OBJECTIVE: To establish the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir (low or high dose) in children aged ≥ 28 days and ≤ 3 years with RSV disease.
METHODS: CROCuS was a multicenter, international, double-blind, placebo-controlled, randomized, adaptive phase II study, wherein children aged ≥ 28 days and ≤ 3 years with confirmed RSV infection who were either hospitalized (Cohort 1) or treated as outpatients (Cohort 2) were randomized (1:1:1) to receive rilematovir (low or high dose) or placebo. Study treatment was administered daily as an oral suspension from days 1 to 7, with dosing based on weight and age groups. The primary objective was to establish antiviral activity of rilematovir by evaluating the area under the plasma concentration-time curve of RSV viral load in nasal secretions from baseline through day 5. Severity and duration of RSV signs and symptoms and the safety and tolerability of rilematovir were also assessed through day 28 (± 3).
RESULTS: In total, 246 patients were randomized, treated, and included in the safety analysis population (Cohort 1: 147; Cohort 2: 99). Of these, 231 were included in the intent-to-treat-infected analysis population (Cohort 1: 138; Cohort 2: 93). In both cohorts, demographics were generally similar across treatment groups. In both cohorts combined, the difference (95% confidence interval) in the mean area under the plasma concentration-time curve of RSV RNA viral load through day 5 was - 1.25 (- 2.672, 0.164) and - 1.23 (- 2.679, 0.227) log10 copies∙days/mL for the rilematovir low-dose group and the rilematovir high-dose group, respectively, when compared with placebo. The estimated Kaplan-Meier median (95% confidence interval) time to resolution of key RSV symptoms in the rilematovir low-dose, rilematovir high-dose, and placebo groups of Cohort 1 was 6.01 (4.24, 7.25), 5.82 (4.03, 8.18), and 7.05 (5.34, 8.97) days, respectively; in Cohort 2, estimates were 6.45 (4.81, 9.70), 6.26 (5.41, 7.84), and 5.85 (3.90, 8.27) days, respectively. A similar incidence of adverse events was reported in patients treated with rilematovir and placebo in Cohort 1 (rilematovir: 61.9%; placebo: 58.0%) and Cohort 2 (rilematovir: 50.8%; placebo: 47.1%), with most reported as grade 1 or 2 and none leading to study discontinuation. The study was terminated prematurely, as the sponsor made a non-safety-related strategic decision to discontinue rilematovir development prior to full recruitment of Cohort 2.
CONCLUSIONS: Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need.
CLINICAL TRIAL REGISTRATION: EudraCT Number: 2016-003642-93; ClinicalTrials.gov Identifier: NCT03656510. First posted date: 4 September, 2018.
METHODS: Patients with symptomatic AF and moderate to severe MR who underwent catheter ablation from 2011 to 2021 were retrospectively included in the study. Patients' baseline characteristics and electrophysiological features were examined. These patients were classified as group 1 with improved MR and group 2 with refractory MR after CA.
RESULTS: Fifty patients (age 60.2 ± 11.6 years, 29 males) were included in the study (32 in group 1 and 18 in group 2). Group 1 patients had a lower CHA2DS2-VASc score (1.7 ± 1.5 vs. 2.7 ± 1.5, P = 0.005) and had a lower incidence of hypertension (28.1% vs. 66.7%, P = 0.007) and diabetes mellitus (3.1% vs. 22.2%, P = 0.031) as compared to group 2 patients. Electroanatomic three-dimensional (3D) mapping showed that group 1 patients demonstrated less scars on the posterior bottom of the left atrium compared to group 2 patients (12.5% vs. 66.7%, P
METHOD: Patient baseline characteristics and electrophysiological parameters were examined to identify the predictors of atrial fibrillation recurrence following catheter ablation. The clinical outcomes of catheter ablation and medical therapy were compared using the propensity score matched method.
RESULTS: A total of 343 patients were enrolled, with 46 in the catheter ablation group and 297 in the medical therapy group. Among the catheter ablation group, 58.7% (n = 27) had persistent atrial fibrillation. The recurrence rate of atrial arrhythmia was 30.4% (n = 14) after an average follow-up duration of 7.7 years following catheter ablation. The only predictive factor for atrial fibrillation recurrence after catheter ablation was the left atrial diameter. When compared to medical therapy, catheter ablation demonstrated significantly better outcomes in terms of overall survival, freedom from heart failure hospitalization, improvement in left ventricular ejection fraction, and a greater reduction in left ventricular diameter and left atrial diameter after propensity score matching.
CONCLUSIONS: Therefore, catheter ablation proves to be effective in providing long-term control of atrial fibrillation in patients with dilated cardiomyopathy. In addition to standard heart failure care, catheter ablation significantly enhanced both morbidity and mortality outcomes and reversed structural remodeling when compared to heart failure medication alone.
METHODS AND RESULTS: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence.
CONCLUSION: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.
OBJECTIVES: To assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures.
METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from pre-ablation pulmonary vein computed tomography. Patients were categorized based on the presence of LIPV triggers and/or drivers. Multivariate logistic regression was used to identify risk factors.
RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers and/or drivers. The Dao-LIPV distance had a better predictive performance (AUC: 0.70) compared to persistent AF (AUC: 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤ 2.5 mm (Odds ratio [OR] 3.96 [95% CI 2.15-7.29], p <0.001) and persistent AF (OR 1.73 [95% CI 1.02-2.94], p=0.044) were independent predictors for the presence of LIPV triggers and/or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤ 2.5mm (11.4%), and both (15.0%).
CONCLUSIONS: The close proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤ 2.5mm significantly increase the risk of LIPV triggers/drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.
METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.
RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p
STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries.
METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set.
RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior.
CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.
AIMS: The present study aimed to examine the fit of different measurement models for the AUDIT and its measurement invariance across a wide range of subgroups by country, language, gender, and sexual orientation.
METHODS: Responses concerning past-year alcohol use from the participants of the cross-sectional International Sex Survey were considered (N = 62,943; Mage: 32.73; SD = 12.59). Confirmatory factor analysis, as well as measurement invariance tests were performed for 21 countries, 14 languages, three genders, and four sexual-orientation subgroups that met the minimum sample size requirement for inclusion in these analyses.
RESULTS: A two-factor model with factors describing 'alcohol use' (items 1-3) and 'alcohol problems' (items 4-10) showed the best model fit across countries, languages, genders, and sexual orientations. For the former two, scalar and latent mean levels of invariance were reached considering different criteria. For gender and sexual orientation, a latent mean level of invariance was reached.
CONCLUSIONS: In line with the two-factor model, the calculation of separate alcohol-use and alcohol-problem scores is recommended when using the AUDIT. The high levels of measurement invariance achieved for the AUDIT support its use in cross-cultural research, capable also of meaningful comparisons among genders and sexual orientations.
METHOD: Using data from the International Sex Survey (N = 82,243; Mage = 32.39 years, SD = 12.52), we evaluated the psychometric properties of the CSBD-19 and CSBD-7 and compared CSBD across 42 countries, three genders, eight sexual orientations, and individuals with low vs. high risk of experiencing CSBD.
RESULTS: A total of 4.8% of the participants were at high risk of experiencing CSBD. Country- and gender-based differences were observed, while no sexual-orientation-based differences were present in CSBD levels. Only 14% of individuals with CSBD have ever sought treatment for this disorder, with an additional 33% not having sought treatment because of various reasons. Both versions of the scale demonstrated excellent validity and reliability.
DISCUSSION AND CONCLUSIONS: This study contributes to a better understanding of CSBD in underrepresented and underserved populations and facilitates its identification in diverse populations by providing freely accessible ICD-11-based screening tools in 26 languages. The findings may also serve as a crucial building block to stimulate research into evidence-based, culturally sensitive prevention and intervention strategies for CSBD that are currently missing from the literature.
METHODS: Using data from the International Sex Survey (N = 82,243; Mage = 32.39; SDage = 12.52; women: n = 46,874; 57 %), we examined the reliability of depression and anxiety symptom scores of the BSI-18, as well as evaluated evidence of construct, invariance, and criterion-related validity in predicting clinically relevant variables across countries, languages, genders, and sexual orientations.
RESULTS: Results corroborated an invariant, two-factor structure across all groups tested, exhibiting excellent reliability estimates for both subscales. The 'caseness' criterion effectively discriminated among those at low and high risk of depression and anxiety, yielding differential effects on the clinical criteria examined.
LIMITATIONS: The predictive validation was not made against a clinical diagnosis, and the full BSI-18 scale was not examined (excluding the somatization sub-dimension), limiting the validation scope of the BSI-18. Finally, the study was conducted online, mainly by advertisements through social media, ultimately skewing our sample towards women, younger, and highly educated populations.
CONCLUSIONS: The results support that the BSI-12 is a valid and reliable assessment tool for assessing depression and anxiety symptoms across countries, languages, genders, and sexual orientations. Further, its caseness criterion can discriminate well between participants at high and low risk of depression and anxiety.
METHODS: We used global survey data from 82,243 individuals (Mean age=32.39 years; 40.3 % men, 57.0 % women, 2.8 % non-binary, and 0.6 % other genders) participating in the International Sexual Survey (ISS; https://internationalsexsurvey.org/) across 42 countries and 26 languages. Participants completed the SDS-3, as well as questions regarding sociodemographic characteristics, including gender identity and sexual orientation.
RESULTS: Confirmatory factor analysis (CFA) supported a unidimensional factor structure for the SDS-3, and multi-group CFA (MGCFA) suggested that this factor structure was invariant across countries, languages, gender identities, and sexual orientations. Cronbach's α for the unidimensional score was 0.83 (range between 0.76 and 0.89), and McDonald's ω was 0.84 (range between 0.76 and 0.90). Participants who did not experience sexual problems had significantly lower SDS-3 total scores (M = 2.99; SD=2.54) compared to those who reported sexual problems (M = 5.60; SD=3.00), with a large effect size (Cohen's d = 1.01 [95 % CI=-1.03, -0.98]; p < 0.001).
CONCLUSION: The SDS-3 has a unidimensional factor structure and appears to be valid and reliable for measuring sexual distress among individuals from different countries, gender identities, and sexual orientations.
METHOD: Our analysis is based on a large-scale research project involving 42 countries (International Sex Survey, N=72,627, 57% women, Mage=32.84; SDage=12.57).
RESULTS: The ASRS Screener demonstrated good reliability and validity, along with partial invariance across different languages, countries, and genders. The occurrence of being at risk for adult ADHD was relatively high (21.4% for women, 18.1% for men). The highest scores were obtained in the US, Canada, and other English-speaking Western countries, with significantly lower scores among East Asian and non-English-speaking European countries. Moreover, ADHD symptom severity and occurrence were especially high among gender-diverse individuals. Significant associations between adult ADHD symptoms and age, mental and sexual health, and socioeconomic status were observed.
CONCLUSIONS: Present results show significant cross-cultural variability in adult ADHD occurrence as well as highlight important factors related to adult ADHD. Moreover, the importance of further research on adult ADHD in previously understudied populations (non-Western countries) and minority groups (gender-diverse individuals) is stressed. Lastly, the present analysis is consistent with previous evidence showing low specificity of adult ADHD screening instruments and contributes to the current discussion on accurate adult ADHD screening and diagnosis.