Wessam Abass

The phospholipase A2 receptor antibody (PLA2R-Ab) test is a valuable first-line diagnostic tool for primary membranous nephropathy (MN), helping to identify PLA2R-related MN and potentially eliminating the need for a kidney biopsy in some individuals. By reducing the reliance on biopsies, the test streamlines diagnosis and improves patient care. However, determining the optimal PLA2R measurement method and cut-off is critical to maximizing the benefits of the test and minimizing any harms. A systematic review and meta-analysis were performed to evaluate serum- and urine-based biomarkers for distinguishing between PLA2R-related MN and non-PLA2R MN. Searches were conducted in databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, International HTA Database and ClinicalTrials.gov. The methodology followed Cochrane-recommended guidelines for systematic reviews and meta-analyses, and the QUADAS-2 tool was utilized to assess the overall risk of bias. Ninety-one studies met the eligibility criteria for inclusion in the review. Of these, 38 studies reporting the accuracy of the PLA2R-Ab test using the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) method and 27 using the EUROIMMUN immunofluorescence (IF) method were suitable for meta-analysis. The pooled sensitivity and specificity of EUROIMMUN ELISA at a cut-off value of 20 RU/mL were 0.64 [95% confidence interval (CI) 0.56-0.72] and 94.7% (95% CI 90.5-97.1%), respectively. The pooled sensitivity and specificity of EUROIMMUN IF at a threshold of 1:10 was 0.69 (95% CI 0.637-0.739) and 0.98 (95% CI 0.931-0.994), respectively. Risk of bias was higher for studies evaluating the IF compared with ELISA test. We also explored whether the timing of the index test had an impact on the pooled diagnostic accuracy results; no significant differences were found. By evaluating the specificity and sensitivity of EUROIMMUN ELISA PLA2R-Ab and IF, we demonstrate that at ELISA levels ≥20 RU/mL, alongside thorough secondary screening, a kidney biopsy may be unnecessary. However, lower or negative levels still warrant a biopsy.

INTRODUCTION: Breast screening uptake remains low in parts of the UK, partly due to barriers including limited transport access. Offering free transport to screening appointments may help address this and improve uptake. This general practitioner (GP) cluster-randomised feasibility trial will assess whether offering free door-to-door transport alongside routine screening invitations increases attendance. METHODS AND ANALYSIS: Eight general practices in Yorkshire will be randomised to either the intervention (routine invitation plus information about booking free door-to-door transport) or control (routine invitation only) group. Around 8000 women due for routine breast screening will be included. Primary feasibility outcomes include GP recruitment and randomisation, intervention fidelity, proportion of women from the 10% most deprived areas, acceptability and data transfer processes. Secondary outcomes include understanding travel behaviour, cost-effectiveness and screening uptake. Data will be collected from routine National Health Service (NHS) screening records, data linkage with NHS England, travel surveys and qualitative interviews exploring experiences and acceptability. Patient and public involvement is embedded throughout with members contributing to advisory and oversight roles. ETHICS AND DISSEMINATION: The trial has received ethical approval from the London-Harrow Research Ethics Committee, Section 251 approval from the Confidentiality Advisory Group and other relevant regulatory bodies. The University of Hull is the study sponsor. Results will be disseminated through peer-reviewed journal publications, conference presentations and plain English summaries for participants and the public. Findings will inform the feasibility and design of a potential larger trial to improve breast screening uptake via transport support. TRIAL REGISTRATION NUMBER: ISRCTN17087898.