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Assessing central nervous system contributions to accelerate musculoskeletal pain diagnosis and treatment (AsCent): protocol for a mixed-method, prospective observational study

Por: Clay · G. · Vanhegan · S. · Abbott · C. · Pearce · F. A. · Moffatt · F. · Bannister · K. · Graven-Nielsen · T. · Walsh · D. A. · Smith · S. L.
Introduction

Chronic musculoskeletal pain often extends beyond pathology alone. Augmented central pain processing is linked to pain severity, persistence and treatment outcomes. A practical clinical tool is needed to identify individuals likely to have persistent or worsening pain, likely due to augmented central pain mechanisms. Quantitative Sensory Testing (QST) offers mechanistic insight, while the Central Aspects of Pain (CAP) Questionnaire captures symptom profiles that potentially reflect central mechanisms. Combining a brief clinical QST protocol with CAP may support early risk stratification and guide personalised pain management.

Methods and analysis

This prospective observational study will recruit 250 individuals with inflammatory arthritis, osteoarthritis, chronic low back pain or fibromyalgia from existing cohorts, primary or secondary care. Participants will complete validated patient-reported outcomes at baseline, 6 and 12 weeks, with no additional intervention. The risk stratification tool completed at baseline will include clinical QST (Pressure Pain Threshold, Temporal Summation of Pain, Conditioned Pain Modulation), tender point count and the CAP questionnaire. Baseline laboratory versions of the clinical QST, plus Heat Pain Threshold, Offset Analgesia and the Central Sensitisation Inventory short form-9 questionnaire, will provide pain profiling to evaluate the predictive validity and psychometric properties of the tool. Data collection will include demographics, medical history, cognitive and neurological assessments and sleep quality via actigraphy (Actigraph wGT3X-BT). Interviews with patients and healthcare professionals will inform refinement, feasibility and acceptability of the tool.

Ethics and dissemination

Ethical approval was obtained from the Yorkshire & The Humber—South Yorkshire Research Ethics Committee (reference number: 24/YH/1062). Findings will be disseminated through peer-reviewed publications, conference presentations and patient-facing summaries and podcasts. The study aims to develop a clinically feasible tool to identify individuals at risk of persistent or worsening pain due to augmented central pain processing, enabling targeted treatment strategies.

Trial registration number

NCT06518278.

ProHealth: a co-designed online home-based healthy eating and exercise programme for men with prostate cancer treated with androgen deprivation therapy - a study protocol for a feasibility and preliminary efficacy randomised controlled trial

Por: Baguley · B. · Daly · R. · Livingston · P. · Rawstorn · J. · White · V. · Koorts · H. · Fraser · S. · Gardner · J. · Atkins · L. · Steer · B. · O · E. · Heneka · N. · Abbott · G. · Russell · G. · McNamara · G. · Kiss · N.
Background

Androgen deprivation therapy (ADT) improves survival in advanced prostate cancer but may lead to debilitating side effects, including sarcopenic obesity and a 10–45% increased risk of other comorbidities. Guidelines recommend exercise and nutrition interventions during ADT, but access to these services is often limited, and referral pathways are unclear. This study aims to evaluate the feasibility and preliminary efficacy of an online, home-based, multi-faceted, exercise, nutrition and education programme (ProHealth) for men with prostate cancer treated with ADT. ProHealth was co-designed with consumers and healthcare professionals to include (i) education on prostate cancer and treatment-related side effects and (ii) multimedia behaviour change resources to support individualised nutrition and exercise behaviour change.

Methods and analysis

This 12-week randomised controlled trial (target n=50) will include men treated with ADT for >3 months or who have completed ADT in the last 24 months, are overweight or obese and are not under the care of a dietitian or exercise professional. Participants will be randomised (1:1) to the ProHealth intervention or usual care. The intervention group will receive four consultations with an Accredited Practising Dietitian to promote a high protein and energy reduced diet, and five consultations with an Accredited Exercise Physiologist to follow a home-based progressive resistance training and aerobic exercise programme. The primary outcomes are feasibility (recruitment rate, retention, data completeness, reach, safety, consultation attendance and adherence, and usage of the ProHealth web platform), acceptability and satisfaction of the ProHealth intervention. Exploratory secondary outcomes will be assessed at baseline and 12 weeks and include changes in body weight and composition (total and appendicular fat-free mass, fat mass), quality of life (Functional Assessment of Cancer Therapy (FACT)—General, FACT-Prostate, FACT-Fatigue), physical function (30-second sit-to-stand), dietary intake (3-day food diary) and physical activity (7-day accelerometer). Linear regression models will estimate differences between the intervention and usual care group. Qualitative interviews on participant satisfaction will be transcribed verbatim for thematic analysis.

Ethics and dissemination

This study is approved by Deakin University Human Research Ethics Committee (DUHREC2024-038) and registered on Australian and New Zealand Clinical Trials Registry (ACTRN12624000874516). Findings will be disseminated through peer-reviewed journals, scientific meetings and other public forums.

Trial registration number

ACTRN12624000874516.

Personalising anal cancer radiotherapy dose (PLATO): protocol for a multicentre integrated platform trial

Por: Frood · R. · Gilbert · A. · Gilbert · D. · Abbott · N. L. · Richman · S. D. · Goh · V. · Rao · S. · Webster · J. · Smith · A. · Copeland · J. · Ruddock · S. P. · Berkman · L. · Muirhead · R. · Renehan · A. G. · Harrison · M. · Adams · R. · Hawkins · M. · Brown · S. · Sebag-Montefiore · D.
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

ISRCTN88455282.

Association of type 2 diabetes with reoperation, adverse events and mortality after hip and knee replacement: a Swedish register-based study including 109 938 hip and 80 897 knee replacements

Por: Vinblad · J. · Bülow · E. · Nyberg · F. · Eeg-Olofsson · K. · W-Dahl · A. · Limbäck · G. · Englund · M. · Abbott · A. · DellIsola · A. · Rolfson · O.
Objective

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.

Design

Observational study based on prospectively collected registry data analysed retrospectively.

Setting and participants

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.

Outcome measures

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.

Results

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).

Conclusion

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.

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