Sheffield Teaching Hospitals NHS Foundation Trust

Major trauma is a leading cause of death and disability. Specialised care in major trauma centres has been associated with improved outcomes and prehospital triage tools are used to ensure injured patients are treated in the right place and the right time. However, there is a trade-off between under- and over-triage, and this study aimed to externally validate current and newly developed major trauma triage tools. A diagnostic case-cohort study was performed between November 2019 and February 2020 in 4 English regional trauma networks as part of the Major Trauma Triage Study (MATTS). The accuracy of 22 adult major trauma triage tools, including 3 newly developed MATTS tools was evaluated. Consecutive patients with acute non-trivial injury presenting to participating ambulance services were included and matched to data from the English national major trauma database. Theoretical accuracy was examined, with index tests assessed according to objective ambulance service data, regardless of the final triage decision or hospital destination. The primary reference standard was a consensus definition of serious injury that would benefit from expedited major trauma centre care. The case-cohort sample consisted of 2,607 patients, including 928 primary reference standard positive patients. The population weighted prevalence of major trauma meeting the primary reference standard definition was 3.1% (95% CI 2.3-4.0). Four optimally performing triage tools were identified with Pareto decision analysis: the Trauma score (sensitivity 0.1, specificity 0.99), MATTS specific tool (sensitivity 0.37, specificity 0.95), MATTS balanced tool (sensitivity 0.58, specificity 0.87), and the MATTS sensitive tool (sensitivity 0.72, specificity 0.76). This finding was unchanged in subgroup analyses of different age-groups and injury mechanisms; secondary analyses examining alternative reference standards (ISS ≥ 16, US consensus definition); and sensitivity analyses exploring missing data. Four optimal triage tools, demonstrating a trade-off between sensitivity and specificity, were identified by this validation study. The choice of ideal tool will depend on prevalence of major trauma, and valuation of false positive and false negative cases. Further prospective investigation of real-life triage tool performance, including compliance and clinical judgment, is necessary.

Facioscapulohumeral muscular dystrophy (FSHD) is a common hereditary myopathy causing progressive muscle weakness. FSHD has substantial impacts on function and health-related quality of life (HRQoL). Patient-reported outcome measures (PROs) are used to assess HRQoL, yet their suitability for FSHD remains unclear. (1) identify PROs used to assess HRQoL in adults with FSHD; (2) evaluate the evidence for their measurement properties; and (3) develop a conceptual HRQoL framework for FSHD. A systematic review was conducted in accordance with COSMIN and PRISMA-COSMIN guidelines (PROSPERO: CRD42024605345). Two-stage searches across seven databases (including MEDLINE, Embase, and CINAHL, last updated July 2025) identified PROs assessing HRQoL in FSHD and studies evaluating their measurement properties. Eligibility criteria included publicly available, multi-item self-report PROs scored using established systems. Screening, data extraction, and quality appraisal were performed in duplicate. Measurement properties were rated using COSMIN standards and graded with the COSMIN-modified GRADE approach. Item content of the PROs was examined, mapped to an existing framework, and subsequently refined with people living with FSHD to develop a novel HRQoL framework for FSHD (QUAL-FSHD). Fifty-six development papers and 40 research studies were included in the review, 37 studies reported data on psychometric properties. Sixty-six PROs/subscales were included. Most had evidence limited to content validity (i.e., development papers in non-FSHD populations) and construct validity. Only the Upper Extremity Functional Index (UEFI) had data across five measurement properties, though overall evidence quality was very low to moderate. Responsiveness was assessed in nine PROs, with five determined to be ‘sufficient’. The QUAL-FSHD framework comprises seven themes and 44 subthemes. Mapping of the PROs found 21% (n = 14) covered aspects of physical, psychological, and social functioning, with no instrument covering all subthemes. Current publicly available HRQoL PROs used in FSHD exhibit significant gaps in content coverage and psychometric evidence to support their use in the condition. The QUAL-FSHD framework provides a structured, stakeholder-informed model for evaluating HRQoL in FSHD. There is an urgent need for future research to establish content validity, psychometric performance, and acceptable respondent burden of existing PROs to ensure accurate assessment of HRQoL outcomes in FSHD. Not applicable.

<h3>Background</h3> Oral candidiasis (OC) is common in palliative care, causing significant morbidity. Treating and preventing OC may improve quality of life. Palliative care patients often have poor performance status, multiple comorbidities, immunosuppression, limited prognosis, and polypharmacy. Existing guidelines are consensus-based, highlighting the need for stronger evidence. We conducted a systematic review to answer the question: ‘How effective are interventions for OC in palliative care patients?’ <h3>Methods</h3> We searched EMBASE, MEDLINE, and CINAHL from inception to 2025 for studies on OC treatment in palliative care patients. All study types were included except case series, editorials, and opinion pieces. Screening and data extraction were performed independently by paired reviewers. Due to study heterogeneity, results are presented narratively. The study was registered with PROSPERO [CRD42023341857]. <h3>Results</h3> Of 2,352 articles, 20 underwent full-text screening; 7 met inclusion criteria. Four interventions were reported with specific results: oral care regimens (n=2), nystatin (n=2), fluconazole (n=2), and miconazole (n=1). One study tested all the above interventions but did not report these separately. No RCTs were found. The methods limit conclusions; allowing for this, oral care regimens reduced candida on swab testing. Nystatin studies were conflicting: one showed benefit and one no effect. Fluconazole was effective, including single-dose use. A 1976 study supported miconazole. Many excluded studies focused on disease-specific populations without reporting palliative patients separately, limiting application to the general palliative care population. <h3>Conclusions</h3> Evidence for OC interventions in general palliative care is limited. Good oral care should remain a priority, but robust RCTs are needed to guide practice. Until then, guidelines should consider disease-specific approaches where evidence may be stronger.

<h3>Background</h3> Nausea and vomiting are commonly experienced symptoms in palliative care and can have a significant impact on a patient’s quality of life. In some patients, nausea and vomiting can persist despite use of multiple antiemetics. NK1 antagonists, aprepitant and fosaprepitant, are used for chemotherapy-induced nausea and vomiting. Evidence for their use in palliative care is currently limited to case reports in adults and a small case series in children. We have trialled these drugs in cases of intractable nausea and conducted a service evaluation of practice. <h3>Method</h3> We evaluated all hospice in-patients who received an NK1 antagonist since 2021. IPOS score for nausea and vomiting were routinely recorded at three time points: prior to starting, immediately after starting and the last recorded score. Qualitative data showing subjective evidence of benefit, as documented in the clinical notes, was also recorded. The frequency of additional antiemetics was noted for the 24-hour period immediately before and after the first dose. <h3>Results</h3> Seven patients received aprepitant; two received both aprepitant and fosaprepitant. Qualitative documentation showed that eight of the nine patients experienced an improvement in symptoms. Where patients tried aprepitant and fosaprepitant, both showed similar benefits. All patients used fewer additional antiemetics in the 24-hour period immediately after first dose. IPOS score before and immediately after taking aprepitant showed nausea improved in 25% of patients and vomiting improved in 12.5%. IPOS score before and immediately after fosaprepitant showed improvement in nausea in 50% of patients and vomiting in 100%. One patient receiving aprepitant refused to complete IPOS questionnaire. <h3>Conclusion</h3> NK1 antagonists may have a role for intractable nausea and vomiting in palliative care, particularly when other antiemetics have failed to control symptoms. Studies should incorporate subjective and prescribing data in addition to outcome measures.

Pharmacotherapy combinations have been shown to improve survival and reduce hospitalisations in adults with chronic heart failure with reduced ejection fraction (HFrEF); however, their cost-effectiveness when used as first-line treatment remains uncertain. A lifetime cohort Markov model was developed from the perspective of the NHS in England to assess the cost-effectiveness of five first-line pharmacotherapy combinations: (i) angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker (BB) (NICE-recommended treatment at the time of analysis); (ii) ACEI/ARB, BB and mineralocorticoid receptor antagonists (MRA); (iii) angiotensin receptor-neprilysin inhibitor (ARNI), BB and MRA; (iv) ACEI/ARB, BB, MRA and sodium-glucose cotransporter-2 inhibitor (SGLT2i); and (v) ARNI, BB, MRA and SGLT2i. Baseline hospitalisation and mortality rates were informed by real-world data, while treatment effects (HRs) were derived from a review of randomised controlled trials. Among individuals able to tolerate an ACEI, the combination of ACEI, BB, MRA and SGLT2i (cost, £12 124; quality-adjusted life years (QALYs), 5.72) was found to be the most cost-effective first-line treatment option with an incremental cost-effectiveness ratio (ICER) of £7699.Among individuals unable to tolerate an ACEI, the combination of ARNI, BB, MRA and SGLT2i (cost, £18 950; QALYs, 6.04) was found to be the most cost-effective first-line treatment option with an ICER of £15 821. The next most cost-effective first-line treatment option was the combination of ARB, BB, MRA and SGLT2i (cost, £11 842; QALYs, 5.59). These findings were primarily driven by the greater relative QALY gain of ARNI compared with ARB. This study demonstrates that a first-line quadruple pharmacotherapy combination is cost-effective compared with a stepwise approach for treating people with HFrEF, suggesting that wider adoption of early initiation of quadruple pharmacotherapy may improve health outcomes and optimise healthcare resource use.

In the United Kingdom and Sweden, men aged 65 are offered screening for Abdominal Aortic Aneurysm (AAA). Men with small AAA enter a surveillance programme to monitor growth until the AAA is large enough for referral for treatment. Some men develop anxiety related to having an AAA or being in surveillance. The original aim was to develop and assess the acceptability of a new intervention to help men in surveillance manage anxiety. As the study progressed, the aim changed to developing an information booklet to address men's uncertainties about AAA and surveillance because uncertainties might lead to anxiety. An intervention development study was undertaken, following guidance in three phases: 1. Identifying need using surveys of screening staff and men, and qualitative interviews with men and family members; 2. Co-design of an intervention using a literature review, programme theory development, and two workshops with men, family members, and a patient representative; 3. Assessing the acceptability of the intervention using a telephone survey of 23 men in AAA surveillance. Although the original aim was to develop an intervention to help men manage anxiety, men and screening staff identified the need for an information-based intervention to address men's uncertainties about AAA. Published evidence identified that uncertainty about health conditions or treatment can lead to anxiety, so the intervention taken forward was an information booklet to address men's uncertainties about AAA. A 16-page A5 booklet was developed with men and their family members, addressing why men had to wait for AAA to become large before referral for treatment, the risk of rupture for different sizes of AAA, and how to reduce the risk of rupture. In the telephone survey, 20/23 men in the AAA surveillance who read the draft booklet found it helpful because it addressed their uncertainties. They suggested minor refinements. A refined version of the prototype booklet was produced based on this feedback. A co-designed information booklet is available that addresses the uncertainties of men with AAA in surveillance. Future research should measure the impact of the information booklet on AAA-related anxiety. We set up a patient panel specifically for this study. We identified five men from different sources including asking the vascular clinicians on the team to invite patients to consider joining the panel and approaching existing health research studies patient panels to identify men who had AAA. One member of our team was the patient representative on the research committee for the NHS AAA Screening Programme in England. He attended all our patient panel meetings. The panel reviewed all the documents we used to invite men to different parts of the study, offered advice about recruitment, and gave feedback about the findings. They offered advice about the prototypes of the information booklet.

Intra-dural spinal tumours are a rare, yet diverse group of neoplasms, which may occur anywhere along the spinal neuroaxis. Their clinical presentations are typically slow and progressive in nature. Signs and symptoms are dictated by tumour location and size, and occur due to the sequalae of mass effect, oedema, ischaemia and subsequent metabolic dysfunction of neural tissue occurring secondary to compression of neural elements and neural vasculature. Back/neck pain and stiffness are the most common presenting complaint for patients presenting with intra-dural spinal tumours. Further symptoms are dependent on the location of the tumour. Lesions that compress or develop within the spinal cord are associated with upper motor neuron (myelopathic) signs and symptoms, whilst lesions compressing spinal nerves alone are associated with lower motor neuron (radicular) signs and symptoms. In some circumstances, a mixed picture of both upper and lower motor neuron symptoms may also be observed.

The clinical benefits of intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiation therapy (IMRT) for patients with oropharyngeal squamous cell carcinoma remain uncertain with respect to treatment-related effects on physical function and quality of life. We aimed to compare late functional, patient-reported, disease control, and survival outcomes between IMPT and IMRT. We did a phase 3 trial (TORPEdO) in 20 UK National Health Service hospitals. We randomly assigned (2:1) patients with locally advanced oropharyngeal squamous cell carcinoma to IMPT or IMRT (70 Gy in 33 fractions, for 6·5 weeks) with two cycles of high-dose cisplatin (100 mg/m2, every 3 weeks). Co-primary endpoints at 12 months were gastrostomy-tube dependence (use of feeding tube for nutrition) or severe weight loss (≥20% from baseline) and University of Washington quality of life (UW-QoL) mean physical composite score for saliva, taste, chewing, swallowing, speech and appearance. The study was registered with the ISRCTN registry, ISRCTN16424014; recruitment is complete and follow-up is ongoing. Between Feb 25, 2020, and June 13, 2023, we randomly assigned 205 patients (99 [48%] with T3 or T4 disease and 44 [22%] with bilateral neck lymph node involvement (N2[c]); 136 [66%] to IMPT and 69 [34%] to IMRT). 163 (80%) patients were male and 42 (20%) were female. Ethnicity data were self-reported by 177 (86%) patients; most were White British (167 [94%]). At 12 months, gastrostomy-tube dependence occurred in two (2%) of 119 patients in the IMPT group and in one (2%) of 59 patients in the IMRT group and severe weight loss occurred in 20 (18% [97·5% CI 11 to 28]) of 110 patients in the IMPT group and in three (6% [1 to 17]) of 53 patients in the IMRT group (combined odds ratio 2·80 [97·5% CI 0·75 to 10·4]; p=0·079). Mean UW-QoL physical composite scores at 12 months were 78·3 in the IMPT group versus 77·1 in the IMRT group (difference 1·3 [97·5% CI -3·7 to 6·2]; p=0·56). There were 14 serious adverse events in 12 patients (nine assessed as unrelated to the study treatment [four in the IMPT group and five in the IMRT group] and five study treatment-related [one IMPT vs four IMRT]); the most common events were acute kidney injury (five [36%]) and thromboembolism (four [29%]). There were no treatment-related deaths. At a median follow-up of 28·3 months (IQR 26·5 to 39·3), 24-month freedom from loco-regional recurrence rates were 94% (99% CI 86-98) in the IMPT group versus 97% (82-100) in the IMRT group (hazard ratio [HR] 2·6 [99% CI 0·3 to 20·3; 95% CI 0·5-12·4]; p=0·24), and overall survival rates were 95% (86 to 98) in the IMPT group versus 95% (81-99) in the IMRT group (HR 1·6 [99% CI 0·3 to 8·8; 95% CI 0·4 to 5·9; p=0·47). IMPT and IMRT had similar late physical quality of life scores, gastrostomy-tube dependence, local control, and overall survival. In health-care settings where IMPT is not used routinely for oropharyngeal squamous cell carcinoma, IMRT remains the standard of care. Cancer Research UK.

Abstract Background: Detection of circulating tumour DNA (ctDNA) in plasma predicts future recurrence in early breast cancer (EBC). Previous studies have relied on tumour-informed approaches with personalised assays. In this study, we performed orthogonal testing on plasma samples collected prospectively in the c-TRAK-TN study to compare a tissue-free assay with digital droplet PCR (ddPCR) for ctDNA analysis. Methods: c-TRAK-TN recruited 161 patients with early triple negative breast cancer (TNBC) deemed clinically high risk of relapse. Patients underwent ctDNA analysis by ddPCR starting within 4 weeks of completion of treatment and continuing every 3 months for up to 2 years. ddPCR tracked 1 or 2 patient specific variants as previously described. We further analysed 1062 timepoints from a total of 159 patients (median 7 per patient, range 1-11) using Guardant Reveal assay, a tissue-free approach that exploits differential methylation patterns in breast cancer compared with normal tissue. Results: Samples were successfully analysed from 95.3% (1012/1062) timepoints from 159 patients with the tissue-free Reveal assay. CtDNA was detected in 34.0% (54/159) of patients in at least 1 timepoint, with a median methylation tumour fraction of 0.266% (range 0.002 to 51.0%). Detection of ctDNA with the tumour agnostic assay strongly associated with future risk of relapse (HR 20.62, p&amp;lt;0.0001; logrank). Of patients who relapsed by 24 months follow up, 89.5% (34/38) of relapses were detected by prior ctDNA analysis. There were 159 patients available for comparison between ddPCR and the tissue-free assay (Reveal), in 1005 timepoints (median 7 per patient, range 1-11). Concordant test results were observed in 950/1005 timepoints with an overall agreement rate of 94.5%. In this cohort, 63.5% (101/159) of patients did not have ctDNA detected by either assay; 26.4% (42/159) had ctDNA detected by both assays and 10.1% (16/159) had discordant results. Of those detected, 44.8% (26/58) were detected by the tissue-free assay first and 6.9% (4/58) by ddPCR (p&amp;lt;0.0001, Fisher exact test). The median time from first detection of ctDNA to relapse for the tissue-free assay was 7.9 months (95% confidence interval (CI): 5.7-10.5 months) compared to ddPCR assay with 5.7 months (95% CI: 2.9-9.7 months) (HR = 0.6, p=0.0574; mixed effects cox model). Conclusion: Detection of ctDNA with a tissue-free assay anticipated relapse with high accuracy, in patients with early TNBC. The tissue-free assay frequently detected ctDNA at an earlier timepoint than ddPCR, trending towards a longer lead time from detection of ctDNA to relapse. Tissue-free approaches might offer simpler workflows for ctDNA analysis than tumour-informed approaches, and further assessment in clinical trials is warranted. Citation Format: N. Cunningham, R. J. Cutts, C. Swift, K. Dunne, M. Dewan, L. Kilburn, K. Goddard, P. Hall, C. Harper-Wynne, T. Hickish, I. Macpherson, A. Okines, A. Wardley, S. Waters, C. Palmieri, M. Winter, J. Bliss, D. Dustin, M. Ellis, I. Garcia- Murillas, N. C. Turner. Tissue-free circulating tumour DNA detection in patients with early triple negative breast cancer from the c-TRAK-TN trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF3-05.