NIHR Exeter Clinical Research Facility

BackgroundPatient-reported outcome measures (PROMs) are key elements of assessing the efficacy of perioperative pain management. Here, we aimed to capture the association of 10 individually reported aspects of patient's specific impression of change since surgery (PSIC) related to four outcome domains of a previously defined core outcome set, relative to the patient's global impression of change (PGIC). We further evaluated the influence of type of surgery, sex, preoperative baseline characteristics, and satisfaction with pain management on PGIC.MethodsThis exploratory analysis used the PROMPT NIT-1 study data (2661 patients, 18 sites, four surgery types: total knee arthroplasty, sternotomy, breast cancer surgery, or endometriosis surgery). Male and female adults were included. All PROMs were assessed on postoperative day 3. We used ordinal regression models with PGIC as a dependent variable and PSICs as independent variables.ResultsThe overall model achieved a pseudo-R2 of 0.55 (relative domain contributions: pain intensity 55%, self-efficacy 19%, adverse events 15%, and pain-related interference of physical functioning 10%). Pain-related worrying and depression had no association with the PGIC, whereas anxiety, preoperative pain, opioid intake, low satisfaction with and wish for more treatment, low treatment agency, and overall dissatisfaction were associated with less improvement after surgery. Receiving information about treatment was associated with greater improvement on the PGIC.ConclusionsAlthough all four domains contributed to PGIC after surgery, pain intensity was the most important. These findings highlight the importance of both managing postoperative pain and optimising patient experience by addressing self-efficacy, adverse events, and pain-related interference of physical functioning.Clinical trial registrationNCT 03834922

ABSTRACTObjectiveTo identify predictors of loneliness and social isolation experienced by people with dementia at baseline and over time.MethodsUsing data from the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort study (2014–2018), we examined the prevalence and predictors of loneliness and social isolation in 1547 people with mild‐to‐moderate dementia over 24 months. Loneliness was measured using the six‐item De Jong Gierveld Scale at baseline and 24 months and social isolation by the six‐item Lubben Social Network Scale at baseline, 12 and 24 months. Generalised linear mixed effects models examined possible predictors of loneliness and social isolation including individual characteristics, depression, cognition, cultural participation, and neighbourhood characteristics.ResultsAt baseline 35.4% of people with dementia were categorised as being lonely and 28.8% as socially isolated, increasing to 39.3% and 32.0% 2 years later. Over the 24‐month follow‐up none of these predictors were associated with changes in social isolation scores. Only perceived neighbourhood trust was associated with change in loneliness longitudinally. At baseline, depressive symptoms, living alone, smaller social networks and lower neighbourhood trust were associated with greater loneliness. Cross‐sectionally, loneliness and lower cognitive ability were associated with greater social isolation, and greater cultural participation, more green and blue spaces nearby and higher neighbourhood trust were associated with lower social isolation scores.ConclusionsThe findings highlight the importance of the local environment and cultural participation for people with dementia. Enhancing interactions with the local neighbourhood through initiatives such as dementia friendly communities may help to reduce loneliness and social isolation.

BackgroundIncisional and non-incisional ventral hernias are common and important causes of symptoms, functional restriction, and complications, with significant potential to impact upon quality of life. The goals of hernia repair are to treat, prevent or improve these. However, outcomes of surgery remain relatively poor with significant gaps within the evidence base, which may be due to inconsistent use of outcome measures. The aim of this study was to appraise outcome reporting in the recent literature of randomized controlled trials (RCTs).ObjectivesThis scoping review aimed to map and categorize the outcome measures reported in RCTs of incisional and non-incisional ventral hernia repair.Eligibility criteriaAll RCTs assessing any intervention related to incisional, primary, or recurrent ventral hernia repair between2015 and 2025 were included.Source of evidenceA literature search was performed of the PubMed, EMBASE (1974 to present), and Cochrane Central Register of Controlled Trials databases in November March 2025.Charting methods Data was extracted independently by two reviewers. All outcomes reported by the included studies were identified and recorded.Results118 RCTs were included. Their outcomes were mapped into five main broad categories. The commonest outcomes used were short-term operative complications (72.9%), hernia recurrence (59.3%), pain (57.6%), and quality of life (33.9%). Patient-reported outcomes were measured in 78 (66.1%) randomized controlled trials, of which 15 assessment tools were identified; 11 were generic, and 4were hernia-specific. There was considerable heterogeneity in how and when these endpoints were assessed and defined.ConclusionThis scoping review found considerable differences in outcome reporting in contemporary RCTs of incisional and non-incisional ventral hernia. These have significant implications for translating evidence into practice, and its synthesis, and support the need for a core outcome set in this field. However, we identified areas such as abdominal wall function which are infrequently reported and require consideration.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10029-025-03553-y.

Structured Objective:Mild Behavioral Impairment (MBI) is a syndrome of late-life-onset persistent neuropsychiatric symptoms. Anticholinergic medication is commonly prescribed in older adults. Both MBI and anticholinergic exposure are associated with increased dementia risk. We sought to understand the association of anticholinergic burden (ACB) with MBI.Design, Setting, participants:We mapped ratings on the Neuropsychiatric Inventory Questionnaire to the MBI checklist (MBI-C) using an established algorithm to define MBI status in cognitively unimpaired individuals in the National Alzheimer’s Coordinating Center database. We then assessed the association between time-varying ACB ratings and risk of incident MBI.Results:4865 participants met inclusion criteria and were followed for a mean (SD) of 5.64 (3.92) years. ACB scores ranged from 0–11. 63.3% of participants had a score of 0, 27.7% had a score of 1–2, and 9% had a score of ≥3. Higher maximum total ACB score was associated with a higher likelihood of developing MBI (p=<0.001). When assessed as a time varying covariate, ACB score was associated with incident MBI (HR 1.12, 95% CI 1.05–1.19, p=<0.001). This association remained significant when adjusted for 10-year mortality risk.Conclusions:MBI risk should be considered when prescribing anticholinergic medication in older adults.

Epidemiological, PET imaging, genome-wide association and animal research suggests inflammation contributes to Alzheimer's disease (AD) and other dementias, however there is no consensus on its precise contribution. Human and animal studies show acute systemic inflammation, arising from infection, fracture or co-morbid inflammatory disease, accelerate dementia. ASCRIBED aimed to investigate the relationship between acute hip fracture, inflammation and brain injury in dementia. Participants were recruited with dementia and hip fracture, those with hip fractures but no dementia, and a control group of individuals with dementia but no acute illness or injury. Cerebrospinal fluid (CSF) and blood samples were collected to measure inflammatory markers and brain injury biomarkers. We recruited from 37 UK hospital sites, drawing CSF and blood from participants with dementia and hip fracture (n=191), participants with no dementia and hip fracture (n=218), participants with confusion and hip fracture (n=80) and a Norwegian cohort of community-dwelling participants with dementia (n=181). Most participants were women (68%) across the groups. APOE3/E3 was the commonest genotype in UK samples (mean 56%). Multi-morbidity as measured by the Charlson index was highest in the dementia fracture group. Despite the stable dementia group showing the expected CSF elevation in phosphoTau (p<0.001) and reduction in CSF Ab1-42 (p<0.001) compared to all other groups, the axonal damage marker neurofilament light chain (NFL) was significantly higher in those with hip fracture than in stable dementia and was highest in those with hip fracture and dementia (p<0.001). CSF NFL levels were correlated most strongly with blood CSF barrier permeability, as measured by Qalbumin (p<0.001). Our findings show hip fracture leads to an increase in axonal injury, significantly beyond that observed in patients with stable dementia. This acute injury appears more severe in those with existing dementia. Additionally, NFL levels were correlated with blood CSF barrier permeability which may suggest a link between axonal damage and BBB disruption. Further research is needed to elucidate the underlying mechanisms of this acute brain injury and explore potential therapeutic interventions.

ABSTRACTBackgroundPeriods of muscle disuse occur during hospitalization, illness or the recovery from (sports) injury and lead to a rapid loss of muscle mass and the development of insulin resistance. Salbutamol is a fast‐acting β2‐adrenoreceptor agonist that may improve muscle protein synthesis and insulin sensitivity during experimental muscle disuse and thereby attenuate or preserve muscle mass; however, this has not yet been tested as a standalone intervention.MethodsEffects of salbutamol treatment on muscle metabolism were studied in a randomized controlled trial using a human forearm immobilization model (n = 20). Before and after immobilization for 2 days, we measured whole‐body glucose disposal, forearm glucose uptake and amino acid kinetics during fasting and hyperinsulinaemic–hyperaminoacidaemic–euglycemic clamp conditions using forearm balance and L‐[ring‐2H5]‐phenylalanine infusion. Underlying mechanistic effects were studied as well using a complementary murine hindleg immobilization model (2 weeks) using tracer approaches (i.e., deuterated water and 14C‐labelled phenylalanine) and molecular analyses (e.g., RNA‐seq and western blot).ResultsIn humans, salbutamol enhanced insulin‐stimulated glucose disposal on the whole‐body level (+21%, p = 0.010) but was unable to ameliorate the immobilization‐induced decrease in forearm glucose uptake. Salbutamol decreased the efflux of amino acids from the immobilized forearm, indicating increased muscle protein synthesis and/or inhibition of breakdown. However, this did not affect the immobilization‐induced impairment of amino acid net balance in both postabsorptive (−250%) and clamp conditions (−261%, both p = 0.031). In agreement, in mice, salbutamol increased cumulative muscle protein synthesis (+0.87%, p < 0.001) but did not result in a net gain of muscle mass upon immobilization due to an accompanying increase in muscle protein turnover (+13%, p < 0.001). Molecular analyses revealed immobilization inhibited salbutamol's effects on the muscle transcriptome, specifically the muscle contraction pathway (−2.1 normalized enrichment score, p < 0.001).ConclusionsSalbutamol increases muscle mass and glucose uptake, although these effects are limited to active but not inactive muscles. This demonstrates that the mechanism of action and efficacy of β2‐adrenoreceptor signalling are hampered upon immobilization, which offers potential for a combined treatment intervention of reintroducing muscle contraction and salbutamol administration to improve muscle mass and clinical outcomes during episodes of physical inactivity.

This project explores the feasibility of setting up a neuropsychiatric de-identified database (DiD) and a Research Register (RR) to collect, analyse, monitor and systematically report clinical data for people with intellectual disabilities (PwIDs) and epilepsy. A multicentre project designed to collect de-identified data from clinical records at three adult ID specialist services in England and Wales and to develop an RR of PwID and epilepsy. Patients added to the DiD will be identified from patient clinic lists, clinic letters, in-house databases and electronic systems. Patients to be added to the RR will also be identified through attendance for regular review at clinic appointments. The collected data will be entered into the Research Electronic Data Capture (REDCap) database. Personal details of PwID and their consultees will also be collected from participants who consent to be on the RR. Around 600 PwID and epilepsy (200 per site) will be added to the DiD at the three sites, while around 45-60 participants (15-20 per site) are anticipated to be added to the RR. Data analysis will involve using descriptive statistics to summarise feasibility outcomes, such as screening and recruitment rates, as well as the completeness of the collected data. The characteristics of the participants (demographic, ID classification, clinical, epilepsy history and antiseizure medication) will be summarised descriptively. Progression will be assessed using the Red/Amber/Green stop-go criteria to determine if a national register should be created. Ethical approval (24/NW/0210) has been obtained from the Northwest-Haydock Research Ethics Committee and the University of Plymouth Faculty Research Ethics and Integrity Committee (reference no. 5284). The project is funded by Jazz Pharmaceuticals as an independent investigator-initiated support grant and, as such, has received independent peer review. NCT06780501.

<h3>Introduction</h3> Idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP) cause significant morbidity and mortality. Quantitative computed tomography (qCT) may provide radiomic biomarkers to assist in the prognostication and disease monitoring of these conditions. We aimed to investigate a prognostic role for qCT in fHP and IPF. <h3>Methods</h3> This retrospective, observational, multicentre study analysed electronic records of patients with an ILD multidisciplinary diagnosis of fHP or IPF. Patients required ≥1 HRCT and ≥2 pulmonary function tests (PFTs) between 2015 and 2022. Data were censored on 30/01/2025. Demographics, PFTs, bronchoalveolar lavage (BAL), CT scans, and survival data were recorded. Brainomix e-Lung used deep-learning to derive radiomic biomarkers from anonymised scans. Correlations between PFTs and qCT was assessed using Pearsons correlation. For patients with baseline paired PFTs and qCT and ≥12 months follow-up Cox proportional hazards models were used to assess association of qCT, age, sex, smoking status, Charlson comorbidity index and baseline PFTs with progression-free survival (time to 10% FVC decline, 15% TLCO decline, or death). <h3>Results</h3> 155 patients with fHP and 216 with IPF were included. Of the CT scans, 485/558 (fHP) and 388/456 (IPF) had successful quantitative analysis, and 304/558 (fHP) and 338/456 (IPF) had paired PFTs (within 90 days of scan acquisition). Forced vital capacity (FVC)% predicted and transfer factor (TLCO)% predicted correlated with e-Lung’s radiomic weighted reticulovascular score (WRVS) in both fHP (r=-0.56 and r=-0.49 respectively, both p&lt;0.05) and IPF (r=-0.52 and r=-0.57 respectively, both p&lt;0.05) across all paired scans. In patients with fHP, BAL lymphocytosis was negatively correlated with WRVS (n=45, r=-0.352, p=0.02). Table 1 summarises patients included in the Cox proportional hazards analysis, WRVS was independently associated with progression-free survival in both IPF and fHP (fHP: HR 1.08, 95%CI 1.03–1.12, p&lt;0.05; IPF: HR 1.08, 95%CI 1.02–1.15, p&lt;0.05). <h3>Conclusions</h3> WRVS correlates with PFTs and is negatively associated with lymphocytosis on BAL, highlighting the potential for WRVS to assess non-fibrotic burden in fHP patients. Baseline WRVS is associated with progression-free survival in both IPF and fHP and may aid prognostication in these patient groups.

PurposeHernia repairs are one of the commonest operations performed in the world. In Europe and the United States of America more than half of patients undergoing hernia surgery are overweight or obese; body weight is therefore key modifiable risk factor before surgery. We aimed to identify, appraise, and synthesise the randomized controlled trial (RCT) evidence for any weight loss interventions before any form of hernia surgery.MethodsA search was performed in April 2025 of the PubMed, EMBASE and CENTRAL databases. Meta-analysis was performed using random effects to assess mean difference in weight, and fixed effects for odds ratio of complications. Bias was assessed using the Cochrane Rob2 tool. Certainty effect was assessed using GRADE methodology. This review was registered with PROSPERO (ID 1024784).Results1,707 studies were screened, 20 retrieved, and 4 reports of 3 RCTs included. A total population of 219 patients largely underwent ventral hernia repair, although 2 RCTs also included patients undergoing non-hernia surgery. Interventions comprised very low calorie diets (VLCD), and a multidisciplinary programme. Meta-analysis for VLCD did not show a reduction in weight loss (3.64 kg [95% confidence interval −2.07 – 9.35]) or complications [odds ratio 0.36 (0.1–1.28)]. Risk of bias was “high,” and certainty of effect “very low.”DiscussionDespite the prevalence and importance of obesity in patients undergoing elective hernia repair, and the popularity of weight loss as part of prehabilitation, the randomized evidence of how to effect weight loss, and whether this translates into an improvement in clinical outcomes is minimal. This highlights the urgent need for large and robust RCTs to determine if weight loss before hernia repair is effective in improving outcomes for patients, and how this is best achieved.