Dioxins vs. PFAS: Science and Policy Challenges.

BACKGROUND: Dioxin-like chemicals are a group of ubiquitous environmental toxicants that received intense attention in the last two decades of the 20th century. Through extensive mechanistic research and validation, the global community has agreed upon a regulatory strategy for these chemicals that centers on their common additive activation of a single receptor. Applying these regulations has led to decreased exposure in most populations studied. As dioxin-like chemicals moved out of the limelight, research and media attention has turned to other concerning contaminants, including per- and polyfluoroalkyl substances (PFAS). During the 20th century, PFAS were also being quietly emitted into the environment, but only in the last 20 years have we realized the serious threat they pose to health. There is active debate about how to appropriately classify and regulate the thousands of known PFAS and finding a solution for these "forever chemicals" is of the utmost urgency. OBJECTIVES: Here, we compare important features of dioxin-like chemicals and PFAS, including the history, mechanism of action, and effective upstream regulatory strategies, with the objective of gleaning insight from the past to improve strategies for addressing PFAS. DISCUSSION: The differences between these two chemical classes means that regulatory strategies for dioxin-like chemicals will not be appropriate for PFAS. PFAS exert toxicity by both receptor-based and nonreceptor-based mechanisms, which complicates mixtures evaluation and stymies efforts to develop inexpensive assays that accurately capture toxicity. Furthermore, dioxin-like chemicals were unwanted byproducts, but PFAS are useful and valuable, which has led to intense resistance against efforts to restrict their production. Nonetheless, useful lessons can be drawn from dioxin-like chemicals and applied to PFAS, including eliminating nonessential production of new PFAS and proactive investment in environmental remediation to address their extraordinarily long environmental persistence. https://doi.org/10.1289/EHP14449.

New Thrombotic Events in Ischemic Stroke Patients with Elevated Factor VIII.

Background. Heightened levels of Factor VIII (FVIII) have been associated with both arterial and venous thrombosis. While elevated FVIII is common during acute ischemic stroke (AIS), whether elevated FVIII confers an increased risk for recurrent thrombotic events (RTEs) following AIS has not been previously explored. Methods. Consecutive AIS patients who presented to our center between July 2008 and September 2013 and had FVIII measured during admission were identified from our stroke registry. Baseline characteristics and the occurrence of RTE (recurrent or progressive ischemic stroke, DVT/PE, and MI) were compared in patients with and without elevated FVIII levels. Results. Of the 298 patients included, 203 (68.1%) had elevated FVIII levels. Patients with elevated FVIII had higher rates of any in-hospital RTE (18.7% versus 8.4%, P = 0.0218). This association remained after adjustment for baseline stroke severity and etiology (OR 1.01, 95% CI 1.00-1.01, P = 0.0013). Rates of major disability were also higher in patients who experienced a RTE (17.8% versus 3.2%, P < 0.0001). Conclusion. A significantly higher frequency of in-hospital RTEs occurred in AIS patients with elevated FVIII. The occurrence of such events was associated with higher morbidity. Further study is indicated to evaluate whether FVIII is a candidate biomarker for increased risk of RTEs following AIS.

A comprehensive stroke center patient registry: advantages, limitations, and lessons learned.

INTRODUCTION: The use of a medical data registry allows institutions to effectively manage information for many different investigations related to the registry, as well as evaluate patient's trends over time, with the ultimate goal of recognizing trends that may improve outcomes in a particular patient population. METHODS: The purpose of this article is to illustrate our experience with a stroke patient registry at a comprehensive stroke center and highlight advantages, disadvantages, and lessons learned in the process of designing, implementing, and maintaining a stroke registry. We detail the process of stroke registry methodology, common data element (CDE) definitions, the generation of manuscripts from a registry, and the limitations. ADVANTAGES: The largest advantage of a registry is the ability to prospectively add patients, while allowing investigators to go back and collect information retrospectively if needed. The continuous addition of new patients increases the sample size of studies from year to year, and it also allows reflection on clinical practices from previous years and the ability to investigate trends in patient management over time. LIMITATIONS: The greatest limitation in this registry pertains to our single-entry technique where multiple sites of data entry and transfer may generate errors within the registry. LESSONS LEARNED: To reduce the potential for errors and maximize the accuracy and efficiency of the registry, we invest significant time in training competent registry users and project leaders. With effective training and transition of leadership positions, which are continuous and evolving processes, we have attempted to optimize our clinical research registry for knowledge gain and quality improvement at our center.