Clinical Trials Registry Research Articles

Effect of classical prolotherapy technique in knee osteoarthritis for a sample of Egyptian population: clinical and imaging study

BackgroundKnee osteoarthritis (KOA) is a progressive musculoskeletal disease that leads to physical impairment and disability. Several nonoperative therapeutic options have been proposed to reduce symptoms, improve physical function, and prevent disability. One of these therapeutic options is dextrose prolotherapy (DPT). The current study aimed to investigate the efficacy of DPT in the treatment of symptomatic KOA and to evaluate its potential proliferative role as assessed by musculoskeletal ultrasound (MSUS) and magnetic resonance imaging (MRI).ResultsSeventeen knees (21.25%) dropped out, leaving 63 knees in the final analysis (57 females and 6 males, aged 41–74 years) with KOA. At 24-week follow-up, the visual analogue scale and overall Western Ontario and McMaster Universities scores showed significant improvement (P < 0.001). Moreover, a highly significant increase in cartilage thickness with a decrease in effusion grade and meniscal extrusion was observed by MSUS (P < 0.001). By MRI, there was a statistically significant decrease in effusion grade (P = 0.013) and meniscal extrusion (P = 0.005) and a highly significant increase in cartilage thickness (P < 0.001). Logistic analysis showed that lower patients’ body mass index (BMI) at baseline was a significant predictor for clinical improvement following DPT.ConclusionDPT might be considered a relatively safe minimally invasive intervention for the treatment of KOA with high adherence and satisfaction. It may lead to significant clinical and structural improvement in patients with KOA. Furthermore, lower BMI is a predicting factor for better clinical response to DPT.Trial registrationThe study was registered prospectively in ClinicalTrials.gov: clinical trial registration number NCT04178304 on 21 November 2019, https://register.clinicaltrials.gov/XXX.

Correlation of screen exposure to stress, learning, cognitive and language performance in children.

The omnipresence of mobile screens and convenience to operate them has led to increased screen time for young children whereas the sequelae of prolonged exposure are not known yet. 70 refugee children (RG) and 111 children of a clinical comparison group (CG) from a help-seeking population (age: M = 5.10; SD = 1.11; range 3.00-6.97years) were assessed concerning their amount of daily screen exposure time in relation to parental education and distress. Salivary cortisol was collected as a marker for biological stress and children were tested concerning learning performance, non-verbal IQ and vocabulary with the Kaufmann Assessment Battery for Children (KABC-II). Language skills were assessed in educator rating. The amount of children's screen exposure was negatively related to parental education and positively to distress. In the CG, higher amounts of screen time were associated with elevated cortisol levels and lower learning scores. On both measures, the RG and CG only differed in the condition of screen time less than one hour/day, for higher amounts of screen time the CG approached the more problematic scores of the RG. Whereas in the whole sample the amount of screen time was negatively correlated to language performance, it was not correlated to non-verbal IQ-scores. As a higher amount of media exposure in our clinical comparison group is associated with elevated biological stress, decreased learning and lower language performance, it should be classified as a relevant environmental factor and regularly considered in clinical assessments of children and therapeutical interventions, especially in vulnerable subgroups. German clinical trials register, registration number: DRKS00025734, date: 07-23-2021.

Clinical usefulness of digital twin guided virtual amiodarone test in patients with atrial fibrillation ablation

It would be clinically valuable if the efficacy of antiarrhythmic drugs could be simulated in advance. We developed a digital twin to predict amiodarone efficacy in high-risk atrial fibrillation (AF) patients post-ablation. Virtual left atrium models were created from computed tomography and electroanatomical maps to simulate AF and evaluate its response to varying amiodarone concentrations. As the amiodarone concentration increased in the virtual setting, action potential duration lengthened, peak upstroke velocities decreased, and virtual AF termination became more frequent. Patients were classified into effective (those with virtually terminated AF at therapeutic doses) and ineffective groups. The one-year clinical outcomes after AF ablation showed significantly better results in the effective group compared to the ineffective group, with AF recurrence rates of 20.8% vs. 45.1% (log-rank p = 0.031, adjusted hazard ratio, 0.37 [0.14-0.98]; p = 0.046). This study highlights the potential of a digital twin-guided approach in predicting amiodarone’s effectiveness and improving personalized AF management. Clinical Trial Registration Name: The Evaluation for Prognostic Factors After Catheter Ablation of Atrial Fibrillation: Cohort Study, Registration number: NCT02138695. The date of registration: 2014-05. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02138695.

A Pilot Controlled Trial of Relaxation Training Combined with a Video Game Reinforcing Emotional Regulation to Improve Anger Management in Children and Adolescents.

Untreated anger and aggression in youth confer heightened risk for subsequent psychosocial problems. However, engaging youth in treatment for anger can be difficult given barriers to accessing care and high rates of attrition. This study examined whether learning relaxation skills and practicing them using a videogame, whose operation was contingent upon keeping heart rate close to baseline levels, could help children learn to manage anger and aggression. Youth ages 7-17 with elevated levels of anger (N = 39) were randomized to receive the active video game condition or a control game that displayed heart rate but did not stop the game if heart rate became elevated. Youth underwent baseline screening, 6 treatment sessions, and follow-up assessments at 2-weeks and 3-months. Compared to the control condition, children in the active condition demonstrated significantly greater improvements in clinician-rated aggression severity (d = 1.48) and youth-rated emotion dysregulation (d = 3.46) at 2-weeks post-treatment. The active group maintained these improvements at 3-month follow-up, but no longer significantly differed from the control group. Intervention effects were nonsignificant for parent-reported emotion dysregulation and aggression. In addition, the intervention group youth, but not control group, experienced increased time with heart rate below baseline over the course of the 6 sessions. Findings suggest a promising brief intervention for reducing aggression and emotion dysregulation in children while they are waiting for longer-term outpatient therapy. Clinical Trial Registration Number: NCT03270813.

Tooth loss during long-term periodontal therapy in specialized practices – a retrospective cohort study from a periodontal practice-based research network (Perio-PBRN)

ObjectivesTo investigate tooth-specific, clinical tooth-, and patient-related factors associated with tooth loss (TL) in patients with mild to severe periodontitis treated in a periodontal practice-based research network (Perio-PBRN) over at least 5 years.Materials and methodsThe Perio-PBRN consists of five German periodontal practices where clinical data were collected regarding patient age, tooth type, bleeding on probing (BOP), pocket probing depth (PPD), furcation involvement (FI), number of attended appointments, and other variables of interest. The data were evaluated regarding factors influencing TL.ResultsData from 687 patients (aged 54.5 ± 11.1 years) with mild (N = 23, 3.35%), moderate (N = 247, 35.95%) or severe (N = 417, 60.70%) periodontitis and 15,931 teeth over a mean observation period of 6.83 ± 1.40 years per patient were gathered via the Perio-PBRN. In this period, a total of 657 teeth were lost (4.12%, overall TL: 0.14 ± 0.22 teeth/patient/y). The risk of TL was significantly increased for teeth with persistent PPD ≥ 6 mm (hazard ratio: 6.81 [95% confidence interval: 5.07–9.15] in comparison to PPD < 4 mm. Additionally, BOP (3.90 [2.46–6.19]), furcation involvement, jaw, age and tooth type showed a significant influence on TL, while number of visits were not significantly associated with TL.ConclusionsPeriodontal care of patients with moderate to severe disease in specialized practices was associated with a low rate of TL. Known tooth-related prognostic factors were confirmed. However, the results must be interpreted cautiously without knowledge of risk factors such as smoking and diabetes.Clinical relevancePBRNs can help gather large amounts of periodontal practice-level data.Trial registrationThe study was registered in the German Clinical Trials Register (DRKS 00011448).

Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials.

Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We analysed the association between ΔHR from the preceding visit with the primary endpoint of HF hospitalization (HFH) or cardiovascular death using covariate-adjusted Cox proportional hazards models. A total of 13 194 patients (mean age 67 ± 11 years, 67% men, mean LVEF 40 ± 15%) were included. Over a median follow-up of 2.5 years, 3114 patients experienced a first HFH or cardiovascular death event (10.4 events per 100 patient-years). An increase in HR from the preceding visit, compared with no change, was associated with a higher risk (hazard ratio 1.12; 95% confidence interval [CI] 1.10-1.15; p < 0.001 per 5 bpm increase). Conversely, a drop in HR was associated with a lower risk (hazard ratio 0.97; 95% CI 0.94-1.00; p = 0.044 per 5 bpm drop). The prognostic implications of ΔHR were consistent across the range of LVEF and observed regardless of β-blocker use or presence of a permanent pacemaker. Visit-to-visit increases in HR were especially prognostic in patients without atrial fibrillation (pinteraction = 0.006). Across a broad spectrum of patients with chronic HF, increases in HR from a preceding visit independently predicted clinical outcomes. The detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events. Clinical Trial Registration; ClinicalTrials.gov NCT01035255 (PARADIGM-HF), NCT01920711 (PARAGON-HF).

Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.

Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).

Evaluating efficacy and safety of ocrelizumab biosimilar (Xacrel) compared to the originator (Ocrevus) in relapsing multiple sclerosis: a phase III, randomized, equivalency, clinical trial

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of − 0.2 to 0.2 (− 0.002; 95% CI − 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338.

Combined lung and diaphragm ultrasound predicts extubation outcomes in ARDS: a prospective study

BackgroundExtubation failure is a crucial issue for acute respiratory distress syndrome (ARDS). Ultrasound of the lung and diaphragm is individually valuable for predicting extubation outcomes. We aimed to determine whether combined lung and diaphragmatic ultrasound could improve the accuracy of predicting the extubation of ARDS patients.MethodsThis was a prospective cohort study of ARDS patients who were ready for extubation. The lung ultrasound score (LUS), diaphragmatic displacement (DD), diaphragm thickening fraction (DTF), and diaphragmatic-rapid shallow breathing index (D-RSBI) were measured at the end of the spontaneous breathing trial. The primary outcome was extubation success. Logistic regression was used to combine these indicators, and the predictive performance of the single and combined indicators was evaluated through receiver operating characteristic (ROC) curves, the Hosmer–Lemeshow Ĉ‐test, and the Brier score. Multivariate logistic regression was used to determine the association between combined ultrasound indicators and extubation success.ResultsThis study enrolled 132 eligible patients from January 2019 to December 2022. A total of 71% (94/132) of patients were successfully extubated from mechanical ventilation. The combination of LUS and D-RSBI had the largest area under the ROC curves, the lowest Brier score, and the greatest calibration. After formula transformation, LUS + 2.43 × D-RSBI ≤ 14.273 was significantly associated with extubation success in ARDS patients.ConclusionsIn ARDS patients receiving mechanical ventilation, the combination of LUS and D-RSBI was more accurate than a single parameter alone in predicting extubation outcomes. This combined approach could help refine extubation protocols in critical care.Clinical trial registration This study is registered online with the Chinese Clinical Trial Registry (ChiCTR), http://www.chictr.org.cn, ChiCTR1800019340 (Registration time: 2018/11/06).

Uptake of health economic evaluations alongside clinical trials in Australia: an observational study.

Australia's clinical trials sector is highly productive with continued sector investment needed to enhance research impact. Generating economic evidence alongside trials has the potential to facilitate the implementation of trial results into practice. Ascertaining the use of health economic evaluations alongside clinical trials can assist in determining whether clinical trials fully realize and operationalize their potential to change policy and practice. The aims of this study were to ascertain the uptake of health economic evaluations alongside Australian-led clinical trials and explore associations between uptake and trial characteristics. This observational study comprised a descriptive analysis of clinical trials registries, a cross-sectional survey of Australian Clinical Trials Alliance (ACTA) networks, and a subgroup analysis of completed acute care trials. Descriptive analyses of trial registrations were conducted, with logistic regressions used to identify predictors of proposing and subsequently publishing a health economic evaluation alongside acute care trials. Few randomized Australian-led clinical trials (11% of 9251) and ACTA network trials (43% of 227) proposed a health economic evaluation. In the subgroup analysis, 22% of the 324 acute care trials and 53% of the 38 ACTA network acute care trials proposed a health economic evaluation. Acute care trials funded by government bodies were significantly more likely to propose and publish a health economic evaluation than those funded by hospitals, universities, and other funders, after adjusting for phase, registration year, primary sponsor type, and comparator. Current uptake of health economic evaluations alongside Australian-led clinical trials is low, with uptake higher among the subset of ACTA network trials. This is despite economic evidence playing an increasingly prominent role in health system management, as well as rising health expenditure, limited budgets, and competing demands. There is significant opportunity to embed health economic evaluations alongside clinical trials, particularly phase 3 trials, to increase research outputs and optimize research translation. Investing in clinical trial networks that support funding for a health economist or a health economic evaluation may be an effective strategy to increase the uptake of health economic evaluations alongside trials.

Improvement in symptoms of anxiety and depression in individuals with type 2 diabetes: retrospective analysis of an intensive lifestyle modification program

BackgroundType 2 diabetes (T2D) is a chronic metabolic disorder that has a notable influence on mental well-being, contributing to elevated morbidity and mortality rates. Depression and anxiety disorders are the most common mental health concerns among patients with T2D worldwide. Therefore, the present study aimed to assess the impact of an online intensive lifestyle intervention (ILI) on mental health outcomes (depression and anxiety) in patients with T2D in India.Materials and methodsThis retrospective pre-post analysis included adult patients (aged > 18 years) diagnosed with T2D who were enrolled in a diabetes management program in India between June 2021 and June 2023. The intervention consisted of lifestyle modifications such as a customized plant-based diet, regular physical activity, psychological support through group and individual therapy, and medical management. Data were extracted from the electronic database of the clinic, including anthropometry, medical history, biochemical parameters, symptoms of depression, and anxiety (assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorders-7 (GAD-7) scale) at the start and end of the six-month intervention period.ResultsOf the 1061 eligible patients (177 with prediabetes), 40.3% were female. The mean age, duration of diabetes, and HbA1c levels were 52 ± 10.4 years, 9.8 ± 7.8 years, and 8 ± 1.7%, respectively. The prevalence of symptoms of depression and anxiety (ranging from mild to severe) was 46% and 44.3%, respectively, which reduced to 28.7% and 29.2%, respectively, post-intervention.ConclusionIntegrated ILI successfully improved the symptoms of anxiety and depression, highlighting the importance of a multidisciplinary approach that includes diet, physical activity, psychological support, and medical management in enhancing mental health outcomes among patients with T2D. Future prospective studies are needed to explore the long-term effects of such interventions and develop effective strategies for promoting mental health in diverse populations.Trial registrationThe study was approved by the Freedom from Diabetes Research Foundation Institutional Ethics Committee (approval number FFDRF/IEC/2024/7) and registered in the Clinical Trials Registry of India (CTRI/2024/03/064596, registered on March 21, 2024).

Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis

PurposeSteatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).Materials and methodsThe UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.ResultsOne hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.ConclusionUDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.Critical relevance statementUDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).Trial registrationThe research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.Key PointsThere is a lack of non-invasive quantitative measurement options for hepatic steatosis.UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.S8, end-expiratory, supine, and fasting may be the more stable measuring condition.Training could improve the operators’ measurement stability.Variable measurement state affects the repeatability of the UDFF values (Cov).Graphical

Assessing the reach and engagement of three anti-vaping messages on Facebook Targeting Australian Youth: a protocol for a randomised trial

BackgroundVaping among 18-24-year-old Australians has increased from 5.8% in 2019 to 21% in 2023. This protocol describes a trial to investigate the dissemination and engagement achieved by three anti-vaping messages on Facebook.MethodsThis research employs a 3-arm randomised experimental design. Three distinct anti-vaping messages will be disseminated via Facebook using Meta Ads Manager. Each arm has a message that focuses on either health risks, environmental impact, or anti-vape industry sentiment. The campaign will run for three months. The primary outcome is the engagement rate as a measure of the effectiveness of anti-vaping message, and the secondary outcomes include network indicators: size, density, centralisation, and centrality to evaluate the extent to which the messages are disseminated. Participants will be randomly exposed to one of the three messages. Data on reach and engagement will be compared across the groups.DiscussionThis study will provide insights into the dissemination of social media-based anti-vaping campaigns. By evaluating engagement rates and network indicators, the research aims to identify which message themes engage most with young Australians. The findings will contribute to the development of more effective public health strategies for vaping cessation and prevention among youth.Trial RegistrationThe study was registered on July 19th 2024 with the Australian New Zealand Clinical Trials Registry (ACTRN12624000885594).

The effects of screen-based simulation on nursing students’ acquisition of medication administration and dosage calculation skills: a randomized controlled trial

BackgroundScreen-based simulation is a cost-effective educational modality that allows nursing students to comfortably acquire new skills as they become accustomed to digital environments. The aim of this study is to evaluate the effectiveness of a screen-based simulation tool in enhancing knowledge and skills related to medication administration and dosage calculation in nursing students.MethodsThis multicenter, single-blind, stratified, randomized controlled trial initially enrolled 480 nursing students. The 351 students eligibles were randomly allocated to two groups. Using a screen-based simulation tool (SIMDOSE®), the intervention group was trained in drug administration and dosage calculation through four perfusion clinical cases. The control group underwent the same training content using the paper-and-pencil method. knowledge and skills acquisition, Students’ satisfaction, self-confidence and anxiety were analyzed using Jamovi software (version 2.3.18).Results4 out of 5 main variables examined were significantly different, specifically in dosage calculation, where the simulation group excelled both in the knowledge post-test (post – pre = 1.00 (20%); p = 0.004) and in the objective structured clinical examination (p = 0.013). The intervention group reported higher levels of satisfaction and self-confidence than the control group (p < 0.001). Their moderate anxiety levels didn’t differ significantly (0.161).ConclusionThe SIMDOSE® platform can be used as a supplementary teaching method of dosage calculation for nursing students. Screen-based simulation has benefits that nurse educators should be aware of, such as being a key to more satisfied and confident students.Trial registrationThis Moroccan clinical trial was prospectively registered (16/05/2023) in the Pan African Clinical Trial Registry (pactr.samrc.ac.za) with trial registration number PACTR202305505743210.

The effect of coaching on health information literacy in patients with chronic kidney disease: a randomized controlled trial

BackgroundSince chronic kidney disease is highly insidious in the early stages, most diagnosed patients have already developed irreversible renal failure. There is a lack of effective implementation and standardization of health education management for patients with chronic kidney disease, and the impact of health education management on health information literacy is not yet known.MethodsThis randomized controlled clinical trial was conducted from March 2022 to March 2023. A total of 130 patients with chronic kidney disease stage 3–4 were selected from a tertiary hospital in Zhuhai via a convenience sampling method and were then randomly assigned to intervention and control groups. The Health Information Literacy Questionnaire for Chronic Kidney Disease was used to assess the health literacy of the patients at month 0 and month 12. In addition, the renal function-related indices of the patients were measured before and after the intervention. The study adhered to SPIRIT guidelines.ResultsThere was no significant difference between the two groups in health information literacy, platelet count, estimated glomerular filtration rate, or albumin level. However, the intervention group showed a significant improvement in health behavioral status such as information acquisition, checkups, and physical activity. Subgroup analysis revealed that hemoglobin was significantly higher in non-employed patients than in the intervention group. There was a significant improvement in hemoglobin level after receiving health guidance in patients with intermediate education, and acquisition capacity and estimated glomerular filtration rate in the intervention group were lower than in the control group for patients with elementary education.ConclusionReceiving health coaching helped to improve self-management behaviors and hemoglobin levels of patients with stage 3–4 chronic kidney disease. Education level is an important factor influencing the effectiveness of health coaching techniques.Trial registrationThis study was prospectively registered in the China Clinical Trial Registry on November 10, 2021, with registration number: ChiCTR2100053103.

Evaluation of efficacy and safety of low-intensity pulsed ultrasound in patients with concurrent erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized controlled study

ObjectiveThe primary objective of this clinical trial is to investigate the effect of low-intensity pulsed ultrasound (LIPUS) on patients suffering from comorbid erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS).MethodsThe clinical trial was conducted in the andrology outpatient treatment room of the Department of Urology, Xiangya Hospital, Central South University from August to November 2022 A total of 60 patients who met the research criteria for comorbid ED combined with CP/CPPS were recruited and randomly assigned to three treatment groups. They were treated with LIPUS (Group A), drug therapy(Group B), and LIPUS combined with drug therapy (Group C), respectively. Each group comprised 20 patients. Statistical analysis was performed on the five-item version of International Index of Erectile Function (IIEF-5), Erection Hardness Score (EHS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the nine-item Patient Health Questionnaire (PHQ-9), the seven-item Generalized Anxiety Disorder Scale (GAD-7), and the incidence of adverse events to comprehensively evaluate the efficacy and safety of LIPUS.ResultsThe positive response rate of ED and CP/CPPS treatment in Group A is 40%(8/20) and 45%(9/20), while those in Group B is 55%(11/20) and 60%(12/20), and those in Group C is 85%(17/20) and 85%(17/20). A notable increase in IIEF-5 scores was observed across the three groups post-treatment (10.45 ± 2.50 vs. 13.65 ± 3.03, P = 0.008; 11.80 ± 3.21 vs. 16.40 ± 3.20, P = 0.011; 12.90 ± 3.92 vs. 19.40 ± 2.35, P = 0.042) with a concomitant significant decrease in NIH-CPSI scores (16.75 ± 4.53 vs. 14.65 ± 4.51, P = 0.016; 16.35 ± 4.32 vs. 12.20 ± 4.74, P = 0.007; 16.00 ± 4.40 vs. 8.15 ± 4.28, P = 0.021). Notably, the most pronounced changes were seen in the group receiving LIPUS combined with tadalafil and doxazosin. Additionally, all groups exhibited marked improvements in anxiety and depression symptoms post-treatment. No adverse events were observed during treatment.ConclusionLIPUS can improve erectile function and CP/CPPS symptoms with good safety, and LIPUS combined with tadalafil and doxazosin is more effective during the treatment. However, its long-term efficacy remains to be seen.Trial RegistrationChinese Clinical Trial Registry; approval number: ChiCTR2200063038 (https://www.chictr.org.cn/) on August 29, 2022.

Elritercept, a Modified Activin Receptor IIA Ligand Trap, increased Erythropoiesis and Thrombopoiesis in a Phase 1 Trial

The TGF-β superfamily plays a crucial role in regulating biological processes of virtually every tissue and system in the body, including hemostasis and hematopoiesis. Elritercept (KER-050) is an investigational, modified activin receptor type IIA ligand trap designed to bind and inhibit activin A and other select TGF-β superfamily ligands including activin B and growth differentiation factor (GDF)-8 and GDF-11. The objectives of this Phase 1 randomized, placebo-controlled study of elritercept were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamic markers of activin inhibition and hematopoiesis in healthy, post-menopausal women (N=48). This study was comprised of 2 parts: single ascending doses ranging from 0.05 to 4.5 mg/kg, and multiple (up to 2 doses) ascending doses of 0.75 mg/kg administered subcutaneously (SC) every 4 weeks. Elritercept was generally well-tolerated at all dose levels, with no dose limiting toxicities observed. There were no severe or serious adverse events nor clinically significant changes in safety laboratory measures. Serum concentrations increased in dose-proportional manner following single SC doses, with peak concentrations achieved in 4.5 to 6 days and a mean elimination half-life of 12 days. These parameters were comparable following multiple doses. Elritercept elicited rapid, sustained, and dose-dependent increases in reticulocytes, red blood cells, hemoglobin, and platelets without eliciting detrimental changes in white blood cells such as neutrophils and lymphocytes. The time course and duration of changes in these cell populations supported a differentiated pharmacologic profile that is consistent with stimulation of both early- and late-stage hematologic pathways. Australian New Zealand Clinical Trial Registry (ACTRN12619000318189).

Diagnostic Accuracy of Toluidine Blue Electrospun in Detecting Oral Potentially Malignant Disorders.

Oral potentially malignant disorders (OPMDs) with epithelial dysplasia can progress to oral squamous cell carcinoma (OSCC). Toluidine blue (TB) has been used in oral screening with various methods. This study aimed to evaluate the sensitivity and specificity of TB-containing electrospun fibers in detecting OPMDs with epithelial dysplasia compared to histopathology. The concentrations of polyvinylpyrrolidone (PVP) and TB were optimized for fiber diameter and puncture strength using the design of experiments method with a central composite design. These optimized fibers were tested on 36 suspected OPMD lesions in 30 patients, followed by a biopsy for histopathological examination. The quadratic and two-factor interaction models described the relationship between TB and PVP concentrations and fiber characteristics. The TB-containing electrospun fibers had 77.3% sensitivity and 35.7% specificity in detecting OPMDs with epithelial dysplasia. The TB-containing electrospun fibers offer advantages such as easy application, cost-effectiveness, and enhanced sensitivity in identifying OPMDs with epithelial dysplasia. However, their diagnostic accuracy is insufficient as a standalone diagnostic method, and they should be considered an adjunctive tool for detecting dysplastic changes in the oral epithelium. Thailand Clinical Trials Registry: TCTR20240429002.

The effect of combined pudendal nerve and spermatic cord block or caudal epidural block on postoperative analgesia after posterior urethroplasty: a randomized trial

BackgroundPostoperative pain management remains a significant challenge for patients undergoing posterior urethroplasty (PU). In a previous study, we proposed a novel technique of combined pudendal nerve (PN) and spermatic cord (SC) block to manage pain after PU. The present trial was conducted to test the hypothesis that this technique is effective for pain control after PU and provides longer-lasting analgesia than caudal epidural block (CB).MethodsSixty patients undergoing PU were randomized into two groups: Group NB received combined PN and SC block, and Group CB received CB. General anesthesia with a laryngeal mask was performed. The primary outcome was the postoperative analgesic duration, and the secondary outcomes included the Numeric Rating Scale (NRS) scores for pain and the number of patients with different motor scores of the lower limb at 3, 6, 12, and 24 h postoperatively.ResultsTwo patients in Group CB were withdrawn due to block failure. The postoperative analgesic duration was statistically longer in Group NB compared with Group CB (mean difference [95% confidence interval], 115.78 min [17.80, 213.75]; P = 0.021). The NRS scores for pain at 12 and 24 h after surgery were statistically lower in Group NB compared with Group CB. Group NB had statistically more patients with motor score 0 at 3 h postoperatively than Group CB.ConclusionsPN combined with SC block is an effective technique for postoperative analgesia in PU. This technique can achieve a longer duration of analgesia and lower pain scores, especially 12 h after surgery, than a CB.Trial registrationThis study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2100042971, registration date on 2/2/2021).

Shuxuening injection for treating acute ischemic stroke: a PRISMA-compliant systematic review and meta-analysis of randomized controlled trials

Background: Using Shuxuening injection (SXNI) for acute ischemic stroke (AIS) is popular in China, but its efficacy and safety remain controversial.Purpose: This study aims to assess the efficacy and safety of SXNI as an add-on therapy for AIS.Study design: Systematic review and meta-analysis.Methods: We searched for randomized controlled trials (RCTs) on SXNI for AIS in seven databases and two clinical trial registration platforms from their inception to January 2023. We used the Cochrane risk of bias tool to assess the methodological quality of the included studies and performed the meta-analysis with R software. The primary outcome was clinical efficacy, assessed by the clinical effective rate (CER). The secondary outcomes were neurological function, activities of daily living (ADL), and adverse events (AEs).Results: In total, 116 studies with 12,401 participants were included in this review. Fifteen (12.9%) studies were judged to be of moderate to high quality. SXNI plus conventional treatments (CTs) improved the CER compared with CTs alone (risk ratio [RR]: 1.21, 95% confidence interval [CI]: 1.17–1.25, p &amp;lt; 0.0001) or CTs plus other injections (RR: 1.18, 95% CI: 1.15–1.21, p &amp;lt; 0.0001). SXNI plus CTs reduced the National Institute of Health Stroke Scale score compared with CTs alone (mean difference [MD]: −4.00, 95% CI: −5.22 to −2.78, p &amp;lt; 0.0001) or CTs plus other injections (MD: −2.28, 95% CI: −3.41 to −1.16, p &amp;lt; 0.0001). SXNI plus CTs also decreased the Chinese Stroke Scale score compared with CTs alone (MD: −5.01, 95% CI: −7.38 to −2.65, p &amp;lt; 0.0001) or CTs plus other injections (MD: −4.31, 95% CI: −5.75 to −2.88, p &amp;lt; 0.0001). SXNI plus CTs was superior for increasing the Barthel index score compared with CTs alone (MD: 11.58, 95% CI: 8.27–14.90, p &amp;lt; 0.0001) or CTs plus other injections (MD: 5.43, 95% CI: 0.48–10.39, p = 0.0317). The level of evidence for each outcome was assessed as low to very low. The most common AEs of SXNI were cardiovascular system events, and all these AEs were mild.Conclusion: SXNI combined with CTs maybe better than CTs alone or CTs plus other injections for improving the clinical efficacy, neurological function, and ADL of AIS patients, with relatively reliable safety. However, due to the low quality of the included studies, more rigorously designed RCTs with large sample sizes should be conducted in the future.Systematic Review Registration:www.crd.york.ac.uk, identifier (CRD42023418565).