Perspectives of French adolescents with ADHD and child and adolescent psychiatrists regarding methylphenidate use.

Many studies have demonstrated the short-term efficacy and tolerability of methylphenidate treatment adolescents with attention deficit hyperactivity disorder (ADHD). Qualitative literature on this matter focused on school outcomes, long-term side effects, family conflicts, personality changes and stigmatization. Yet, no qualitative study has crossed the perspectives of child and adolescent psychiatrists (CAPs) prescribing methylphenidate and adolescents with ADHD. This French qualitative study followed the five stages IPSE-Inductive Process to analyze the Structure of lived Experience-approach. Fifteen adolescents with ADHD and 11 CAPs were interviewed. Data collection by purposive sampling continued until data saturation was reached. Data analysis, based on a descriptive and structuring procedure to determine the structure of lived experience characterized by the central axes of experience, produced two axes: (1) The process of methylphenidate prescription, highlighting how this prescription was motivated from the exterior, experienced as passive by the adolescents and required commitment from the CAPs; and (2) the perceived effects of methylphenidate treatment, in three domains: at school, in relationships and in the sense of self. Findings raised both the issues of the epistemic position and social representation of the adolescents about ADHD and methylphenidate within this specific French context, and the self-awareness and perception of the adolescents with ADHD. We conclude that these two issues need to be regularly addressed by the CAPs prescribing methylphenidate to avoid epistemic injustice and prevent the harmful effects of stigmatization.

Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation.

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8-45.6 M-1 and enthalpy change values up to -4 kJ·M-1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.

Spontaneously Hypertensive Rat substrains show differences in model traits for addiction risk and cocaine self-administration: Implications for a novel rat reduced complexity cross.

Forward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine self-administration traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated model traits for cocaine addiction risk and cocaine self-administration behaviors using a longitudinal within-subjects design. Impulsive-like and compulsive-like traits were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine use studied under fixed-ratio and tandem schedules of cocaine self-administration. Compulsive-like behavior correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the tandem schedule. Compulsive-like behavior also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22 %-40 % of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.