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ABSTRACTBackground Chronic postsurgical pain (CPSP) may increase the risk of postoperative cognitive dysfunction (POCD) directly or by negatively impacting mobility. A comprehensive measure of satisfaction with surgery that accounts for ability to perform activities might be even more strongly associated with POCD. There might be complex mechanisms underlying the interplays between postoperative pain and cognition.Aims The primary objective is to explore whether CPSP at 6 months is associated with POCD (≥2-point decline in the Montreal Cognitive Assessment [MoCA] compared to preoperative) at 12 months. Secondary objectives are to explore the association between satisfaction with surgery and POCD, the role of pain medications (opioids) in the association between CPSP and POCD, the role of patient preoccupation/optimism and coping in determining the effect of pain on cognition, and the hypothesis of neurogenesis interference as an underlying mechanism.Methods We will prospectively recruit ≥100 patients ≥50 years old undergoing elective total knee/hip arthroplasty. Sociodemographic characteristics, comorbidities, frailty, pain, and pain medications will be assessed preoperatively. The Somatic Preoccupation and Coping questionnaire will be administered preoperatively and 4 to 6 weeks postoperative. Pain and the Self-Administered Patient Satisfaction Scale will be measured at 3 and 6 months. MoCA and neuropsychological tests will be administered at baseline, 4 to 6 weeks, and 6 and 12 months. Blood will be longitudinally collected for biomarker analysis.Progress Forty-six participants have been enrolled in the study so far.Conclusion ArthroCaP will provide preliminary data on the association of CPSP and patient satisfaction with POCD and underlying mechanisms. It will inform larger confirmatory and interventional studies to enhance the benefits of surgery.

ABSTRACTBackground Total knee arthroplasties are the second most common surgery in Canada. Most patients recover well, but 20% or more still suffer from persistent pain and opioid use. Though opioids are an important part of perioperative pain management, their potential for long-term adverse effects is well recognized. Limiting opioids may be insufficient to overcome the issue of opioid overuse. Pain and opioid use are highly linked, so an effective alternative needs to address both issues.Objectives The principal objective of this pilot trial is to assess the feasibility. The clinical objectives are to determine the effects of a multicomponent care pathway on opioid-free pain control, persisting pain and opioid use, functional knee outcomes, quality of life, and return to function.Methods We will include adult patients scheduled for primary elective total knee arthroplasty. Patients in the intervention group will undergo a multicomponent intervention pathway that will be facilitated by an intervention coordinator linking each patient and their surgical/ perioperative team. The interventional pathway will include (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation using cognitive behavioral skills, (3) personalized postdischarge analgesic prescriptions, and (4) continued support for pain control and recovery up to 8 weeks. Patients in the control group will receive the usual care at their institution.Discussion The overarching goal is to implement and evaluate a coordinated approach to clinical care to improve pain control and reduce harms, with an emphasis on patient-centered care and shared decision making.Trial Registration Number: NCT04968132 (informed consent/ research ethics board statement).

The earliest post-launch training activities around the Principlesaimed mainly to raise awareness and generate acceptancefrom government, NGO, UN and international actors. Inrecent years, training has moved beyond awareness raisingto applying the Principles and setting global standards.

In order to determine whether kidney hypertrophy secondary to unilateral nephrectomy was an appropriate model to study cytoplasmic androgen receptor modulation, this receptor was measured three weeks after surgery in intact or castrated animals. Our results demonstrate that the process of kidney hypertrophy is not accompanied by a proportional elevation of the number of androgen receptors and that these receptors are not significantly influenced by the gonadal activity in the rat.

In the course of our studies on the fate of cytoplasmic receptors for androgens in various target organs, such a receptor has been partially characterized in rat kidney cytosol: the high affinity constant, the specificity for testosterone and the formation of a hormone-receptor complex with a 8-10S sedimentation coefficient on sucrose density gradient led us to estimate that this macromolecule was similar to the rat prostate androgen receptor. This receptor is partially occupied by circulating androgens because the number of binding sites increases following castration or hypophysectomy. Constant levels of receptors have been recorded for several months in absence of testosterone. The age and the sex of animals, as well as the functional state of thyroid gland, did not affect the number of binding sites. These receptor characteristics may explain the slight renotrophic action of androgens in rat kidney.