New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
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From Narcis.nl :" Patients with substance use disorder (SUD) are frequently suffering from co-occurring somatic disorders, increasing the risk of mortality. Somatic health care utilization (sHCU) often remains unknown to the physician during SUD treatment. This paper analyses sHCU and associated costs among patients in SUD treatment compared to matched, non-substance dependent controls. METHODS: Health care utilization data on 4972 SUD patients were matched to 19,846 controls by gender, birth year and ethnic origin. Subcategories of patients were formed based on SUD and on co-morbid psychiatric disorder. Data on sHCU during the year prior to the last treatment contact (the 'index date') for both patients and their matched controls were extracted from a health insurance database. RESULTS: Patients had a higher sHCU (with increased associated costs) than controls, especially when alcohol dependence was involved. In particular, sHCU for cardiovascular, respiratory, infectious diseases, injuries and accidents was increased among patients. However, the use of preventive medication, such as lipid-lowering drugs, is lower among SUD patients. Co-morbidity of psychiatric disorders led to further increase of sHCU, whereas patients with comorbid non-affective psychotic disorder (NAPD) showed lower sHCU and costs. CONCLUSION: Patients with SUD overall have a high sHCU, associated with high costs. There are indications that SUD patients have less access to preventive medication. Patients with comorbid NAPD are at risk of possible underutilization of somatic health care. Furthermore, we conclude that these larger administrative databases allow for comparisons between various diagnostic categories."
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In Antenne Amsterdam wordt sinds 1993 jaarlijks het gebruik vanalcohol, tabak, cannabis en andere drugs in de hoofdstad in kaartgebracht. Dit gebeurt op basis van een combinatie van kwalitatieveen kwantitatieve methoden. In 2022 verzamelden we informatie via(1) interviews met een 24-koppig uitgaanspanel die vanuit insidersperspectief of vanuit hun rol als locatiemanager, organisator ofsecurity vertellen over het trendsettende uitgaansleven; (2) interviewsmet een panel kwetsbare jeugd waarin zes professionals zijnvertegenwoordigd die met buurtjongeren werken; (3) een anoniemesurvey (vragenlijsten) over middelengebruik bij 246 club- enfestivalbezoekers; en (4) analyse van testuitslagen van vijfduizendvrijwillig aangeleverde drugsmonsters bij de Amsterdamse testservices.Hoewel het jaar nog van start ging in een lockdown, werden demaatregelen in de loop van januari al versoepeld en in februarigrotendeels afgeschaft. Na twee zomers zonder festivals, draait hetgehele uitgaansleven in 2022 weer op volle toeren. Dit rapport schetstvanuit verschillende bronnen wat dat betekende voor gebruikspatronen en trends in de Amsterdamse wereld van genotmiddelen.Een wereld waarin alcohol alom aanwezig is, maar rokers in deminderheid raken. En waarin ecstasy weer favoriet is, maar nietiedereen feest met drugs.
