Patient and public involvement and engagement in the ASCEND PLUS trial: reflections from the design of a streamlined and decentralised clinical trial.

INTRODUCTION: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. AIM: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. METHODS: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. RESULTS: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. CONCLUSIONS: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial.

Protocol for an observational study investigating hormones triggering the onset of sustained lactation: the INSIGHT study.

INTRODUCTION: Lactation is a hormonally controlled process that promotes infant growth and neurodevelopment and reduces the long-term maternal risk of diabetes, cardiovascular disease and breast cancer. Hormones, such as prolactin and progesterone, mediate mammary development during pregnancy and are critical for initiating copious milk secretion within 24-72 hours post partum. However, the hormone concentrations mediating lactation onset are ill defined. METHODS AND ANALYSIS: The primary objective of the investigating hormones triggering the onset of sustained lactation study is to establish reference intervals for the circulating hormone concentrations initiating postpartum milk secretion. The study will also assess how maternal factors such as parity, pregnancy comorbidities and complications during labour and delivery, which are known to delay lactation, may affect hormone concentrations. This single-centre observational study will recruit up to 1068 pregnant women over a 3-year period. A baseline blood sample will be obtained at 36 weeks' gestation. Participants will be monitored during postpartum days 1-4. Lactation onset will be reported using a validated breast fullness scale. Blood samples will be collected before and after a breastfeed on up to two occasions per day during postpartum days 1-4. Colostrum, milk and spot urine samples will be obtained on a single occasion. Serum hormone reference intervals will be calculated as mean±1.96 SD, with 90% CIs determined for the upper and lower reference limits. Differences in hormone values between healthy breastfeeding women and those at risk of delayed onset of lactation will be assessed by repeated measures two-way analysis of variance or a mixed linear model. Correlations between serum hormone concentrations and milk composition and volume will provide insights into the endocrine regulation of milk synthesis. ETHICS AND DISSEMINATION: Approval for this study had been granted by the East of England-Cambridgeshire and Hertfordshire Research Ethics Committee (REC No. 20/EE/0172), by the Health Research Authority (HRA), and by the Oxford University Hospitals National Health Service Foundation Trust. The findings will be published in high-ranking journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN12667795.

Laparoscopic compared with open adrenalectomy for resection of pheochromocytoma: a review of 47 cases.

OBJECTIVE: We conducted a retrospective cohort study to determine whether laparoscopic adrenalectomy (LA) is a safe and effective therapy for the management of pheochromocytoma, as compared with open adrenalectomy (OA). METHODS: We collected pertinent data on 47 pheochromocytoma resections from 44 patient charts. Perioperative outcomes of 30 LAs were compared with 14 OAs. RESULTS: Median (and standard deviation [SD]) length of postoperative stay was shorter in the laparoscopic group (3.0, SD 3.3 d v. 6.0, SD 1.1 d; p < 0.05), and tumour size was smaller (3.9, SD 2.7 cm v. 5.0, SD 2.9 cm; p < 0.05). No statistically significant differences were found for operative time or rate of postoperative complications. There were no statistically significant between-group differences in intraoperative hypertensive episodes (systolic blood pressure > 180 and/or diastolic blood pressure > 90) or hypotensive episodes (systolic blood pressure < 100 and/or diastolic blood pressure < 60) or in the need for antihypertensive or vasopressive agents. There were no intraoperative complications related to extremes of blood pressure. There were no perioperative mortalities in this series, nor was there an increased risk of recurrent disease with the laparoscopic technique. CONCLUSION: LA is safe and effective for the management of pheochromocytoma.