Implementation of enhanced recovery pathways (ERPs) has resulted in improved patient-centred outcomes and decreased costs. However, there is a lack of high-level evidence for many ERP elements. We have designed a randomised, embedded, multifactorial, adaptive platform perioperative medicine (REMAP Periop) trial to evaluate the effectiveness of several perioperative therapies for patients undergoing complex abdominal surgery as part of an ERP. This trial will begin with two domains: postoperative nausea/vomiting (PONV) prophylaxis and regional/neuraxial analgesia. Patients enrolled in the trial will be randomised to arms within both domains, with the possibility of adding additional domains in the future.

In the PONV domain, patients are randomised to optimal versus supraoptimal prophylactic regimens. In the regional/neuraxial domain, patients are randomised to one of five different single-injection techniques/combination of techniques. The primary study endpoint is hospital-free days at 30 days, with additional domain-specific secondary endpoints of PONV incidence and postoperative opioid consumption. The efficacy of an intervention arm within a given domain will be evaluated at regular interim analyses using Bayesian statistical analysis. At the beginning of the trial, participants will have an equal probability of being allocated to any given intervention within a domain (ie, simple 1:1 randomisation), with response adaptive randomisation guiding changes to allocation ratios after interim analyses when applicable based on prespecified statistical triggers. Triggers met at interim analysis may also result in intervention dropping.

The core protocol and domain-specific appendices were approved by the University of Pittsburgh Institutional Review Board. A waiver of informed consent was obtained for this trial. Trial results will be announced to the public and healthcare providers once prespecified statistical triggers of interest are reached as described in the core protocol, and the most favourable interventions will then be implemented as a standardised institutional protocol.

NCT04606264.

To investigate the accumulation of adversities (duration of exposure to any, economic, psychosocial) across the lifecourse (birth to 63 years) on cognitive function in older age, and the mediating role of mental health.

National birth cohort study.

Great Britain.

5362 singleton births within marriage in England, Wales and Scotland born within 1 week of March 1946, of which 2131 completed at least 1 cognitive assessment.

Cognitive assessments included the Addenbrooke’s Cognitive Examination-III, as a measure of cognitive state, processing speed (timed-letter search task), and verbal memory (word learning task) at 69 years. Scores were standardised to the analytical sample. Mental health at 60–64 years was assessed using the 28-item General Health Questionnaire, with scores standardised to the analytical sample.

After adjusting for sex, increased duration of exposure to any adversity was associated with decreased performance on cognitive state (β=–0.39; 95% CI –0.59 to –0.20) and verbal memory (β=–0.45; 95% CI –0.63 to –0.27) at 69 years, although these effects were attenuated after adjusting for further covariates (childhood cognition and emotional problems, educational attainment). Analyses by type of adversity revealed stronger associations from economic adversity to verbal memory (β=–0.54; 95% CI –0.70 to –0.39), with a small effect remaining even after adjusting for all covariates (β=–0.18; 95% CI –0.32 to –0.03), and weaker associations from psychosocial adversity. Causal mediation analyses found that mental health mediated all associations between duration of exposure to adversity (any, economic, psychosocial) and cognitive function, with around 15% of the total effect of economic adversity on verbal memory attributable to mental health.

Improving mental health among older adults has the potential to reduce cognitive impairments, as well as mitigate against some of the effect of lifecourse accumulation of adversity on cognitive performance in older age.