Aim: We evaluated healthcare practitioners’ perspectives regarding clinical pharmacogenetics in Cairo, Egypt. Materials & methods: We administered a paper-based survey to pharmacists and physicians practicing at Children’s Cancer Hospital Egypt. The survey assessed practitioners’ knowledge, attitudes, and perspectives about pharmacogenetic testing. Results: The study included 184 respondents (67.9% pharmacists; 32.1% physicians. Overall, the pharmacogenetic knowledge was low (mean = 41.7%) but attitudes toward pharmacogenetic testing and its potential clinical application were generally positive. Pharmacists responded more favorably than physicians to statements attributing the responsibility of applying pharmacogenetics in the clinical setting to their profession. However, several challenges were identified; the most common being: lack of pharmacogenetic knowledge and skill, lack of pharmacogenetic testing devices, and limited funding. Conclusion: Future efforts to promote pharmacogenetic implementation should focus on foundational education, practical training, and exploration of potential funding sources.

Background: Setting health-protective standards for poly- and perfluoroalkyl substances (PFAS) exposure requires estimates of their population toxicokinetics, but existing studies have reported widely varying PFAS half-lives (T ½ ) and volumes of distribution (V d ). Objectives: We combined data from multiple studies to develop harmonized estimates of T ½ and V d , along with their interindividual variability, for four PFAS commonly found in drinking water: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). Methods: We identified published data on PFAS concentrations in human serum with corresponding drinking water measurements, separated into training and testing data sets. We fit training data sets to a one-compartment model incorporating interindividual variability, time-dependent drinking water concentrations, and background exposures. Use of a hierarchical Bayesian approach allowed us to incorporate informative priors at the population level, as well as at the study level. We compared posterior predictions to testing data sets to evaluate model performance. Results: Posterior median (95% CI) estimates of T ½ (in years) for the population geometric mean were 3.14 (2.69, 3.73) for PFOA, 3.36 (2.52, 4.42) for PFOS, 2.35 (1.65, 3.16) for PFNA, and 8.30 (5.38, 13.5) for PFHxS, all of which were within the range of previously published values. The extensive individual-level data for PFOA allowed accurate estimation of population variability, with a population geometric standard deviation of 1.57 (95% CI: 1.42, 1.73); data from other PFAS were also consistent with this degree of population variability. V d estimates ranged from 0.19 to across the four PFAS, which tended to be slightly higher than previously published estimates. Discussion: These results have direct application in both risk assessment (quantitative interspecies extrapolation and uncertainty factors for interindividual variability) and risk communication (interpretation of monitoring data). In addition, this study provides a rigorous methodology for further refinement with additional data, as well as application to other PFAS. https://doi.org/10.1289/EHP10103

BACKGROUND: Lead (Pb) is a highly toxic pollutant. Evidence suggests it is associated with cardiovascular disease (CVD)-related mortality. OBJECTIVES: We present a rigorous approach for identifying concentration-response functions that relate adult Pb exposures to CVD mortality to inform a health impact model (HIM). We then use the model in a proof-of-concept example. METHODS: Building on previously conducted government literature reviews and a de novo supplemental literature review, we compiled and evaluated the available data on Pb and CVD mortality in humans. We applied a set of predefined selection criteria to identify studies that would be most useful in understanding the impact of Pb exposure on CVD mortality risk in adults. Once we identified the studies, we derived a HIM and used each study's concentration-response function in a proof-of-concept example. RESULTS: Our literature search identified 15 studies for full-text review. Of those 15 studies, 4 fit our criteria for use in the HIM. Using population and CVD mortality rates for 40-to 80-y-olds in 2014, we estimated that 34,000-99,000 deaths have been avoided due to the lowering of blood Pb levels from 1999 to 2014. Based on these values we estimated that approximately 16%-46% of the decreased CVD-related death rate from 1999 to 2014 may be attributable to decreased blood Pb levels. CONCLUSION: Our results demonstrate that decreases in Pb exposure can result in large benefits for the adult population. We have provided a HIM that can be used in a variety of applications from burden-of-disease estimates to regulatory impact assessments and have demonstrated its sensitivity to the choice of concentration-response function.