ABSTRACT
Background: Patients who develop postoperative delirium (POD) have several clinical complications, such as increased morbidity, increased hospital stays, higher hospital costs, cognitive and functional impairment, and higher mortality. POD is a clinical condition preventable by standard non-pharmacological measures An intensive Occupational Therapy (OT) intervention has been shown to be highly effective in preventing delirium in critically ill medical patients, but it is unknown the effect in surgical patients. Thus, we designed a prospective clinical study with the aim to determine whether patients undergoing intervention by the OT team have a lower incidence of POD compared to the group treated only with standard measures. Methods: A multicenter, single-blind, randomized clinical trial was conducted between October 2018 and April 2021, in Santiago of Chile, at a university hospital and at a public hospital. Patients older than 75 years undergoing elective major surgery were eligible for the trial inclusion. Patients with cognitive impairment, severe communication disorder and cultural language limitation, delirium at admission or before surgery, and enrolled in another study were excluded. The intervention consisted of OT therapy twice a day plus standard internationally recommended non-pharmacological prevention intervention during 5 days after surgery. Our primary outcome was development of delirium and postoperative subsyndromal delirium. Results: In total 160 patients were studied. In the interventional group, treated with an intensive prevention by OT, nine patients (12.9%) developed delirium after surgery and in the control group four patients (5.5%) [p = 0.125, RR 2.34 CI 95 (0.75-7.27)]. Whereas subsyndromal POD was present in 38 patients in the control group (52.1%) and in 34 (48.6%) in the intervention group [p = 0.4, RR 0.93 CI95 (0.67-1.29)]. A post hoc analysis determined that the patient's comorbidity and cognitive status prior to hospitalization were the main risk factors to develop delirium after surgery. Discussion: Patients undergoing intervention by the OT team did not have a lower incidence of POD compared to the group treated only with standard non-pharmacological measures in adults older than 75 years who went for major surgery. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT03704090.
ABSTRACT
The complexity of the nervous system requires the coordination of multiple cellular processes during development. Among them, we find boundary formation, axon guidance, cell migration and cell segregation. Understanding how different cell populations such as glial cells, developing neurons and neural stem cells contribute to the formation of boundaries and morphogenesis in the nervous system is a critical question in neurobiology. Slit is an evolutionary conserved protein essential for the development of the nervous system. For signaling, Slit has to bind to its cognate receptor Robo, a single-pass transmembrane protein. Although the Slit/Robo signaling pathway is well known for its involvement in axon guidance, it has also been associated to boundary formation in the Drosophila visual system. In the optic lobe, Slit is expressed in glial cells, positioned at the boundaries between developing neuropils, and in neurons of the medulla ganglia. Although it has been assumed that glial cells provide Slit to the system, the contribution of the neuronal expression has not been tested. Here, we show that, contrary to what was previously thought, Slit protein provided by medulla neurons is also required for boundary formation and morphogenesis of the optic lobe. Furthermore, tissue specific rescue using modified versions of Slit demonstrates that this protein acts at long range and does not require processing by extracellular proteases. Our data shed new light on our understanding of the cellular mechanisms involved in Slit function in the fly visual system morphogenesis.
