An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

CRD42025644244.

Low back pain (LBP) is the leading contributor to disability globally. It has a substantial impact on the lives of those who experience it, and places considerable economic burden on healthcare systems. Despite these impacts, and the consistency of guideline recommendations, many individuals do not receive recommended LBP management. Structural barriers to accessing timely, evidence-based care, as well as public uncertainty about where to seek appropriate management, can influence the care individuals receive. Telephone and digitally based helplines assist to overcome many traditional barriers to accessing care and offer a scalable platform to improve the delivery of guideline recommended management for LBP. However, uptake of such services can be limited without targeted promotion and patient-centred design. This project aims to codesign, implement and evaluate an upgraded component of an existing Australian helpline service, tailored for people with back pain and supported by a media awareness campaign. This protocol outlines the codesign process, implementation and planned evaluation of the helpline.

This protocol uses three complementary frameworks—an iterative codesign process, the Practical Robust Implementation Sustainability Model, and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework—to guide the codesign and development, implementation and evaluation of an upgraded helpline for people with LBP. The codesign process involves key stakeholders, including consumers and clinicians, to inform the development and implementation of both the upgraded helpline service and the media campaign to raise awareness and uptake of the helpline. Data sources will include a pre–post cohort of helpline service users, routinely collected service data (eg, monthly call rate) and health system data to evaluate the broader population level impact (eg, rates of emergency department presentations for LBP in the Australian region targeted by the media campaign). Implementation evaluation will include Reach, Effectiveness, Adoption, Implementation and Maintenance as well as internal and external environmental factors that influence the success of these outcome measures.

The project was approved by the University of Sydney’s Human Research Ethics Committee (HE001081). This project involves collaboration with consumers, clinicians and other stakeholders to interpret, translate and disseminate research findings to relevant audiences.

Peripheral arterial disease (PAD) commonly coexists with chronic kidney disease (CKD). Patients with symptomatic PAD often require endovascular revascularisation to relieve pain or salvage limbs. However, the iodinated intra-arterial contrast routinely used in these procedures is nephrotoxic, placing patients with CKD at increased risk of acute kidney injury (AKI) and long-term renal decline. Carbon dioxide (CO₂) delivered via automated injection is a potential alternative imaging contrast medium. This trial will evaluate whether using CO₂ instead of iodinated contrast reduces the risk of AKI and short-term renal function decline in this high-risk group.

This is a multicentre, open-label, prospective randomised controlled trial across six secondary-care National Health Service (NHS) vascular surgery centres. A total of 174 patients with PAD and CKD undergoing endovascular intervention will be randomised 1:1 to receive iodinated contrast (standard of care) or CO₂ via automated injector (Angiodroid). All perioperative care will follow local NHS protocols.

The primary outcome is log serum creatinine at 2, 30 and 90 days postprocedure. Key secondary outcomes include: incidence and severity of AKI within 48 hours postprocedure, major adverse kidney events (death, dialysis or >25% estimated glomerular filtration rate decline) by 90 days, inpatient length of stay, procedural pain, quality of life, procedural success, reinterventions, acceptability and feasibility (patient/practitioner questionnaires) of using CO₂, and cost-effectiveness (healthcare resource use analysis). A mixed-methods process evaluation will be undertaken with patients and clinicians.

The trial has been approved by an NHS ethical review committee (24/WA/0332) and patients have been involved in trial design. Findings will be disseminated to participants, clinicians and the wider public through patient groups, lay summaries, social media, conferences, peer-reviewed journals and NHS policy channels.

ISRCTN23564393.

The incidence of anal carcinoma is increasing, with the current gold standard treatment being chemoradiotherapy. There is currently a wide range in the radiotherapy dose used internationally which may lead to overtreatment of early-stage disease and potential undertreatment of locally advanced disease.

PLATO is an integrated umbrella trial protocol which consists of three trials focused on assessing risk-adapted use of adjuvant low-dose chemoradiotherapy in anal margin tumours (ACT3), reduced-dose chemoradiotherapy in early anal carcinoma (ACT4) and dose-escalated chemoradiotherapy in locally advanced anal carcinoma (ACT5), given with standard concurrent chemotherapy.

The primary endpoints of PLATO are locoregional failure (LRF)-free rate for ACT3 and ACT4 and LRF-free survival for ACT5. Secondary objectives include acute and late toxicities, colostomy-free survival and patient-reported outcome measures. ACT3 will recruit 90 participants: participants with removed anal tumours with margins ≤1 mm will receive lower dose chemoradiotherapy, while participants with anal tumours with margins >1 mm will be observed. ACT4 will recruit 162 participants, randomised on a 1:2 basis to receive either standard-dose intensity modulated radiotherapy (IMRT) in combination with chemotherapy or reduced-dose IMRT in combination with chemotherapy. ACT5 will recruit 459 participants, randomised on a 1:1:1 basis to receive either standard-dose IMRT in combination with chemotherapy, or one of two increased-dose experimental arms of IMRT with synchronous integrated boost in combination with chemotherapy.

This study has been approved by Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (ref: 16/YH/0157, IRAS: 204585), July 2016. Results will be disseminated via national and international conferences, peer-reviewed journal articles and social media. A plain English report will be shared with the study participants, patients’ organisations and media.

ISRCTN88455282.