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Purpose Music therapy is an effective non-pharmacologic intervention that is cost-effective, easy to implement, and customize. It has been shown to significantly alleviate anxiety and improve patient satisfaction. In this study, we aimed to compare music therapy to a control (no music) group with respect to sedation requirements, anxiety levels, and patient satisfaction for patients undergoing total knee arthroplasty under spinal anesthesia. Methods In this randomized controlled study, we compared the effect of music therapy in patients ≥ 18 years old. Patients undergoing total knee arthroplasty were screened for the study to rule out any contraindications for spinal anesthesia. Patients were randomized in a 1:1 ratio for either the "music" or "control" group. Both groups were compared for sedation requirements, preoperative and postoperative anxiety levels, and patient satisfaction. Results Subjects in the music group had a statistically significant lower than average State-Trait Anxiety Inventory (STAI)-State baseline score as compared to the control group (music group 31.00 (standard deviation (SD) 1.44), control group 38.04 (SD 2.35); p = 0.01). Postoperative STAI-State-Trait Anxiety Inventory (STAI)-State scores for the music group were lower for the music group than the control group (music group 28.34 (SD 1.64), control group 32.21 (SD 1.56), p= 0.09). STAI-Trait scores were similar pre-operatively, but significantly less post-operatively in the music group (28.14 SD 1.0) as compared to the control group (34.71 SD 2.31); p = 0.01. Propofol dose per kilogram per surgical minute was similar between the two groups (music group 0.05, control group 0.06; p= 0.264). Patient satisfaction scores with their perioperative experience were higher in the music group (p= 0.009). Conclusions Music therapy may be offered as an alternative to traditional anxiolytics intra-operatively. However further studies are warranted to evaluate whether or not music therapy can decrease sedation and anxiolytic medications during surgery. The type and mode of delivery of music also need to be studied to better understand the impact of music therapy. Clinical trial registry: Clinicaltrials.gov # NCT03569397.
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The inflammatory cytokines IL-1beta and IL-6 have been shown to stimulate production of endothelin-1 (ET-1) by several cell types in vitro, but their effects on renal ET-1 production in vivo are not known. To test whether IL-1beta and IL-6 stimulate renal ET-1 production and release in vivo, urine was collected from male C57BL/6 mice over 24-h periods at baseline and on days 7 and 14 of a 14-day subcutaneous infusion of IL-1beta (10 ng/h), IL-6 (16 ng/h), or vehicle. By day 14, plasma ET-1 was significantly increased by IL-1beta infusion (1.7 +/- 0.1 vs. 0.8 +/- 0.1 pg/ml for vehicle, P < 0.001). Compared with vehicle infusion, IL-1beta infusion induced significant increases in urinary ET-1 excretion rate and urine flow but did not affect conscious mean arterial pressure (telemetry). IL-1beta infusion significantly increased renal cortical and medullary IL-1beta content (ELISA) and prepro-ET-1 mRNA expression (quantitative real-time PCR). In contrast, 14 days of IL-6 infusion had no significant effect on plasma ET-1 or urinary ET-1 excretion rate. To determine whether IL-1beta stimulates ET-1 release via activation of NF-kappaB, inner medullary collecting duct (IMCD-3) cells were incubated for 24 h with IL-1beta, and ET-1 release and NF-kappaB activation were measured (ELISA). IL-1beta activated NF-kappaB and increased ET-1 release in a concentration-dependent manner. The effect of IL-1beta on ET-1 release could be partially inhibited by pretreatment of IMCD-3 cells with an inhibitor of NF-kappaB activation (BAY 11-7082). These results indicate that IL-1beta stimulates renal and systemic ET-1 production in vivo, providing further evidence that ET-1 participates in inflammatory responses.