Earlier heart failure (HF) diagnosis in the community could allow timely treatment initiation and prevent unnecessary hospitalisation, but identifying those at risk remains challenging. We aimed to summarise the performance of risk prediction models for a new diagnosis of HF.

Systematic review of multivariable incident HF risk prediction models in the community setting.

MEDLINE and Embase were searched from inception to 9 November 2023.

Observational, community-based studies reporting prediction model performance for incident HF within a 5-year time horizon.

Two reviewers independently screened and extracted data. Where possible, C-statistics (or area under the receiver operating characteristic curve) with 95% CIs were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool and certainty of evidence by the Grading of Recommendations, Assessment, Development and Evaluation.

Eighteen studies described 45 prediction models, 27 used traditional statistical methods and 18 applied machine learning. Most (39/45) demonstrated acceptable discrimination (C-statistic >0.70). Overall, C-statistics ranged from 0.675 to 0.954, typically with narrow 95% CIs. External validation was performed for 31 models, but only two—the modified PCP-HF models for white men and women—were validated in three cohorts, the highest among all the models. Exploratory random-effects meta-analysis of these models showed pooled C-statistics of 0.82 (95% CI 0.82 to 0.82) for men and 0.85 (95% CI 0.82 to 0.88) for women, indicating excellent discrimination but more heterogenous performance among women. Model performance was at high risk of bias due to unreported or inappropriate handling of missing data, and the certainty of evidence was very low.

Risk prediction models for a new diagnosis of HF in the community performed well, but were at high risk of bias and lacked external validation. Future model development requires appropriate data sources, robust handling of missing data, external validation and clinical testing to assess their impact on earlier HF diagnosis and outcomes.

CRD42022347120.

Parkinson’s disease (PD) is a common neurodegenerative disease, which has extensive pathology that critically includes the loss of midbrain dopaminergic neurons. This loss leads to debilitating motor features such as bradykinesia and rigidity, as well as some non-motor symptoms. Intracerebral dopamine cell transplants have been explored for many years as a new approach to treating PD and initially used human fetal ventral mesencephalic tissue with inconsistent results, related in part to major logistical challenges in sourcing enough tissue of the right quality and the limited possibilities for quality control and standardisation. Dopaminergic neurons can now be derived reliably from human stem cell sources, which may overcome some of the challenges associated with fetal tissue transplantations.

STEM-PD is a multi-centre, single-arm, dose-escalation, first-in-human advanced therapy investigational medicinal product (ATIMP) trial in Europe using a cell product that consists of dopaminergic neural progenitors derived from the RC17 human embryonic stem cell line. The aim of the study is to assess the safety, tolerability and feasibility of intraputamenal transplantation of this cell product in patients with moderately advanced PD. Eight participants will be recruited from two sites, Skånes University Hospital (Lund, Sweden) and Cambridge University Hospital (Cambridge, UK). The primary outcome of the trial is safety and tolerability, assessed by the number and nature of adverse events and serious adverse events, and the absence of space-occupying lesions on cranial MRI, in the first 12 months following transplantation. Secondary and exploratory outcomes, including clinical measures, changes in anti-Parkinson’s medication and measures of graft survival using positron emission tomography imaging, will be assessed at both 12 and 36 months post-grafting.

Ethical approval was obtained from the Swedish Ethical Review Authority (EPM dnr 2021-06945-01) and South Central - Oxford A Research Ethics Committee (reference 23/SC/0243). Clinical Trial Authorisation was given by the Swedish Medical Products Agency (Dnr: 5.1-2022-57953) and the Medicines and Healthcare products Regulatory Agency for clinical trials authorisation (reference CTA 40773/0001/001-0001). Authorisation for transfer to Clinical Trial Regulation (EU) 536/2014 was given by the Swedish Medical Products Agency (Dnr: 5.1.1-2024-100773). Potential participants will receive verbal and written information about the trial and written informed consent will be obtained prior to enrolment. A lay summary of the results of the trial will be uploaded to the trial website which is publicly accessible. Trial results will be published in peer-reviewed journals.

NCT05635409.

Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities.

The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness.

Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments.

ACTRN12625001050448.

To explore the longitudinal experience of taking part in a physiotherapy-led exercise adherence programme as part of the OsteoPorosis Tailored exercise adherence INtervention (OPTIN) trial.

Longitudinal qualitative study using semi-structured interviews analysed with reflexive thematic analysis—an interpretive approach.

UK National Health Service.

12 participants with vertebral fragility fracture (VFF) within the exercise adherence intervention arm of the OPTIN trial (n=63 in each arm). Interviews were undertaken with each participant at three time points: (1) within the first 2 weeks of initial assessment, (2) at the end of the 16-week intervention and (3) a year post-baseline.

We distilled five themes. (1) One size does not fit all: this focuses on the importance of a physiotherapist individualising the exercise programme and how participants adapt it into their lives. (2) My mind and body can be in conflict or work together: this spotlights the strong link between one’s emotional and mental state with their physical state, and how they can work to positively or negatively affect exercise adherence behaviour. (3) Expanding my circle of support: this revolves around the need for support systems beyond family and friends to the physiotherapist and other people with osteoporosis. (4) Transitioning from an exercise programme to a lifestyle change: this encompasses a longitudinal perspective of the exercise programme tapering, becoming intermittent or dropping off after a year, then being replaced by sustained lifestyle changes. (5) Moving from fear to empowerment: this explores the fear and loss of former identity after VFF diagnosis transforming into hope, confidence and empowerment through knowledge, advice and coping strategies.

Findings highlight the need to work with mind and body to empower lifestyle changes and the importance of educating, tailoring, empathising and allying with the participant—all critical areas clinicians can target when treating patients with VFFs.

ISRCTN14465704.

Targeted biologic therapies have transformed outcomes for individuals with psoriasis, a common immune-mediated inflammatory skin disease. The widespread use of these highly effective treatments has led to a growing number of individuals with clear or nearly clear skin remaining on continuous, long-term treatment. Personalised strategies to minimise drug exposure may sustain long-term disease control while reducing treatment burden, associated risks and healthcare costs. This study aims to evaluate the feasibility of a definitive pragmatic effectiveness trial of two personalised dose minimisation strategies compared with continuous treatment (standard care) in adults with well-controlled psoriasis receiving the exemplar biologic risankizumab.

This is a multicentre, assessor-blind, parallel group, open-label randomised controlled feasibility trial in the UK, evaluating two personalised biologic dose minimisation strategies for psoriasis. 90 adults with both physician-assessed and patient-assessed clear or nearly clear skin on risankizumab monotherapy for ≥12 months will be randomised in a 1:1:1 ratio to (1) patient-led ‘as-needed’ treatment, where risankizumab is administered at the first sign of self-assessed psoriasis recurrence, (2) therapeutic drug monitoring-guided treatment, with personalised dosing intervals determined using a pharmacokinetic model or (3) continuous treatment as per standard care, for 12 months. Participants will be invited to submit self-reported outcomes and self-taken photographs every 3 months using a bespoke remote monitoring system (mySkin app) and will attend an in-person assessment at 12 months. They may also request additional patient-initiated follow-up appointments during the trial if needed. The primary outcome is the practicality and acceptability of the two personalised biologic dose minimisation strategies, assessed as a composite measure including recruitment and retention rates, adherence to the assigned strategies and acceptability to both patients and clinicians. The feasibility of collecting healthcare cost and resource utilisation data will also be evaluated to inform a future cost-effectiveness analysis. A nested qualitative study, involving semistructured interviews with patients and clinicians, will explore perspectives on the personalised biologic dose minimisation strategies. These findings will inform the design of a future definitive trial.

This study received ethical approval from the Seasonal Research Ethics Committee (reference 24/LO/0089). Results will be disseminated through scientific conferences, peer-reviewed publications and patient/public engagement events. Lay summaries and infographics will be codeveloped with patient partners to ensure the findings are accessible for the wider public.

ISRCTN17922845.

Current guideline-recommended antibiotic treatment durations for ventilator-associated pneumonia (VAP) are largely standardised, with limited consideration of individual patient characteristics, pathogens or clinical context. This one-size-fits-all approach risks both overtreatment—promoting antimicrobial resistance and adverse drug events—as well as undertreatment, increasing the likelihood of pneumonia recurrence and sepsis-related complications. There is a critical need for VAP-specific biomarkers to enable individualised treatment strategies. The Ventilator-associated pneumonia Biomarker Evaluation (VIBE) study aims to identify a dynamic alveolar biomarker signature associated with treatment response, with the goal of informing personalised antibiotic duration in future clinical trials.

VIBE is a prospective, observational, case-cohort study of 125 adult patients with VAP in Michigan Medicine University Hospital intensive care units. Study subjects will undergo non-bronchoscopic bronchoalveolar lavage on the day of VAP diagnosis (Day 1) and then on Days 3 and 5. Alveolar biomarkers (quantitative respiratory culture bioburden, alveolar neutrophil percentage and pathogen genomic load assessed via BioFire FilmArray polymerase chain reaction) will be assessed. An expert panel of intensivists, blinded to biomarker data, will adjudicate each patient’s Day 10 outcome as VAP clinical cure (control) or treatment failure (case). Absolute biomarker levels and mean-fold changes in biomarker levels will be compared between groups. Data will be used to derive a composite temporal alveolar biomarker signature predictive of VAP treatment failure.

Ethical approval was obtained from the University of Michigan Institutional Review Board (IRB #HUM00251780). Informed consent will be obtained from all study participants or their legally authorised representatives. Findings will be disseminated through peer-reviewed publications, conferences and feedback into clinical guidelines committees.

To assess the feasibility of conducting a definitive randomised controlled trial (RCT) to test the clinical and cost-effectiveness of a tailored exercise intervention compared with usual care for people aged 80 years and older with hip and/or knee osteoarthritis (OA) and comorbidities.

Two-arm, parallel-design, multicentre, pragmatic, feasibility RCT.

Four National Health Service outpatient physiotherapy services across England.

Adults aged 80 years and over with clinical hip and/or knee OA and ≥1 comorbidity.

Participants were randomised 1:1 via a central web-based system to be offered: (1) a 12-week tailored exercise programme or (2) usual care. Participants and outcome assessors were not blinded to treatment allocation.

(1) Ability to screen and recruit participants; (2) retention of participants at 14-week follow-up; (3) intervention fidelity (proportion of participants who received ≥4 intervention sessions as per protocol) and (4) participant engagement (assessed by home exercise adherence).

Between 12 May 2022 and 26 January 2023, 133 potential participants were screened, of whom 94 were eligible. The main reasons for ineligibility were symptoms not consistent with hip or knee OA (10/39, 25.6%) or already having had a physiotherapy appointment (8/39, 20.5%). 51 of 94 (54%) eligible participants were recruited. Participants had a mean age of 84 years (SD 3.5), 31 (60.8%) were female and 96.1% reported their ethnicity as White British (n=49/51). 45 of 51 participants (88%) provided outcome data at the 14-week follow-up time point. Four or more intervention sessions were attended by 13/25 (52%) participants. Home exercise log completion declined over time: 6/23 participants (26.1%) returned completed exercise logs for all 12 weeks. The median number of days home exercises were recorded each week was 5 (range 0–7).

This study demonstrated that a definitive trial would be feasible. Before proceeding, modifications to ensure recruitment of a diverse population and intervention fidelity should be addressed.

ISRCTN75983430.

Palmoplantar pustulosis (PPP) is a rare, debilitating inflammatory skin disease involving painful pustules on the palms and soles. Janus kinase (JAK) inhibitors target pathways relevant to PPP disease biology but also confer a risk of major adverse cardiovascular events and malignancy in certain ‘at risk’ individuals; this includes those with PPP given prevalent smoking and cardiovascular risk factors in the PPP population. The feasibility of JAK inhibitor therapy for PPP requires assessment prior to a randomised controlled trial evaluation of drug efficacy and safety for this indication.

The ‘Janus kinase inhibitors in palmoplantar pustulosis: a mixed-methods feasibility’ trial is an open-label, single-centre, single-arm, mixed-methods feasibility trial of JAK inhibition in PPP (REC reference: 24/NE/0147; ISRCTN61751241). Participants (n=20) will receive 8 weeks of treatment with the JAK inhibitor upadacitinib (‘Rinvoq’, 30 mg, once daily). Qualitative semistructured interviews (up to n=40) will be undertaken with trial participants, trial decliners and healthcare professionals. The primary outcome will be a composite assessment of feasibility across three domains: recruitment, adherence and acceptability, using a mixed-methods analysis approach. Secondary objectives include the identification of trial recruitment optimisation strategies, using the ‘Quintet Recruitment Intervention’, and the generation of an indication of effect size on disease severity (measured using the Palmoplantar Pustulosis Psoriasis Area and Severity Index) to inform future sample size calculations. Historic placebo control data from the Anakinra for Pustular Psoriasis: Response in a Controlled Trial (National Institute of Health and Social Care reference: 13/50/17; Research Ethics Commitee reference: 16/LO/0436) will be used as the effect size comparator. Study recruitment will be undertaken over a 24-month period, commencing in November 2024.

This study has been approved by the Newcastle North Tyneside 2 Research Ethics Committee, 24/NE/0132. Our findings will inform the feasibility of a future adequately powered RCT evaluating the efficacy of JAK inhibitor therapy in PPP.

ISRCTN61751241.