Multipoint pacing is associated with improved prognosis and cardiac resynchronization therapy response. MORE-CRT MPP randomized study secondary analyses.

BACKGROUND AND AIMS: Cardiac resynchronization therapy (CRT) via biventricular (BIV) pacing is indicated in patients with heart failure (HF), reduced ejection fraction and prolonged QRS duration. Quadripolar leads and MultiPoint Pacing (MPP) allow multiple left ventricle (LV) sites pacing. We aimed to assess clinical benefit of MPP in patients who do not respond to standard BIV pacing. METHODS: Overall 3724 patients were treated with standard BIV pacing. After 6 months, 1639 patients were considered as CRT non-responders (echo-measured relative reduction in LV end-systolic volume (LVESV) < 15%) and randomized to MPP or BIV. RESULTS: We analysed 593 randomized patients (291 MPP, 302 BIV), who had BIV pacing >97% of time before randomization and complete 12-months clinical and echocardiographic data. The endpoint, composed by freedom from cardiac death and HF hospitalizations, and by LVESV relative reduction ≥15% between randomization and 12 months, occurred more frequently in MPP (96/291 (33.0%)) vs. BIV (71/302 (23.5%), p = 0.0103), also confirmed at multivariate analysis (hazard ratio = 1.55, 95% confidence interval = 1.02-2.34, p = 0.0402 vs. BIV). HF hospitalizations occurred less frequently in MPP (14/291 (4.81%)) vs. BIV (29/302 (9.60%), incidence rate ratio = 50%, p = 0.0245). Selecting patients with large (>30 ms) dispersion of interventricular electrical delay among the 4 LV lead dipoles, reverse remodeling was more frequent in MPP (18/51 (35.3%)) vs. BIV (11/62 (17.7%), p = 0.0335). CONCLUSION: In patients who do not respond to standard CRT, despite high BIV pacing percentage, MPP is associated with lower occurrence of HF hospitalizations and higher probability of reverse LV remodeling, compared with BIV pacing.

The Effect of Virtual Reality Distraction and Fatigue Training on Anxiety and Fatigue Levels in Children with Cancer: A Randomized Controlled Study.

OBJECTIVES: This randomized controlled trial evaluated the effect of virtual reality (VR) distraction and fatigue training on anxiety and fatigue in children with cancer. METHODS: The sample of this parallel design randomized controlled trial consisted of 41 children aged 7 to 16 who were receiving chemotherapy treatment in the pediatric hematology and oncology wards of a university hospital. Data was collected with the Child Anxiety Scale-State, Child Fatigue Scale-24-Hours, and Visual Fatigue Scale in both groups before and during the first three days of chemotherapy treatment. All children admitted to the clinic during chemotherapy received fatigue education. On the first, second, and third days of chemotherapy treatment, children in the study group underwent a 15-minute VR distraction intervention following stratified randomization. Repeated measures analysis of variance was used to compare scale scores by group, time, and group-time interaction. RESULTS: Of the patients, 63.4% were male, and 39% had neuroblastoma. There was no difference between the groups in terms of diagnosis, age, duration of diagnosis, chemotherapy, or hemoglobin levels. A statistically significant difference was found between the mean scores of the anxiety and fatigue scores in the intervention and control groups in terms of group, time, and group-time interaction. CONCLUSION: Applying VR distraction on the first, second, and third days of chemotherapy treatment was found to be useful in lowering anxiety and fatigue levels in addition to fatigue training. IMPLICATIONS FOR NURSING PRACTICE: Virtual reality distraction is an effective method for reducing anxiety and fatigue in this population.

The influence of sleep education supported and unsupported with social media reminders on the sleep quality in adolescents aged 14-18: a three-center, parallel-arm, randomized controlled study.

PURPOSE: Poor sleep quality is a global health problem for adolescent. The aim of this study was to examine how sleep education, with or without social media reminders, affects sleep quality in adolescents aged 14 to 18. METHODS: The study was a three-center, parallel-arm, randomized controlled study, recruiting participants from September 9, 2019, to January 6, 2020. Adolescents with poor sleep quality and sleepiness, using smartphones apps and internet browser, without chronic diseases, and obesity, and without mental problems were included in the study. Primary outcomes were sleep quality, sleepiness, sleep hygiene, and sleep parameters at week 5 as measured by subjective report scales and actigraphy. Sleep quality was measured by the Pittsburgh Sleep Quality Index (Poor sleep quality = PSQI > 5), sleepiness by the Cleveland Adolescent Sleepiness Questionnaire (CASQ > 16), and sleep hygiene developed by the researchers in the literature of Adolescent Sleep Habits Form. RESULTS: A total of 55 participants (mean [SD] age, 15.64 [1.22] years) participated. PSQI and CASQ scores of adolescents in sleep education that were not supported by social media reminders decreased compared to the baseline (p = 0.01, p = 0.02). Adolescent PSQI score in sleep education supported by social media reminders decreased from baseline, their sleep hygiene score increased (p = 0.02). There were no significant differences between the groups in terms of sleep parameters (total sleep duration, deep and light sleep levels, nighttime sleeping, and morning wake-up times) (p > 0.05). CONCLUSION: This study suggests that sleep education, supported by reminders via social media, can be used to improve the quality of sleep of adolescents. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05071989.

Feracrylum-An Unexplored Aspect of Local Drug Delivery in Treating Chronic Periodontitis: An Original Research.

Background: Targeted and efficient therapy strategies are necessary to address the global threat that chronic periodontitis poses to oral health. Antibiotic resistance is one drawback of traditional methods like scaling and root planing in conjunction with systemic antibiotics. Techniques: A study with 120 people who had been diagnosed with chronic periodontitis was done using randomized controlled trials. The subjects were grouped as the Feracrylum group and the placebo group. Clinical measures were measured at baseline and again after 12 weeks. These parameters included gingival index, clinical attachment level, and "probing pocket depth (PD)." A 3% solution was locally applied to periodontal pockets in the Feracrylum group, whereas a saline solution was given to the placebo group. Findings: As compared with other cohorts, the Feracrylum group showed a substantial improvement in clinical attachment level and a significant decrease in PD (P < 0.05). Although not statistically significant, the gingival index reduction in the Feracrylum group showed a tendency in the direction of better gingival health. Conclusion: In summary, feracrylum has the potential as a localized medication delivery adjunct for chronic periodontitis, leading to positive clinical results. Larger sample numbers and longer follow-up times are required for future studies to confirm these results and maximize the use of feracrylum in periodontal treatment.

The impact of group cognitive behavioral psychotherapy on disease severity and psychosocial functioning in patients with inflammatory bowel disease: a randomized controlled study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) often report symptoms of anxiety and depression as well as impaired quality of life (QoL). To date, there are few studies on the effect of psychotherapy on psychological functioning and clinical outcome in patients with IBD. The aim of this prospective, randomized, controlled study was to investigate the effect of a brief psychotherapeutic intervention on psychological distress, QoL, sexual functioning, and inflammation and disease activity indices in patients with IBD. METHODS: Participants were randomized to receive either group cognitive behavioral therapy or treatment as usual (controls) and were assessed at baseline and after six months using psychometric instruments to assess psychological distress, QoL, and sexual functioning. In addition, laboratory measurements, including levels of C-reactive protein (CRP), cytokines and calprotectin, and calculations of disease activity indices were performed during the two study periods. RESULTS: 80 participants took part in the study. Patients who received psychotherapy reported a significant decrease in anxiety and depression symptoms, a significant improvement in physical functioning, general health, vitality, social functioning and mental health, a decrease in physical pain and a decrease in role limitations caused by emotional problems. CRP levels and the Crohn's disease activity index (CDAI) also decreased significantly at follow-up compared to controls. CONCLUSIONS: Group cognitive behavioral therapy is proving to be an important component of holistic care for IBD patients, as it can significantly improve not only patients' psychosocial functioning but also their clinical course by inhibiting inflammation and reducing disease activity.

Comparative Evaluation of Clinical Outcome Including Neurosensory Deficit and Pain Score Variables Using Rigid Internal Fixation with Three-Dimensional Miniplate Internal Fixation in Simultaneous Angle and Contralateral Body/Parasymphysis Fractures of the Mandible: A Prospective, Randomized Controlled Study.

Purpose There have been numerous advancements in the strategies used for treating mandibular fractures in the present times, while open reduction and internal fixation is still accepted as the most preferred treatment option for such fractures despite numerous drawbacks. The aim of the present prospective, randomized controlled study was to evaluate the clinical outcome including neurosensory deficit and pain score variables in mandibular fractures that were treated using rigid internal fixation with three-dimensional (3D) miniplate internal fixation. Materials and Methods For the present study, a total of 20 patients of either sex in an age range of 18 to 55 years with simultaneous angle and contralateral body/parasymphysis fractures of the mandible were included, while the clinical outcome was compared in relation to the two groups wherein different treatment options were used including using rigid internal fixation in one as against 3D miniplate internal fixation in the other. Results Pairwise comparison of pain scores in Group I and Group II patients by the Mann-Whitney U-test at different time zones revealed the results to be statistically significant for all pairs except when the findings were compared between 1 month and 3 months after the procedure in Group II patients. Also, significant recovery was observed in both Group I and II patients during healing when assessed preoperatively to 1 month and then 3 months after the procedure with the results being statistically highly significant in case of the variations observed in relation to the neurosensory deficit observed at different time zones for both Group I and II patients ( p = 0.0001). Conclusion Based on the results obtained, it can be concluded that 3D miniplate-led osteosynthesis was found comparable to the osteosynthesis accomplished using reconstruction plates during fixation of unfavorable body/parasymphysis fractures of mandible in study, providing optimal stability, while satisfactorily meeting the biomechanical requirements for occlusal loading, and an early return to normal function.

A Comparison of Subarachnoid Block Characteristics Following Co-administration of Fentanyl Premixed With Hyperbaric Bupivacaine Versus Antecedent or Succedent to Hyperbaric Bupivacaine: A Randomized Controlled Study.

Background Adjuvants are often used during subarachnoid block to enhance and prolong the analgesia and decrease the adverse effects of high doses of local anesthetic agents. Intrathecal fentanyl premixed with hyperbaric bupivacaine has been used in spinal anesthesia and compared with the sequential use of these drugs in separate syringes. However, given the paucity of literature, we conducted this study where premixed antecedent and succedent administration of intrathecal fentanyl with hyperbaric bupivacaine were compared in terms of flow dynamics, block characteristics, and hemodynamic alterations. Methodology This prospective, randomized, triple-blinded comparative study was conducted among 160 patients who were randomly allocated into four groups. Group A (n = 40) (control) received 3.0 mL (15 mg) of 0.5% hyperbaric bupivacaine and 0.5 mL of normal saline via a 5.0 mL syringe. Group B (n = 40) received 3.0 mL (15 mg) of 0.5% hyperbaric bupivacaine and 0.5 mL (25 µg) of fentanyl premixed via a single 5.0 mL syringe. Group C (n = 40) received 0.5 mL (25 µg) of fentanyl via a 1.0 mL syringe followed by 3.0 mL (15 mg) of 0.5% hyperbaric bupivacaine via a 5.0 mL syringe. Group D (n = 40) received 3.0 mL (15 mg) of 0.5% hyperbaric bupivacaine via a 5.0 mL syringe followed by 0.5 mL (25 µg) of fentanyl via a 1.0 mL syringe. The onset and regression of sensory and motor blockade, hemodynamic parameters, time to first rescue analgesia, and adverse events were observed. Data analysis was done using SPSS version 17.0 (SPSS Statistics Inc., Chicago, IL, USA). Results The mean time taken for the onset of sensory and motor blockade was least in Group D followed by Group C. Duration of sensory and motor blockade was prolonged in Group D. Patients in Group A experienced more hypotension than Groups B, C, and D. Requirement of rescue analgesia was delayed in Groups C and D. Conclusions Administering 25 µg (0.5 mL) of Fentanyl separately after 15 mg (3.0 mL) of 0.5% hyperbaric bupivacaine results in early onset and prolonged duration of sensory and motor blockade, intraoperative hemodynamic stability, the delayed requirement of rescue analgesia postoperatively, and fewer side effects compared to its co-administration as a premixed solution or antecedent to hyperbaric bupivacaine.

Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. OBJECTIVE: To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. METHOD: In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. RESULTS: Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. CONCLUSION: These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Efficacy and Safety of Dexmedetomidine in the Prone Position in Elderly Patients with Pneumonia: A Prospective, Double-Blind, Randomized Controlled Study.

PURPOSE: We aimed to identify a safe and effective method to assist older adults with pneumonia in tolerating the prone position for a longer duration. METHODS: This was a randomized, controlled, double-blinded study performed at the Shanghai Fourth People's Hospital. Eighty patients with pneumonia aged ≥ 65 years were included. The patients were able to spontaneous breath in the prone position and were administered intravenous dexmedetomidine or an isotonic sodium chloride solution. The cumulative daily durations of prone positioning for all patients in the two groups were recorded. The primary outcome was the percentage of patients who completed ≥ 9 h/day in the prone position. The secondary outcomes included the incidence of complications in the prone position and patient outcomes. RESULTS: Eighty patients were included (average age: 79.6 ± 8.9 years). The percentage of patients who completed ≥ 9 h/day in the prone position was significantly higher in the dexmedetomidine group than in the placebo group (P = 0.011). The percentage of patients who completed ≥ 12 h/day in the prone position was also significantly greater in the dexmedetomidine group than in the placebo group (P = 0.008). There were no significant differences in other variables between the two groups. CONCLUSIONS: The results of this study demonstrate that intravenous dexmedetomidine injection can significantly prolong the duration of spontaneous breathing in the prone position in elderly pneumonia patients without obvious adverse events. We provide a safe and effective method to help patients with pneumonia, especially those with delirium or cognitive impairment, who cannot tolerate the length of time needed for spontaneous breathing in the prone position to be effective. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Center (registration number: ChiCRT2300067383) on 2023-01-05.

A randomized controlled trial analyzing nonthermal atmospheric plasma for the treatment of verruca vulgaris in pediatric patients.

BACKGROUND: Verruca vulgaris (VV) is a common viral disease in children. Treatment options are often not well tolerated in children due to pain or adverse effect risk. Nonthermal atmospheric plasma (NTAP), which generates reactive oxygen/nitrogen species, is well tolerated and without adverse effects. OBJECTIVE: Determine efficacy of NTAP as compared to standard of care (SOC) therapy for VV in children. METHODS: This prospective open-label study randomized lesions 1:1 to receive NTAP or SOC (cryotherapy). Patients were treated at 4-week intervals for a maximum of 3 treatments. They were evaluated 4 weeks postfinal treatment for sustained response. Primary outcome was lesion response. RESULTS: One hundred twelve VV lesions in 14 patients were enrolled. Patients were mostly White (92.9%) males (71.4%) with mean age of 9.5 [±2.5] years. Responses of SOC- and NTAP-treated lesions, respectively, included no response (5.4%, 7.1%); partial response (33.9%, 41.1%); and complete resolution (60.7%, 51.8%; P value = .679). Patients were more likely to report pain in SOC lesions post-treatment (P value <.001). No significant adverse events (AEs) occurred. LIMITATIONS: Limitations include single-site, maximum of 3 treatments, and short post-treatment follow-up. CONCLUSION: NTAP is an efficacious, safe intervention for treatment of VV in children.

Effect of rigorous fluid management using monitoring of ECW ratio by bioelectrical impedance analysis in critically ill postoperative patients: A prospective, single-blind, randomized controlled study.

BACKGROUND & AIMS: Precise assessment of postoperative volume status is important to administrate optimal fluid management. Bioelectrical impedance analysis (BIA) which measures the body composition using electric character. Extracellular water (ECW) ratio by BIA represented as the ratio of ECW to total body water (TBW) and is known to reflect the hydration status. Based on this, we aimed to determine whether aggressive fluid control using ECW ratio could improve clinical outcomes through a single blind, randomized controlled trial. METHODS: From November 2021 to December 2022, intensive care unit (ICU) patients admitted after surgery were randomly assigned to an intervention group or a control group whether postoperative fluid management was controlled via BIA. Among patients in the intervention group, dehydrated patients received a bolus infusion with crystalloid fluid whereas diuretics were administrated to overhydrated patients until the value of ECW ratio fell within its normal setting range (0.390-0.406). Contrarily, BIA was performed once a day for the control group. Patients in the control group received traditional fluid treatment regardless of BIA results. Primary outcome was in-hospital mortality in two groups. The secondary outcomes were postoperative morbidities, 28-day mortality. RESULTS: 77 patients of the intervention group and 90 patients of the control group were finally analyzed. The in-hospital mortality (0 in intervention, 4.4% in control, p = 0.125) and 28-day mortality (1.3% in intervention, 14.4% in control, p = 0.002) showed lower incidence in the intervention group than in the control group. In multivariate analysis, the overhydrated status whose ECW ratio exceeding 0.406 [odds ratio (OR): 2.731, 95% confidence interval (CI): 1.001-7.663, p = 0.049] and high capillary leak index (CLI) value at ICU admission (OR: 1.024, 95% CI: 1.008-1.039, p = 0.002) were risk factors of postoperative morbidities. Regarding the 28-day mortality, high CLI value (OR: 1.025, 95% CI: 1.002-1.050, p = 0.037) and traditional strategy without BIA monitoring (OR: 9.903, 95% CI: 1.095-89.566, p = 0.041) were the significant predisposing factors. CONCLUSION: Our results revealed the rigorous fluid treatment with volume control based on ECW ratio by BIA failed to achieve significant improvement in in-hospital mortality, but it could reduce 28-day mortality of ICU patients. Monitoring of ECW ratio may help establish optimal fluid treatment strategies for postoperative ICU patients who are susceptible to fluid imbalances with fluid overload. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06097923, retrospectively registered on October 16, 2023, https://clinicaltrials.gov/study/NCT06097923?term=NCT06097923&rank=1.

Test-reduced teaching for stimulation of intrinsic motivation (TRUST): a randomized controlled intervention study.

BACKGROUND: The anatomy dissection course is a major part of the first two years of the traditional medical curriculum in Germany. The vast amount of content to be learned and the repeated examination is unanimously perceived by students and teachers as a major stress factor that contributes to the increase of psychosocial stress during the first two years of the course of study. Published interventions for specific stress reduction are scarce. METHODS: In a randomized, controlled design two intervention groups were compared with a control group (CG) over the whole dissection course (nine measuring points before, during and after first and second semester). The 'Stress Management intervention (IVSM)' targeted at the setting of personal standards, the 'Friendly Feedback intervention (IVFF)' at the context of frequent testing. Quantitative surveys were distributed at nine measuring points. The questionnaire comprised validated instruments and self-developed items regarding stress, positive and negative affect, anxiety, intrinsic and extrinsic motivation, self-efficacy, and perceived performance. RESULTS: Out of 195 students inscribed in the dissection course, 166 (85%) agreed to participate in the study. The experience of stress during the dissection course was significantly higher in the CG than in the IVFF. Anxiety and negative affect were lower in students of the IVFF while positive affect, intrinsic motivation, and self-efficacy were higher than in the CG. For anxiety and negative affect in the IVSM this was especially seen at the end of the second semester. The self-perceived increase in both knowledge and preparedness for the first big oral and written examination did not differ between the study groups. About three quarters of the participants would choose the intervention 'Friendly Feedback' if given the choice. CONCLUSIONS: Replacing formal tests with friendly feedback has proven to be an effective measure to reduce stress and negative affect and foster positive affect, self-efficacy, and intrinsic motivation, while it did not impair self-perceived academic performance.

The impact of hydrogen inhalation therapy on blood reactive oxygen species levels: A randomized controlled study.

Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 h. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%. METHODS: ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent. CONCLUSIONS: Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.

Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study.

BACKGROUND: Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC. METHODS: ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46-55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33-43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%). CONCLUSIONS: Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.

Health Coaching Intervention to Improve Self-Care Management of Hypertension Among Older People in Indonesia: A Randomized Controlled Study Protocol.

Purpose: One-third of the global population is predicted to be diagnosed with hypertension (HTN) in 2025, with the percentage highest among older people. Without proper self-care management, uncontrolled HTN causes negative health consequences and decreases the quality of life. The previous scoping review identified various challenges that older adults may face in dealing with HTN and that effective approaches should consider each individual's circumstances and attributes. This study aims to investigate the efficacy and sustainable impact of an Indonesian adaptation of an 8-week nurse health coaching intervention on self-care management and self-efficacy among older people with HTN. Patients and Methods: The coaching sessions will last for 30 min weekly for 8 weeks. The data will be measured at three points: baseline (initial), 1 week after the eighth health coaching session, and 3 months after concluding the intervention. Discussion: This study will be the first health coaching intervention research based on motivational interviewing and cognitive behavioral therapy approach with Indonesian background adjustment. The study result will help develop a guideline for nurses and other health workers providing health coaching for older people in Indonesia and other countries with similar characteristics in terms of sociodemographics or lifestyle. Trial Registration: thaiclinicaltrials.org Identifier: TCTR20230410001 (Date of registration: April 9, 2023).

Quality controlled YouTube content intervention for enhancing health literacy and health behavioural intention: A randomized controlled study.

Background: Individuals increasingly turn to the Internet for health information, with YouTube being a prominent source. However, the quality and reliability of the health information vary widely, potentially affecting health literacy and behavioural intentions. Methods: To analyse the impact of health information quality on health literacy and behavioural intention, we conducted a randomized controlled trial using a quality-controlled YouTube intervention. Health information quality on YouTube was evaluated using the Global Quality Score and DISCERN. We randomly allocated (1 : 1) to the intervention group to watch the highest quality-evaluated content and to the control group to watch the lowest quality-evaluated content. Health literacy and health behavioural intention were assessed before and after watching YouTube. The trial was set for two different topics: interpreting laboratory test results from health check-up and information about inflammatory bowel disease (IBD). Results: From 8 April 2022 to 15 April 2022, 505 participants were randomly assigned to watch either high-quality content (intervention group, n = 255) or low-quality content (control group, n = 250). Health literacy significantly improved in the intervention group (28.1 before and 31.8 after; p < 0.01 for health check-up; 28.3 before and 31.3 after; p < 0.01 for IBD). Health behavioural intention significantly improved in the intervention group (3.5 before and 4.1 after; p < 0.01 for health check-up; 3.6 before and 4.0 after; p < 0.01 for IBD). Control groups had no such effect. Conclusion: High-quality health information can enhance health literacy and behavioural intention in both healthy individuals and those with specific conditions like IBD. It stresses the significance of ensuring reliable health information online and calls for future efforts to curate and provide access to high-quality health content.

The Efficacy and Safety of Roxadustat for the Treatment of Posttransplantation Anemia: A Randomized Study.

Introduction: Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of posttransplantation anemia (PTA). Methods: A total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed-up with every 4 weeks. The primary end points were the change in Hb levels and response rate throughout the randomized period. Results: A total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dl in the experimental group and 11.19 g/dl in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8 to 12 were significant between the 2 groups. The adverse event profiles were comparable between the 2 groups. Conclusion: Roxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.

Efficacy of acupuncture for a cough-related symptom cluster in patients with lung cancer: A randomized controlled trial.

PURPOSE: This study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients. METHODS: Between December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons. RESULTS: Compared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = -0.32, 95% CI, -0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = -0.11, 95% CI, -0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = -0.05, 95% CI, -0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = -0.66, 95% CI, -0.99 to 0.33, P < 0.001) post-intervention. CONCLUSIONS: Acupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath.

The effect of Transition to Adulthood Training Program for mothers of young adults with intellectual disability on family quality of life and perceived stress level: A pilot randomized controlled study.

Families cannot easily identify and cope with the changing health problems and needs of children transitioning into adulthood. This pilot randomized controlled study aims to improve the family's quality of life and reduce mothers' perceived stress levels by implementing an educational program (Transition to Adulthood Training Program - TATP). A total of 33 mothers of children with intellectual disabilities were randomly assigned to the groups. Data were collected using the Personal Information Form, Beach Center Family Quality of Life (BCFQOL), and Perceived Stress Scale. The intervention group showed a significant increase in the BCFQOL mean score rather than the control group (p<.001). There was a significant decrease in the perceived stress scores of the mothers in the intervention group after the TATP training sessions (p<0.05). The TATP intervention not only increased the quality of family life for these mothers but also led to a reduction in their perceived stress levels.