with stage III NSCLC (8th edition International Association for the Study of Lung Cancer (IASLC) Tumor, Nodes, Metastasis (TNM) classification) who completed curative intended treatment and started follow-up care (which may include adjuvant therapy) will be randomised 1:1 to either the intervention ([¹⁸F]FDG PET/CT) or the control group (CT). Patients will undergo follow-up scans during visits at 6, 12, 18, 24 and 36 months. Data will be collected using validated questionnaires, electronic case report forms and data extractions from the electronic health records. Additionally, blood samples will be collected, and interviews will be conducted.

The study protocol has been approved by the Medical Ethical Committee of the Radboudumc and review boards of all participating centres. Written informed consent will be obtained from all participants. Study results will be published in international peer-reviewed scientific journals and presented at relevant scientific conferences. Data will be published in a data repository or other online data archive.

NCT06082492.

While survival rates following neonatal surgery for congenital heart disease (CHD) have improved over the years, neurodevelopmental delays are still highly prevalent in these patients. After correcting for the CHD subtype, the severity of developmental impairment is dependent on multiple factors, including intraoperative brain injury, which is more frequent and more severe in those undergoing aortic arch repair with deep hypothermic circulatory arrest (DHCA). It is proposed that brain injury may be reduced if cooling is stopped at the point of electrocerebral inactivity (ECI) on electroencephalogram (EEG), but there is limited evidence to support this as few centres perform perioperative EEG routinely. This study aims to assess the feasibility of EEG monitoring during neonatal aortic arch repair and investigate the relationship between temperature and EEG to inform the design of a future clinical trial.

Single-centre prospective observational cohort study in a UK specialist children’s hospital, aiming to recruit 74 neonates (≤4 weeks corrected age) undergoing aortic arch repair with DHCA. EEG will be acquired at least 1–3 hours before surgery, and brain activity will be monitored continuously until 24 hours following admission to intensive care. Demographic, clinical, surgical and outcome variables will be collected. Feasibility will be measured by the number of patients recruited, data collection procedures, technically successful EEG recordings and adverse events. The main outcomes are the temperature at which ECI is achieved and its duration, EEG patterns at key perioperative steps and neurodevelopmental outcomes at 24 months postsurgery.

The study was approved by the Yorkshire and The Humber Sheffield National Health Service Research Ethics Committee (20/YH/0192) on 18 June 2020. Written informed consent will be obtained from the participant’s parent/guardian prior to surgery. Findings will be disseminated to the academic community through peer-reviewed publications and presentations at conferences. Parents/guardians will be informed of the results through a newsletter in conjunction with local charities.