In silico toxicology protocols

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information

Evaluation of an institution-wide guideline for hyperglycemic emergencies at a tertiary academic medical center

BACKGROUND: No previous studies exist examining implementation of an institution-wide guideline and order set for hyperglycemic emergencies (diabetic ketoacidosis [DKA] and hyperosmolar hyperglycemic state [HHS]). OBJECTIVE: Evaluate the impact of an institutional guideline and order set for hyperglycemic emergencies. METHODS: This retrospective descriptive study evaluated patients with a diagnosis of DKA or HHS. Two time periods were evaluated: phase 1 (PRE) assessed practice preguideline implementation, and phase 2 (POST) assessed practice postguideline and order set introduction. RESULTS: A total of 172 patients (91 PRE and 81 POST) were included in the analysis. There was no difference in the mean hospital length of stay (LOS) in the PRE versus POST groups (5.2 +/- 4 vs 5.9 +/- 8.6 days, P = .49). The mean intensive care unit (ICU) LOS was shorter in the POST group (64.8 +/- 19 vs 37.1 +/- 74.8 hours, P \u3c .01). The POST group had an increase in frequency of assessments for clearance of urinary ketones (18 vs 33.3%, P = .03) and beta-hydroxybutyrate (16 vs 37%, P \u3c .01). Frequency of point-of-care glucose testing (12.5 +/- 4.6 vs 15.1 +/- 4.7, P \u3c .01) and time to anion gap closure (13 +/- 9 vs 9.3 +/- 7.4 hours, P \u3c .01) improved in the POST group. There was no difference in the number of patients experiencing hypoglycemia or hypokalemia between both groups. CONCLUSIONS: Implementation of an institutional guideline and order set for hyperglycemic emergencies decreased ICU LOS and time to anion gap closure, with no difference in rates of hypoglycemia