Background: Many children and adolescents experience violent events which can be associated with negative consequences for their development, mental health, school, and social functioning. However,... Show moreBackground: Many children and adolescents experience violent events which can be associated with negative consequences for their development, mental health, school, and social functioning. However, findings between settings and on the role of gender have been inconsistent. This study aimed to investigate cross-country and gender differences in the relationship between community violence exposure (CVE) and school functioning in a sample of youths from three countries. Methods: A self-report survey was conducted among school students (12-17 years old) in Belgium (Antwerp, N = 4,743), Russia (Arkhangelsk, N = 2,823), and the US (New Haven, N = 4,101). Students were recruited from within classes that were randomly selected from within schools that had themselves been randomly selected (excepting New Haven, where all students were included). CVE was assessed with the Screening Survey of Exposure to Community Violence. School functioning was assessed with four measures: the Perceived Teacher Support scale, Negative Classroom Environment scale, and Academic Motivation and Perception of Safety at School scales. Multivariate Analyses of Covariance were performed to assess differences in the levels of school-related problem behaviors in boys and girls, who reported different degrees of CVE. Results: Participants in all three countries reported a relatively high prevalence of violence exposure (36.2% in Belgium, 39.3% in Russia and 45.2% in the US who witnessed violence), with a higher proportion of girls than boys witnessing violent events (varied from 37.4 to 51.6% between the countries), whereas boys reported more episodes of victimization by violence than girls (varied from 32.3 to 49.9% between the countries). Youths who experienced increased CVE (from no exposure to witnessing to victimization) reported an increase in all school functioning problems in all of the countries and this association was not gender-specific. Conclusions: Our findings suggest that regardless of differences in the level of CVE by country and gender, violence exposure is negatively associated with school functioning across countries. Nonetheless, even though reactions to community violence among adolescents may be expressed in a similar fashion, cross-country differences in social support systems should also be taken into account in order to provide culturally sensitive treatment modalities. Show less
Daele, R. van; Debaveye, Y.; Vos, R.; Bleyenbergh, P. van; Bruggemann, R.J.; Dreesen, E.; ... ; Spriet, I. 2021
Background Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been... Show moreBackground Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin.Objectives We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype.Patients We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations.Results These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction.Conclusions CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles. Show less
Lanzoni, A.; Castoldi, A.F.; Kass, G.E.N.; Terron, A.; Seze, G. de; Bal-Price, A.; ... ; Younes, M. 2019
The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has... Show moreThe apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this “declining effect”. We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Show less
