Detecting cancer earlier improves treatment options and long-term survival. A multicancer early detection test that reliably picks up early-stage cancer would potentially save lives and reduce the cost of treating cancer. One promising candidate is the Enlighten test, which applies machine learning to plasma amino acid concentrations to detect cancer. In a cohort of 77 patients recently diagnosed with breast, colorectal, pancreatic or prostate cancer, 60 (78%) were detected by the test (sensitivity), with no false positives in 20 healthy controls. The MODERNISED study will further develop the Enlighten test to detect 10 different cancers by adding bladder, lung, melanoma, oesophageal, ovarian and renal cancer to the test.

MODERNISED (ISRCTN17299125) is a multicentre prospective, non-interventional, case–control study. We aim to recruit 1000 adult participants with a recent cancer diagnosis, 250 adult participants with symptoms of cancer where a cancer diagnosis was ruled out by the National Health Service (NHS) standard of care and 100 healthy adult volunteers. Cancer tissue of origin (ToO) will include bladder, breast, colorectal, lung, melanoma, oesophageal, ovarian, pancreatic, prostate and renal. Participants in the two non-cancer cohorts who are later diagnosed with cancer will be moved to the cancer cases cohort. The primary aim is to train and validate a machine learning algorithm to detect cancer, which will be evaluated by AUROC. Secondary aims include training and validating an algorithm to predict ToO and stage of cancer, exploring differences in performance by demographics and estimating how sensitivity varies across specificity cut-offs of 95%, 99% and 99.9%. These results will provide a statistically powered estimate of how well the Enlighten test can discriminate between individuals with and without cancer, which can then be validated for clinical use in further research.

This study is sponsored by University Hospital Southampton NHS Foundation Trust and has been approved by the Health Research Authority and Health and Care Research West Midlands (24/WM/0234). Results will be presented at scientific meetings and published in international peer-reviewed journals. Lay summaries of study progress and findings will be published on the Southampton Clinical Trial Unit’s website.

ISRCTN17299125.

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.

Difficulty with walking can lead to reduced quality of life for people with Parkinson’s disease (pwPD); improving walking is considered a treatment priority. Drug therapies can control PD symptoms; however, pwPD often still experience mobility problems.

Functional electrical stimulation (FES) induces movement in weak muscles via external electrical stimulation. FES is used in stroke and multiple sclerosis patients to correct dropped foot by stimulating the common peroneal nerve and is associated with improved quality of life and mobility. The randomised feasibility study preceding this definitive study showed that daily FES can produce a clinically meaningful improvement in walking speed in pwPD; this was sustained 4 weeks after FES was withdrawn. STEPS II is the first definitive randomised controlled trial, with blinded outcome assessment, aiming to determine the efficacy of FES in pwPD.

STEPS II is a two-group, parallel, assessor-blinded, superiority randomised controlled trial with an internal pilot, designed to compare FES plus usual care versus usual care alone. 234 participants will be randomised across eight UK sites. Telephone pre-screening and face-to-face screening will determine eligibility. The intervention group will attend four unblinded FES visits to receive the device and assess walking with and without FES. All participants have blinded assessments at baseline and weeks 2, 6, 18 and 22. The primary objective is to compare whole body bradykinesia at 18 weeks post-baseline via changes in 10m walking speed. Secondary objectives will assess the wider effects of FES on Parkinsonian gait and quality of life. An embedded qualitative component will explore wider experiences of FES.

This study received ethical approval from the Yorkshire and The Humber-Sheffield Research Ethics Committee (reference 23/YH/0193). A Data Monitoring Committee and Trial Steering Committee will provide independent oversight. Dissemination will be via publications, conferences and social media. FES intervention and training materials will be made open access.

ISRCTN13120555.