A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis.

BACKGROUND: Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits. METHODS: In this phase 3, 12-month, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients who had had an inadequate response to or who had a history of unacceptable side effects with ursodeoxycholic acid to receive oral seladelpar at a dose of 10 mg daily or placebo. The primary end point was a biochemical response, which was defined as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a decrease of 15% or more from baseline, and a normal total bilirubin level at month 12. Key secondary end points were normalization of the alkaline phosphatase level at month 12 and a change in the score on the pruritus numerical rating scale (range, 0 [no itch] to 10 [worst itch imaginable]) from baseline to month 6 among patients with a baseline score of at least 4 (indicating moderate-to-severe pruritus). RESULTS: Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy. A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001). Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001). Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, -3.2 vs. -1.7; least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5, P = 0.005). Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively. CONCLUSIONS: In this trial involving patients with primary biliary cholangitis, the percentage of patients who had a biochemical response and alkaline phosphatase normalization was significantly greater with seladelpar than with placebo. Seladelpar also significantly reduced pruritus among patients who had moderate-to-severe pruritus at baseline. The incidence and severity of adverse events were similar in the two groups. (Funded by CymaBay Therapeutics; RESPONSE ClinicalTrials.gov number, NCT04620733; EudraCT number, 2020-004348-27.).

Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis.

BACKGROUND AND AIMS: Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar's antipruritic effects and IL-31 and bile acid levels in patients with PBC. APPROACH AND RESULTS: IL-31 levels were quantified in serum samples from the ENHANCE study of patients with PBC receiving daily oral doses of placebo (n = 55), seladelpar 5 mg (n = 53) or 10 mg (n = 53) for 3 months, and for healthy volunteers (n = 55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0-10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS ( r = 0.54, p < 0.0001), and total ( r = 0.54, p < 0.0001) and conjugated bile acids (up to 0.64, p < 0.0001). Decreases in IL-31 were observed with seladelpar 5 mg (-30%, p = 0.0003) and 10 mg (-52%, p < 0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS ≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS < 2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids ( r = 0.63, p < 0.0001) in the seladelpar 10 mg group. CONCLUSIONS: Seladelpar decreased serum IL-31 and bile acids in patients with PBC. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement, suggesting a mechanism to explain seladelpar's antipruritic effects.

Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis.

Seladelpar, a selective peroxisome proliferator-activated receptor δ (PPARδ) agonist, improves markers of hepatic injury in human liver diseases, but histological improvement of nonalcoholic steatohepatitis (NASH) and liver fibrosis has been challenging with any single agent. To discover how complementary agents could work with seladelpar to achieve optimal outcomes, this study evaluated a variety of therapeutics (alone and in combination) in a mouse model of NASH. Mice on a high-fat amylin liver NASH (AMLN) diet were treated for 12 wk with seladelpar, GLP-1-R (glucagon-like peptide-1 receptor) agonist liraglutide, apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib, farnesoid X receptor (FXR) agonist obeticholic acid, and with seladelpar in combination with liraglutide or selonsertib. Seladelpar treatment markedly improved plasma markers of liver function. Seladelpar alone or in combination resulted in stark reductions in liver fibrosis (hydroxyproline, new collagen synthesis rate, mRNA indices of fibrosis, and fibrosis staining) compared with vehicle and the other single agents. Robust reductions in liver steatosis were also observed. Seladelpar produced a reorganization of metabolic gene expression, particularly for those genes promoting peroxisomal and mitochondrial lipid oxidation. In summary, substantial improvements in NASH and NASH-induced fibrosis were observed with seladelpar alone and in combination with liraglutide in this model. Broad gene expression analysis suggests seladelpar should be effective in concert with diverse mechanisms of action.NEW & NOTEWORTHY NASH is a chronic, progressive, and increasingly problematic liver disease that has been resistant to treatment with individual therapeutics. In this study using a diet-induced mouse model of NASH, we found that the PPARδ agonist seladelpar reduced fibrosis and NASH pathology alone and in combinations with a GLP-1-R agonist (liraglutide) or an ASK1 inhibitor (selonsertib). Liver transcriptome analysis comparing each agent and coadministration suggests seladelpar should be effective in combination with a variety of therapeutics.

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Survey on caregiver competency and retraining needs.

OBJECTIVES: This study investigated caregivers' job image, abilities, and educational needs, which are rapidly increasing owing to an aging society. DESIGN: A self-administered written survey was conducted at 12 general hospitals in Korea from February 1, 2022 to March 15, 2023. SAMPLE: A total of 451 caregivers participated in the survey as subjects of analysis, and 560 nurses participated as external observers. MEASUREMENTS: The caregivers' self-assessment results regarding job performance, educational needs, and retraining needs were compared with those of external observers. RESULTS: Caregivers evaluated themselves significantly higher in all areas of job performance compared to the evaluations of external observers. In particular, the caregivers' self-evaluation of their abilities in "Recording and Reporting," "Basic Resuscitation," "Safety and Infection Control," and "Understanding Major Illnesses" was different from the evaluation of nurses. Both the caregivers and external observers agreed on the need for caregiver retraining, with 1-2 hours of supplementary training every 12 months being the most preferred amount of retraining. CONCLUSIONS: There was a significant difference between caregivers' self-evaluations of their capabilities and the external observers' evaluations. Therefore, systematic professional caregiver retraining is necessary.

Efficacy of a virtual nursing simulation-based education to provide psychological support for patients affected by infectious disease disasters: a randomized controlled trial.

BACKGROUND: Virtual simulation-based education for healthcare professionals has emerged as a strategy for dealing with infectious disease disasters, particularly when training at clinical sites is restricted due to the risk of infection and a lack of personal protective equipment. This research evaluated a virtual simulation-based education program intended to increase nurses' perceived competence in providing psychological support to patients affected by infectious disease disasters. METHODS: The efficacy of the program was evaluated via a randomized controlled trial. We recruited 104 nurses for participation in the study and allocated them randomly and evenly to an experimental group and a control group. The experimental group was given a web address through which they could access the program, whereas the control group was provided with a web address that directed them to text-based education materials. Data were then collected through an online survey of competence in addressing disaster mental health, after which the data were analyzed using the Statistical Package for the Social Sciences(version 23.0). RESULTS: The analysis showed that the experimental group's disaster mental health competence (F = 5.149, p =.026), problem solving process (t = 3.024, p =.003), self-leadership (t = 2.063, p =.042), learning self-efficacy (t = 3.450, p =.001), and transfer motivation (t = 2.095, p =.039) significantly statistically differed from those of the control group. CONCLUSIONS: A virtual nursing simulation-based education program for psychological support can overcome limitations of time and space. The program would also be an effective learning resource during infectious disease outbreaks. CLINICAL TRIAL REGISTRATION: This Korean clinical trial was retrospectively registered (21/11/2023) in the Clinical Research Information Service ( https://cris.nih.go.kr ) with trial registration number KCT0008965.

Professional quality of life, resilience, posttraumatic stress and leisure activity among intensive care unit nurses.

BACKGROUND: Nurses working in the intensive care unit (ICU) often experience posttraumatic stress due to being exposed to pain, death, disease and surrogate trauma. Thus, it is necessary to investigate ways to enhance their coping abilities and improve their professional quality of life. AIM: This study explores factors related to professional quality of life, resilience and posttraumatic stress of ICU nurses and provides basic data for the development of psychological support programmes to address. METHODS: The participants in this cross-sectional study consisted of 112 ICU nurses working at a general hospital in Seoul, Korea. Data were collected using self-report questionnaires on general characteristics, professional quality of life, resilience and posttraumatic stress and analysed using IBM SPSS for Windows version 25. FINDINGS: Professional quality of life showed a significant positive correlation with nurses' resilience, whereas posttraumatic stress was significantly negatively correlated with professional quality of life. Among participants' general characteristics, leisure activity showed the strongest positive correlation with professional quality of life and resilience and a significant negative correlation with posttraumatic stress. CONCLUSION: This study explored the correlations among resilience, posttraumatic stress and professional quality of life of ICU nurses. Further, we found that leisure activities are associated with their higher resilience and lower posttraumatic stress. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Policy development and organisational supports are required to promote various club activities and stress reduction programmes for clinical nurses in order to increase their professional quality of life and resilience as well as prevent posttraumatic stress.

Adeno-associated virus (AAV) 9-mediated gene delivery of Nurr1 and Foxa2 ameliorates symptoms and pathologies of Alzheimer disease model mice by suppressing neuro-inflammation and glial pathology.

There is a compelling need to develop disease-modifying therapies for Alzheimer's disease (AD), the most common neuro-degenerative disorder. Together with recent progress in vector development for efficiently targeting the central nervous system, gene therapy has been suggested as a potential therapeutic modality to overcome the limited delivery of conventional types of drugs to and within the damaged brain. In addition, given increasing evidence of the strong link between glia and AD pathophysiology, therapeutic targets have been moving toward those addressing glial cell pathology. Nurr1 and Foxa2 are transcription/epigenetic regulators that have been reported to cooperatively regulate inflammatory and neurotrophic response in glial cells. In this study, we tested the therapeutic potential of Nurr1 and Foxa2 gene delivery to treat AD symptoms and pathologies. A series of functional, histologic, and transcriptome analyses revealed that the combined expression of Nurr1 and Foxa2 substantially ameliorated AD-associated amyloid ß and Tau proteinopathy, cell senescence, synaptic loss, and neuro-inflammation in multiple in vitro and in vivo AD models. Intra-cranial delivery of Nurr1 and Foxa2 genes using adeno-associated virus (AAV) serotype 9 improved the memory and cognitive function of AD model mice. The therapeutic benefits of gene delivery were attained mainly by correcting pathologic glial function. These findings collectively indicate that AAV9-mediated Nurr1 and Foxa2 gene transfer could be an effective disease-modifying therapy for AD.

Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes of Staphylococcus aureus Bacteremia.

BACKGROUND: Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. METHODS: Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. RESULTS: Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). CONCLUSION: The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.

Neurofeedback Effect on Symptoms of Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis.

Posttraumatic stress disorder (PTSD) encompasses various psychological symptoms and a high early dropout rate due to treatment unresponsiveness. In recent years, neurofeedback has been implemented to control PTSD's psychological symptoms through physiological brain regulation. However, a comprehensive analysis concerning its efficacy is lacking. Therefore, we conducted a systematic review and meta-analysis to determine neurofeedback's effect on reducing PTSD symptoms. We analyzed randomized and non-randomized controlled trials (RCTs) from 1990 to July 2020, evaluating neurofeedback treatments for those diagnosed with PTSD and their symptoms. In addition, we calculated the standardized mean difference (SMD)using random-effects models to estimate effect sizes. We assessed ten articles comprising 276 participants, with a - 0.74 SMD (95% confidence interval = - 0.9230, - 0.5567), 42% I2, moderate effect size, and - 1.40 to -0.08 prediction intervals (PI). Neurofeedback was more effective for complex trauma PTSD patients than single trauma. Increasing and lengthening sessions are more effective than fewer, condensed ones. Neurofeedback positively affected arousal, anxiety, depression, and intrusive, numbing, and suicidal thoughts. Therefore, neurofeedback is a promising and effective treatment for complex PTSD.

What influenced frontline nurses' mental health during the early phase of the COVID-19 pandemic.

AIM: This cross-sectional study aimed to investigate the factors that affected the mental health of Korean nurses caring for coronavirus disease 2019 (COVID-19) patients, causing posttraumatic stress disorder, depression, anxiety, and sleep disorders. BACKGROUND: Infectious disease outbreaks like COVID-19 affect the mental health not only of those who contract the disease but also of nurses caring for affected patients. INTRODUCTION: To address health issues effectively, it is essential to comprehend how to prevent them. Therefore, it is necessary to scrutinize the origins of COVID-19-related health concerns and devise measures to prevent potential problems. METHOD: We used an online survey to collect data from 136 nurses caring for COVID-19 patients during the initial stage of the pandemic. The data were analyzed using the one-way analysis of variance and a simple logistic regression. RESULTS: The findings confirmed a high prevalence of posttraumatic stress disorder among nurses, with symptoms of depression, anxiety, and sleep problems. DISCUSSION: Our research has shown that it is important not to exacerbate the difficulties that nurses face after their activities. Therefore, it proposes for creating environmental structures that mitigate predictable challenges such as workload from various tasks, sleep disturbances, and hopelessness, rather than focusing on personal vulnerabilities. CONCLUSION: Timely attention to influencing factors can reduce the risk to nurses' mental health, so we need to plan preventive measures that reflect the influencing factors to prepare for future pandemics. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Continuous monitoring of the mental health status of nurses responding to a global health crisis and the development of appropriate psychological support programs and policies for creating a conducive work environment are necessary.

A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis.

BACKGROUND & AIMS: We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk of disease progression (alkaline phosphatase [ALP] ≥1.67xupper limit of normal [ULN]) who were receiving or intolerant to ursodeoxycholic acid. METHODS: In this 52-week, phase II, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5 mg/day (n = 53) or 10 mg/day (n = 55) or assigned to 2 mg/day (n = 11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10 mg/day. The primary efficacy endpoint was ALP change from baseline to Week 8. RESULTS: Mean baseline ALP was 300, 345, and 295 U/L in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean ± standard error ALP reductions from baseline were 26 ± 2.8%, 33 ± 2.6%, and 41 ± 1.8% in the 2 mg (n = 11), 5 mg (n = 49), and 10 mg (n = 52) cohorts (all p ≤0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, composite response (ALP <1.67xULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events, and 4 patients discontinued due to adverse events. CONCLUSIONS: Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus. GOV NUMBER: NCT02955602 CLINICALTRIALSREGISTER. EU NUMBER: 2016-002996-91 LAY SUMMARY: Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10 mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores.

Can Bone Erosion in Axial Spondyloarthropathy be Detected by Ultrashort Echo Time Imaging? A Comparison With Computed Tomography in the Sacroiliac Joint.

BACKGROUND: Structural lesion evaluation in axial spondyloarthropathy (SpA) can improve accuracy of diagnosis. However, structural lesions (bone erosions) are difficult to be assessed using conventional MRI compared to computed tomography (CT). PURPOSE: To evaluate the diagnostic performance of ultrashort echo time (UTE) for detecting bone erosion in axial SpA compared to T1WI and three-dimensional double-echo steady-state (3D DESS) imaging using CT as the reference standard. STUDY TYPE: Retrospective. POPULATION: Fourteen patients (eight females, 57.1%) and 14 healthy controls (seven females, 50.0%) who underwent sacroiliac (SI) joint MRI and CT. FIELD STRENGTH/SEQUENCE: 3 T; TSE T1WI, 3D DESS, 2D UTE. ASSESSMENT: The bilateral SI joints were assessed for bone erosion. Three observers scored bone erosion for all three sequences of MRI. CT was used as the gold standard. Diagnostic confidence in axial SpA was measured based on a four-point confidence score. STATISTICAL TESTS: Correlation of erosion scores between CT and MRI were evaluated using Spearman's correlation test. Sensitivity, specificity, and positive-negative predictive values were calculated. Confidence scores were compared using the Wilcoxon sum rank test. Statistical significance was set at P < 0.05. RESULTS: Compared with erosion scores of CT, the correlation coefficients for each MRI sequence showed significant low-to-high positive correlations (0.39-0.72). UTE imaging showed the highest correlation coefficients for all observers (0.70, 0.72, and 0.67, respectively). The specificity of UTE imaging was equal or higher than those of T1WI and 3D DESS for all observers (0.86 vs. 0.71 vs. 0.57; 0.93 vs. 0.71 vs. 0.57; 0.79 vs. 0.79 vs. 0.43). All observers had the highest confidence in interpreting UTE imaging for detecting bone erosion among the three sequences (3.5, 3.4, and 3.3 for UTE; 3.1, 3.0, and 2.6 for T1WI; and 3.2, 2.7, and 2.4 for DESS). DATA CONCLUSION: UTE imaging can detect bone erosions in patients with axial SpA and show higher specificity than conventional T1WI and 3D DESS. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Seladelpar improved measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) can result in life-altering cholestatic pruritus and fatigue, but treatment options are limited. Seladelpar, a peroxisome proliferator-activated receptor-delta (PPARδ) agonist, has demonstrated potent anti-cholestatic effects in clinical studies. This open-label, uncontrolled phase 2 study in PBC patients evaluated the effects of 1-year of seladelpar treatment on measures of pruritus and quality of life. METHODS: Self-reported experiences of 101 PBC patients were collected at baseline and after 1 year of seladelpar treatment using the pruritus visual analog scale (VAS), 5D-itch scale, and PBC-40 questionnaires along with bile acid profiles. RESULTS: In patients with moderate-to-severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in 5/10 mg and 10 mg treatment groups, respectively. After 1 year, patients reporting improvement substantially outnumbered those who worsened in the total 5-D itch (including individual domains) and PBC-40 (itch and fatigue domains) questionnaires. Improvement in sleep disturbance at 1-year was reported in 81% (5/10 mg) and 78% (10 mg) of the patients with baseline itch-related sleep disturbance by 5-D itch score with similar results using the PBC-40 sleep questionnaire. Seladelpar-treated patients had significant reductions of 46% (5/10 mg) and 31% (10 mg) in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids. CONCLUSIONS: Seladelpar treatment for 1 year led to consistent improvement in both symptom burden and biochemical response, suggesting its potential as a single agent to address two key unmet needs in PBC patients.

A simulation-based nursing education of psychological first aid for adolescents exposed to hazardous chemical disasters.

BACKGROUND: Simulation-based education facilitates a learner-centered experience, which has been found to be effective in improving clinical performance, problem-solving ability, and self-confidence in nursing practice. The objective of this study was to develop and test a psychological first aid simulation-based education program for nurses caring for adolescents exposed to hazardous chemical disasters. METHODS: This study employed a nonequivalent pre and post-control group research design. The simulation-based education program was developed, and the participants were 30 nurses working in a medical center who were randomly assigned to the experimental, comparison, and control groups. The collected data were statistically analyzed using IBM SPSS Statistics for Windows, Ver. 22.0. RESULTS: The nurses who participated in the simulation-based education program showed statistically significantly improved psychological first aid performance knowledge, competence, and self-efficacy compared to those in the other groups. CONCLUSIONS: Nursing simulation programs could help to improve nurses' performance in mental health care and psychological support for adolescents suffering from hazardous chemical disasters.

Effects of Nursing Care Using Binaural Beat Music on Anxiety, Pain, and Vital Signs in Surgery Patients.

PURPOSE: This study investigated the effects of binaural beat music on anxiety, pain, and vital signs in Korean surgical patients. DESIGN: This study used a non-equivalent control group pre-and post-test design. METHODS: This study included 54 patients who underwent spinal nerve plastic surgery under local anesthesia. The experimental group listened to binaural beat music twice, using headphones (20 minutes before surgery and 30 minutes after surgery). We measured the participants' pain and anxiety levels using a visual analog scale for pain and anxiety. In addition, we checked the participants' systolic and diastolic blood pressure and heart rate using a blood pressure monitor. FINDINGS: The experimental group displayed significantly lower anxiety and pain scores than the control group after the intervention. Meanwhile, systolic and diastolic blood pressure did not show any statistically significant differences between the groups. However, the experimental group had a significantly lower pulse rate than the control group. CONCLUSION: Our research findings showed that using binaural beat music in the nursing care of surgical patients under local anesthesia can effectively reduce postoperative pain and anxiety, contributing to improved mental health and physical well-being after surgery.

The mediating effect of life satisfaction and the moderated mediating effect of social support on the relationship between depression and suicidal behavior among older adults.

OBJECTIVES: This study aimed to investigate the effect of depression on suicidal behavior among older adults and identify the mediating effect of life satisfaction on the relationship between depression and suicidal behavior. The moderated mediating effects of social support through life satisfaction were also verified in the relationship between depression and suicidal behavior among older adults. METHODS: A total of 1375 people aged 65 years or older living in J city, South Korea, were recruited to complete a survey on depression, life satisfaction, suicidal behavior, and social support. Data were analyzed using SPSS24.0 and SPSS PROCESS Macro. RESULTS: The results showed that the effect of depression on suicidal behavior was mediated by life satisfaction, and the effect of life satisfaction on suicidal behavior varied according to the level of social support. Moreover, depression negatively affected life satisfaction, increasing the risk of suicidal behavior, and social support decreased suicidal behavior. Finally, the mediating effect of depression leading to suicidal behavior through life satisfaction was moderated by social support. CONCLUSIONS: These findings suggest that it is necessary not only to find interventions for older adults to increase their physical, mental, and socioeconomical satisfaction with life, but also to build social networks that increase social support for them.

Effects of a psychological first aid simulated training for pregnant flood victims on disaster relief worker's knowledge, competence, and self-efficacy.

AIMS: To develop a simulation-based psychological first aid (PFA) education program for disaster relief workers and verify its impact on their PFA knowledge, PFA performance competence, and self-efficacy. BACKGROUND: Relief workers should be provided with systematic education on their required knowledge and skills; however, PFA training for relief workers is lacking, which results in ineffective mental health support during disaster situations. METHODS: This study adopted a non-equivalent control group pre-posttest quasi-experimental design. Thirty relief workers from mental health welfare centers in Seoul and Gyeonggi Province participated. The experimental group received a PFA lecture, a simulation-based PFA education program, and access to the Psychological Life Support (PLS) mobile application, which provides information on disaster situations and PFA techniques. The comparison group received a PFA lecture. The control group was provided with self-learning PFA materials. RESULTS: Among the three groups, the experimental group showed the greatest improvement in PFA knowledge, PFA performance competence, and self-efficacy from pretest to posttest, which was statistically significant. CONCLUSIONS: This study demonstrated the effectiveness of the simulation-based PFA education program combined with a PFA lecture and the PLS mobile app as complementary methods to assist relief workers in applying PFA in disaster situations.

Nicotinamide-induced mouse embryo developmental defect rescued by resveratrol and I-CBP112.

Cell cycle of mouse embryo could be delayed by nicotinamide (NAM). Histone H3 lysine 56 (H3K56ac) acetylation plays an important role in mammalian genomic stability and the function of this modification in mouse embryos is not known. Hence, we designed to study the effects of NAM-induced oxidative stress on the developmental ability of mouse embryos, on the acetylation of H3K56ac and the possible functions of this modification related to mouse embryo development. Treatment with NAM (10, 20, or 40 mmol/L for 24 or 48 hr) during in vitro culture significantly decreased developmental rate of blastocyst (24 hr: 90.2 vs. 81.2, 43.2, and 18.2, with p > .05, p < .01, respectively; 48 hr: 89.3 vs. 53.2%, 12.1%, and 0% with p < .05, respectively). NAM treatment (20 mmol/L) for 6 and 31 hr resulted in increased intracellular reactive oxygen species levels in two-cell embryos, and apoptotic cell numbers in blastocysts. Resveratrol (RSV) and I-CBP112 rescued the 20 mmol/L NAM-induced embryo developmental defects. RSV and I-CBP112 increased the level of Sirt1 and decreased the level of H3K56ac induced by NAM in two-cell embryos (p < .05). These data suggest that NAM treatment decreases the expression of Sirt1, which induces high levels of H3K56 acetylation that may be involved in oxidative stress-induced mouse embryo defects, which can be rescued by RSV and I-CBP112.

Not All Green Is Tophi: The Importance of Optimizing Minimum Attenuation and Using a Tin Filter to Minimize Clumpy Artifacts on Foot and Ankle Dual-Energy CT.

OBJECTIVE. The clumpy artifact has a high misdiagnosis rate, but the artifact has not been well studied. The aims of this study were to evaluate the frequency and location of clumpy artifacts, the rate of misdiagnosis of clumpy artifacts as gout, and the effects of raising the minimum attenuation value and using a selective photon shield in dual-energy CT (DECT). MATERIALS AND METHODS. Forty patients without gout who underwent foot and ankle DECT were enrolled in this study. Images in both sets were randomly assigned a minimum attenuation of 130 HU or 150 HU. Three radiologists independently checked all images for presence, volume, and location of green color-coded pixelation and graded their findings according to a 4-point confidence scale, frequency, and volume. Misdiagnosis rate and misdiagnosis score were compared using the Wilcoxon signed rank and McNemar tests. RESULTS. In set 1, the frequency of clumpy artifacts in DECT with the minimum attenuation set to 130 HU and 150 HU were 81% and 68%, respectively. For all three readers, the misdiagnosis rate and misdiagnosis score decreased when changing the minimum attenuation from 130 HU to 150 HU. In set 2, with the minimum attenuation set to 130 HU, the frequency of the clumpy artifact was 44%; with the minimum attenuation set to 150 HU, no clumpy artifacts were seen. CONCLUSION. Clumpy artifacts occurred frequently in DECT without a tin filter. Setting the minimum attenuation to the higher value of 150 HU reduced the frequency of clumpy artifacts, and adding a tin filter to DECT greatly reduced their occurrence.