Assessment of the Utility of Physiologically-based Pharmacokinetic Model for prediction of Pharmacokinetics in Chinese and Japanese Populations.

The objective for the present analyses was to evaluate the utility of physiologically-based pharmacokinetic (PBPK) modeling for prediction of the pharmacokinetics (PK) in Chinese and Japanese populations with a panel of Pfizer internal compounds. Twelve compounds from Pfizer internal development pipeline with available Westerner PK data and available PK data in at least one of the subpopulations of Japanese and Chinese populations were identified and included in the current analysis. These selected compounds represent various elimination pathways across different therapeutic areas. The Simcyp® PBPK simulator was used to develop and verify the PBPK models of individual compounds. The developed models for these compounds were verified by using the clinical PK data in Westerners. The verified PBPK models were further used to predict the PK of these compounds in Chinese and Japanese populations and the predicted PK parameters were compared with the observed PK parameters. Ten of the 12 compounds had PK data in Chinese, and all the 12 compounds had PK data in Japanese. In general, the PBPK models performed well in predicting PK in Chinese and Japanese, with 8 of 10 drugs in Chinese and 7 of 12 drugs in Japanese has AAFE values less than 1.25-fold. PBPK-guided predictions of the relative PK difference were successful for 75% and 50%, respectively, between Chinese and Western and between Japanese and Western of the tested drugs using 0.8-1.25 as criteria. In conclusion, well verified PBPK models developed using data from Westerners can be used to predict the PK in Chinese and Japanese populations.

Feeling Unsafe at School and Associated Mental Health Difficulties among Children and Adolescents: A Systematic Review.

This study systematically reviewed the literature on perceived school safety. We investigated the prevalence, factors and associated mental health difficulties, as well as cross-cultural findings. Five databases were searched up to 9 February 2021 for peer-reviewed papers published in English. We included quantitative studies that explored the perception of school safety among children and adolescents. The reference lists of the selected papers were also searched. We conducted a narrative synthesis of the included studies. The review included 43 papers. The mean prevalence of the students who felt unsafe at school was 19.4% and ranged from 6.1% to 69.1%. Their perceived safety was associated with a wide range of personal, school, and social factors. Not feeling safe at school was related to being victimized and mental health difficulties, including depressive symptoms and suicidal behavior. Higher perceived school safety was associated with measures such as the presence of a security officer and fair school rule enforcement. The results showed the lack of cross-cultural studies on perceived school safety. Empirical studies are needed that examine the mechanisms of school safety, using valid measures. A clear definition of school safety should be considered a key aspect of future studies.