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.

Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are globally prevalent chronic diseases that affect millions of individuals in ageing populations. Hip and knee replacements are well established and effective treatments in patients suffering from end-stage OA. Understanding how T2DM influences the outcomes of these surgeries is important for optimising patient care and improving surgical results. This study aimed to explore the association of T2DM with reoperation (regardless of the reason), adverse events (AEs) and mortality after primary hip and knee replacement surgery.

Observational study based on prospectively collected registry data analysed retrospectively.

Data from several Swedish national quality registers and health data registers were used to create a study database. 109 938 and 80 897 primary hip and knee replacements due to OA, performed between 2008 and 2019 (hip) and 2009 and 2018 (knee), were included in the study.

The risk of complications, such as reoperation, AEs and mortality, was investigated by estimating HRs using Cox regression, and OR using logistic regression, unadjusted and adjusted for confounding factors, such as patient characteristics, socioeconomic status and comorbidities, and mediators, such as surgical factors.

Adjusted multivariable Cox-regression analysis showed no T2DM-associated risk of reoperation after hip or knee replacement, adjusted HR 1.10 (95% CI 0.99 to 1.23) and 1.09 (95% CI 0.96 to 1.24), respectively, while T2DM was associated with increased risk of death after hip and knee replacement, adjusted HR 1.40 (95% CI 1.34 to 1.47) and 1.38 (95% CI 1.31 to 1.45). Adjusted logistic regression analysis showed T2DM-associated increase of reoperation within 90 days (OR 1.23 (95% CI 1.05 to 1.43)) and increased mortality within 90 days (OR 1.42 (95% CI 1.01 to 1.95)) following hip replacement; however, this was not the case after knee replacement, OR 1.08 (95% CI 0.85 to 1.36) for reoperation and OR 1.29 (95% CI 0.84 to 1.94) for mortality. Several factors closely linked with T2DM, such as body-mass index and comorbidities, were identified as important when assessing risk of reoperation and mortality. Regarding AEs within 30 and 90 days, very slight but not statistically significant T2DM-associated increases were seen after either hip replacement, OR 1.01 (95% CI 0.91 to 1.11) and 1.07 (95% CI 0.98 to 1.16) or after knee replacement, OR 1.05 (95% CI 0.93 to 1.17) and 1.08 (95% CI 0.98 to 1.19).

The observed risk of reoperation suggests that T2DM alone was not a strong justification to advise against hip or knee replacement in individuals with T2DM deemed eligible for joint replacement. The T2DM-associated increased mortality after hip and knee replacement is challenging to interpret, as T2DM itself without undergoing hip or knee replacement surgery is associated with increased mortality.