Skin sensitization in silico protocol

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship of skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization

Impact of interactive voice response technology on primary adherence to bisphosphonate therapy: a randomized controlled trial

Summary: Osteoporosis (weak bones) is a disorder that has high morbidity, mortality, and healthcare utilization. Effective treatment is available for this disorder, but many patients choose not to start therapy. This is the first study showing an intervention that increases the initiation rates to medications for osteoporosis. Introduction: One out of six patients prescribed an oral bisphosphonate does not initiate therapy, a phenomenon known as primary non-adherence. Reasons for bisphosphonate primary non-adherence have been identified, but not interventions that positively impact primary adherence rates. The purpose of this study is to determine the effectiveness of interactive voice response technology to improve oral bisphosphonate primary adherence. Methods: This was a prospective, randomized controlled trial conducted in January–December 2014 at Kaiser Permanente Colorado, an integrated healthcare system. Adults with a new oral bisphosphonate prescription for osteoporosis or osteopenia which was not purchased within 14–20 days of being ordered were included. There were 127 and 118 patients in the intervention group and control groups, respectively. The intervention group received an interactive voice response phone call followed by a letter 1 week later if primary non-adherence continued, whereas the control group did not receive any outreach. The primary outcome was the proportion of patients who purchased their oral bisphosphonate within 25 days of randomization. Results: There were 62/127 (48.8 %) intervention patients and 36/118 (30.5 %) control patients who purchased their bisphosphonate prescription within 25 days of randomization (OR = 2.17, 95 % CI 1.29–3.67). When adjusted for age, sex, history of bone mineral density scan and fracture, the odds ratio for intervention versus control group was 2.3 (95 % CI 1.34–3.94). Conclusion: An interactive voice response phone call and follow-up letter significantly improved primary adherence to oral bisphosphonate therapy. Such an intervention could be considered for improving primary adherence rates to other medication classes

Opioid use for pain management after implementation of a medicaid short-acting opioid quantity limit

BACKGROUND: The United States is currently experiencing an opioid abuse epidemic. Many policies and programs have been implemented at local, state, and national levels in an attempt to decrease prescription opioid addiction and overdose. On August 1, 2014, Colorado Medicaid implemented a policy change that limited the quantity of short-acting opioids (SAOs) that could be filled through the Medicaid benefit to no more than 4 tablets per day, or 120 tablets in 30 days. OBJECTIVE: To compare mean total daily dose (TDD) of opioids purchased by Kaiser Permanente Colorado (KPCO) Medicaid patients before and after implementation of the Medicaid SAO quantity limit. METHODS: This investigation used a pre/post study design to compare opioid use in Medicaid-eligible patients during the 90 days before implementation of the Medicaid quantity limit on August 1, 2014, and 90 days after full implementation of the change on December 31, 2014. The study was conducted at KPCO, an integrated care delivery system providing medical care for approximately 615,000 patients, of which over 54,000 are Medicaid members. Electronic medical and pharmacy records were used to identify patients and assess medication use. RESULTS: There was a small difference in opioid use in the population of Medicaid opioid users as evidenced by the median TDD of oral morphine equivalents (OME) purchased decreasing from 6.8 mg (IQR = 2.2-25.8) in the pre-implementation period to 6.6 mg (IQR = 1.7-24.0) in the postimplementation period (P = 0.027). The proportion of patients purchasing more than 120 mg OME per day and the proportion of patients purchasing long-acting opioids (LAOs) did not change significantly from the pre- to postimplementation period (OME \u3e 120 of 4.2% vs. 3.6%, respectively, P = 0.290; LAO use of 12.9% vs. 13.6%, respectively, P = 0.465). CONCLUSIONS: This study found a statistically significant 3% decrease of 0.2 mg OME per day in the primary study population. A 24% reduction of 10 mg OME per day before and after implementation of the Medicaid SAO quantity limit was found in those patients identified as exceeding the Medicaid SAO quantity limit at baseline. These patients tended to be purchasing low to moderate total daily doses of opioids at baseline

Polystyrene–Poly(ethylene oxide) Diblock Copolymer: The Effect of Polystyrene and Spreading Concentration at the Air/Water Interface

Polystyrene-<i>block</i>-poly­(ethylene oxide) (PS-PEO) is an amphiphilic diblock copolymer that undergoes microphase separation when spread at the air/water interface, forming nanosized domains. In this study, we investigate the impact of PS by examining a series of PS-PEO samples containing constant PEO (∼17 000 g·mol^–1) and variable PS (from 3600 to 200 000 g·mol^–1) through isothermal characterization and atomic force microscopy (AFM). The polymers separated into two categories: predominantly hydrophobic and predominantly hydrophilic with a weight percent of PEO of ∼20% providing the boundary between the two. AFM results indicated that predominantly hydrophilic PS-PEO forms dots while more hydrophobic samples yield a mixture of dots and spaghetti with continent-like structures appearing at ∼7% PEO or less. These structures reflect a blend of polymer spreading, entanglement, and vitrification as the solvent evaporates. Changing the spreading concentration provides insight into this process with higher concentrations representing earlier kinetic stages and lower concentrations demonstrating later ones. Comparison of isothermal results and AFM analysis shows how polymer behavior at the air/water interface correlates with the observed nanostructures. Understanding the impact of polymer composition and spreading concentration is significant in leading to greater control over the nanostructures obtained through PS-PEO self-assembly and their eventual application as polymer templates