BACKGROUND: Music therapy has been used as a complementary intervention to provide synergistic analgesia for various procedures.
OBJECTIVE: To evaluate the effects of natural sound therapy on pain intensity and agitation scores in intubated adult Chinese patients who received endotracheal suctioning in a critical care unit.
METHODS: A prospective, real-world, randomized, double-blind, controlled study was conducted from July 2021 through February 2022 among intubated surgical intensive care unit patients in a Chinese hospital. Patients were randomly assigned to a control group receiving conventional treatment or an intervention group receiving natural sound therapy plus conventional treatment (50 patients in each group). Patients\' pain intensity and agitation levels were analyzed before, during, immediately after, 5 minutes after, and 15 minutes after completion of endotracheal suctioning. Pain intensity was assessed with the Critical-Care Pain Observation Tool (CPOT); agitation was assessed with the Richmond Agitation-Sedation Scale (RASS).
RESULTS: According to CPOT scores, patients in the intervention group had significant relief of pain intensity during, immediately after, and 5 minutes after endotracheal suctioning compared with patients in the control group (all P < .001). The RASS scores showed that agitation levels were significant lower in the intervention group than in the control group during (P = .002) and immediately after (P < .001) endotracheal suctioning.
CONCLUSIONS: In this real-world study, natural sound therapy was part of a holistic bundle of interventions used to reduce pain and agitation in surgical intensive care unit patients during endotracheal suctioning.

OBJECTIVE: In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only.
METHODS: Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24.
RESULTS: Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52.
CONCLUSIONS: Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.

BACKGROUND: To investigate whether intravenous administration of tranexamic acid (TXA) prior to arthroscopic rotator cuff repair improves operative blood loss, postoperative fibrinolytic index, inflammatory response, and postoperative pain.
METHODS: This was a prospective, double-blind, randomized controlled study. From January 2023 to February 2024, 64 patients who required arthroscopic rotator cuff repair were included and divided into tranexamic acid group (T group) group and control group (C group) according to the random number table method. In T group, 1000 mg TXA was administered intravenously 10 minutes before surgery, and an equivalent dose of normal saline was administered intravenously 10 minutes before surgery in C group. Intraoperative bleeding, postoperative fibrinolytic indexes, inflammatory indexes, pain scores, and occurrence of adverse effects were compared between the 2 groups.
RESULTS: Intraoperative bleeding in T group was lower than that in C group (P < .05); D-D and FDP in T group were significantly lower than those in C group (P < .05); postoperative TNF-α and IL-6 in 2 groups was higher than that before operation and T group was lower than C group (P < .05); The pain scores of the 2 groups after operation were lower than those before operation (P < .05), and there was no difference between the 2 groups (P > .05).
UNASSIGNED: TXA is able to reduce blood loss and inflammatory reactions, modulate fibrinolytic function, and promote postoperative recovery in patients undergoing arthroscopic rotator cuff repair, with no elevated risk of complications.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure.
METHODS: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively.
RESULTS: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001).
CONCLUSIONS: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

BACKGROUND: Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem.
METHODS: This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score.
CONCLUSIONS: Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function.
BACKGROUND: Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

BACKGROUND: Brown seaweed is promising for the treatment of type 2 diabetes mellitus (T2DM). Its bioactive constituents can positively affect plasma glucose homeostasis in healthy humans. We investigated the effect of the brown seaweeds Sargassum (S.) fusiforme and Fucus (F.) vesiculosus in their natural form on glucose regulation in patients with T2DM.
METHODS: We conducted a randomized, double-blind, placebo-controlled pilot trial. Thirty-six participants with T2DM received, on a daily basis, either 5 g of dried S. fusiforme, 5 g of dried F. vesiculosus, or 0.5 g of dried Porphyra (control) for 5 weeks, alongside regular treatment. The primary outcome was the between-group difference in the change in weekly average blood glucose levels (continuous glucose monitoring). The secondary outcomes were the changes in anthropometrics, plasma lipid levels, and dietary intake. The data were analyzed using a linear mixed-effects model.
RESULTS: The change in weekly average glucose levels was 8.2 ± 2.1 to 9.0 ± 0.7 mmol/L (p = 0.2) in the S. fusiforme group (n = 12) and 10.1 ± 3.3 to 9.2 ± 0.7 mmol/L (p = 0.9) in the F. vesiculosus group (n = 10). The between-group difference was non-significant. Similarly, no between-group differences were observed for the changes in the secondary outcomes.
CONCLUSIONS: A daily intake of 5 g of fresh, dried S. fusiforme or F. vesiculosus alongside regular treatment had no differential effect on weekly average blood glucose levels in T2DM.

BACKGROUND: The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points.
METHODS: This RCT will recruit 126 patients with MDD who will be randomised using stratified permuted block randomisation into three groups, which are the combined e-ACT programme, ACT-only and TAU control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT-only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the pre-intervention assessment (t0), assessment immediately after completion of the intervention at 8 weeks (t1) and assessment at 24 weeks after completion of the intervention (t2). During each assessment, the primary outcome to be assessed includes the severity of depression symptoms, while the secondary outcomes to be assessed are the severity of anxiety symptoms, experiential avoidance, QoL and depression biomarkers.
BACKGROUND: Approval of this study was obtained from the Human Research Ethics Committee of Universiti Sains Malaysia (USM/JEPeM/PP/23050420). The findings of the study will be published in academic peer-reviewed journals.
BACKGROUND: NCT05812001 (ClinicalTrials.gov). Registered on 12 April 2023.

OBJECTIVE: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).
METHODS: Multicentre, double blind, randomised, placebo controlled trial.
METHODS: 244 hospitals in China between 11 August 2022 and 13 April 2023.
METHODS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled.
METHODS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days.
METHODS: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat.
RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83).
CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L.
BACKGROUND: ClinicalTrials.gov, NCT05439356.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a prevalent and life-threatening liver disease with high short-term mortality. Although recent clinical trials on the use of mesenchymal stem cells (MSCs) for ACLF treatment have shown promising results, multicentre randomised controlled phase II clinical trials remain uncommon. The primary aim of this trial is to assess the safety and efficacy of different MSCs treatment courses for ACLF.
METHODS: This is a multicentre, double-blind, two-stage, randomised and placebo-controlled clinical trial. In the first stage, 150 patients with ACLF will be enrolled and randomly assigned to either a control group (50 cases) or an MSCs treatment group (100 cases). They will receive either a placebo or umbilical cord-derived MSCs (UC-MSCs) treatment three times (at weeks 0, 1 and 2). In the second stage, 28 days after the first UC-MSCs infusion, surviving patients in the MSCs treatment group will be further randomly divided into MSCs-short and MSCs-prolonged groups at a 1:1 ratio. They will receive two additional rounds of placebo or UC-MSCs treatment at weeks 4 and 5. The primary endpoints are the transplant-free survival rate and the incidence of treatment-related adverse events. Secondary endpoints include international normalised ratio, total bilirubin, serum albumin, blood urea nitrogen, model for end-stage liver disease score and Child-Turcotte-Pugh score.
BACKGROUND: Ethical approval of this study has been obtained from the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-3-19-1). All results of the study will be submitted to international journals and international conferences for publication on completion of the study.
BACKGROUND: NCT05985863.

OBJECTIVE: To assess the efficacy of Phyllanthus emblica extract in alleviating halitosis and reducing the inflammatory response to halitosis-related bacteria.
METHODS: This investigation, using Phyllanthus emblica fruit extract (PE), involved four aspects. First, we evaluated the effect on growth and aggregation of halitosis-related bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, and Solobacterium moorei, using a microdilution assay and scanning electron microscopy. Second, volatile sulfur compound (VSC) levels were measured on individuals with halitosis in randomized short-term (26 participants) and double-blind randomized long-term trials (18 participants in each group) after rinsing with PE for 3, 6, and 12 h, and 28 days. Third, we analyzed pro-inflammatory cytokine expression in TR146 cells using quantitative real-time PCR and enzyme-linked immunosorbent assays. Lastly, we assessed pro-inflammatory cytokine secretion and Toll-like receptor (TLR) 2 mRNA expression via the same experimental methods in a three-dimensional oral mucosal epithelial model (3D OMEM).
RESULTS: PE extract dose-dependently inhibited the growth of F. nucleatum (50% inhibition concentration [IC50]=0.079%), P. gingivalis (IC50=0.65%), and S. moorei (IC50=0.07%) and effectively prevented bacterial aggregation. Furthermore, VSC contents decreased significantly at 3, 6, and 12 h after rinsing with 5% PE compared with those in the control. Long-term use of mouthwash containing 5% PE for 28 days led to a significant decrease in VSC contents. PE attenuated the F. nucleatum- or P. gingivalis-stimulated mRNA expression and protein release of interleukin (IL)-6 and IL-8 in TR146 cells. It also suppressed IL-8 and prostaglandin E2 secretion and TLR2 mRNA expression in F. nucleatum-induced OMEMs.
CONCLUSIONS: Our findings support the use of PE in oral care products to alleviate halitosis and it may reduce inflammation.