Use of Predictive Analytics to Identify Unhealthy Opioid Use and Guide Intervention.

OBJECTIVE: The authors aimed to use the newly developed Opioid Risk Stratification Tool to identify individuals who may be at risk for unhealthy opioid use and to examine the impact of applying a mailing and engagement intervention to this population and their prescribers, with the goal of reducing high-risk prescribing behaviors, opioid medication use, and mortality rates. METHODS: A nonrandomized controlled study was conducted with members from two Medicaid managed care organizations. In both the intervention (N=131) and control (N=187) groups, an algorithm identified members at moderate to high risk for hazardous opioid use. Members at increased risk in the intervention group and their prescribers received a letter from the managed care organization, and members still at risk 3 months after the mailing were contacted by a care coordinator. Individuals in the control group were not contacted. Medicaid claims data were used to compare opioid use and prescribing practices between groups before and after the intervention. RESULTS: Individuals in the intervention group were less likely to have any opioid prescription postintervention compared with those in the control group (OR=0.55, p<0.001), and the intervention group had a greater reduction in the number of individuals with concurrent opioid and benzodiazepine prescriptions (OR=0.49, p=0.042). Practices such as multiple opioid prescriptions and multiple prescribers of opioids were not affected by the intervention. CONCLUSIONS: An intervention targeting individuals at risk for hazardous opioid use was associated with a reduction in some high-risk prescribing practices. Future research should determine the ideal mix of interventions to reduce as many risk factors as possible.

Developing Nursing Care Guidelines for Patients With COVID-19.

The COVID-19 pandemic has produced an abundance of new and evolving evidence related to providing care for this complex patient population. Keeping up with the rapid flow of published information can be challenging and time-consuming, even for those skilled at interpreting the literature. To help clinical nurses readily apply standardized, evidence-based recommendations in a rapidly changing healthcare environment, the Good Samaritan Medical Center Education Team created a nursing-specific guideline for care of patients with COVID-19.

Responsiveness and Convergent Validity of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

BACKGROUND: The CRS-PRO is a new patient-reported outcome measure (PROM) for chronic rhinosinusitis (CRS) that was developed using extensive patient input per Food and Drug Administration guidance on PROMs acceptable for use as end points in clinical trials. OBJECTIVE: To assess the responsiveness and convergent validity of the CRS-PRO following standard-of-care medical therapy. METHODS: This was a prospective study of 51 patients (21 with nasal polyps and 30 without) with newly diagnosed CRS or having an acute CRS exacerbation who were initiated on appropriate medical therapy. At the baseline visit each patient completed the CRS-PRO questionnaire, the 22-item Sino-Nasal Outcome Test, the EuroQol 5-dimensional questionnaire, and 4 Patient-Reported Outcome Measure Information System short forms along with objective testing including endoscopic and radiographic scores, smell discrimination, and nasal inspiratory flow testing. This same battery of questionnaires and testing was administered at a follow-up visit 4 to 8 weeks later. RESULTS: We verified that shortening the 21-item CRS-PRO to 12 items as previously described maintains its psychometric properties. The 12-item CRS-PRO was responsive with a large effect size (Cohen's d, 0.94) comparable to the longer 22-item Sino-Nasal Outcome Test (Cohen's d, 0.93). The instrument was slightly more responsive to medically treated patients with CRS without nasal polyps compared with patients with CRS with nasal polyps (Cohen's d, 1.1 vs 0.89, respectively). The change in 12-item CRS-PRO total score has moderate correlation with change in Lund-Mackay computed tomography scores. CONCLUSIONS: The CRS-PRO is a 12-item rigorously developed, responsive, and valid PROM that was developed using extensive input from patients with current definitions of CRS, including its 2 major phenotypes.

Development and Preliminary Validation of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

BACKGROUND: Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS. OBJECTIVE: This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS. METHODS: Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later. RESULTS: After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P < .0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P < .0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP. CONCLUSION: The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.

MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 µg/L in public water supplies and the WHO has recommended an upper limit of 10 µg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies.

A consumption-based GHG inventory for the U.S. state of Oregon.

Many U.S. states conduct greenhouse gas (GHG) inventories to inform their climate change planning efforts. These inventories usually follow a production-based method adapted from the Intergovernmental Panel on Climate Change. States could also take a consumption-based perspective, however, and estimate all emissions released to support consumption in their state, regardless of where the emissions occur. In what may be the first such comprehensive inventory conducted for a U.S. state, we find that consumption-based emissions for Oregon are 47% higher than those released in-state. This finding implies that Oregon's contribution to global greenhouse gas emissions (carbon footprint) is considerably higher than traditional production-based methods would suggest. Furthermore, the consumption-based inventory helps highlight the role of goods and services (and associated purchasing behaviors) more so than do production-based methods. Accordingly, a consumption-based perspective opens new opportunities for many states and their local government partners to reduce GHG emissions, such as initiatives to advance lower-carbon public sector or household consumption, that are well within their sphere of influence. State and local governments should consider conducting consumption-based GHG inventories and adopting consumption-based emission reductions targets in order to broaden the reach and effectiveness of state and local actions in reducing global GHG emissions. Consumption-based frameworks should be viewed as a complement to, but not a substitute for, production-based (in-state) GHG emissions inventories and targets.

Structural basis for selective small molecule kinase inhibition of activated c-Met.

The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix αC and the G loop to generate a viable active site. Helix αC adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

Evaluating scoring functions for docking and designing beta-secretase inhibitors.

Several simple scoring methods were examined for 2 series of beta-secretase (BACE-1) inhibitors to identify a docking/scoring protocol which could be used to design BACE-1 inhibitors in a drug discovery program. Both the PLP1 score and MMFFs interaction energy (E(inter)) performed as well or better than more computationally intensive methods for a set of substrate-based inhibitors, while the latter performed well for both sets of inhibitors.