Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record

To gain a better understanding of the mechanisms by which cortisol suppresses growth during chronic stress in fish, we characterized the effects of chronic cortisol on food intake, mass gain, the expression of appetite-regulating factors, and the activity of the GH/IGF axis. Fish given osmotic pumps that maintained plasma cortisol levels at w70 or 116 ng/ml for 34 days were sampled 14, 28 and 42 days post-implantation. Relative to shams, the cortisol treatments reduced food intake by 40-60% and elicited marked increases in liver leptin (lep-a1) and brain preoptic area (POA) corticotropin-releasing factor (crf) mRNA levels. The cortisol treatments also elicited 40-80% reductions in mass gain associated with increases in pituitary gh, liver gh receptor (ghr), liver igfI and igf binding protein (igfbp)-1 and -2 mRNA levels, reduced plasma GH and no change in plasma IGF1. During recovery, while plasma GH and pituitary gh, liver ghr and igfI gene expression did not differ between treatments, the high cortisol-treated fish had lower plasma IGF1 and elevated liver igfbp1 mRNA levels. Finally, the cortisol-treated fish had higher plasma glucose levels, reduced liver glycogen and lipid reserves, and muscle lipid content. Thus, our findings suggest that the growth-suppressing effects of chronic cortisol in rainbow trout result from reduced food intake mediated at least in part by increases in liver lep-a1 and POA crf mRNA, from sustained increases in hepatic igfbp1 expression that reduce the growth-promoting actions of the GH/IGF axis, and from a mobilization of energy reserves.

The results identified critical gaps in the provision of SC treatment in VHA SRTPs. These findings suggest actionable opportunities to improve SC treatment in SRTPs, including providing training opportunities, developing or enforcing policies that support SC, implementing systems to track and report tobacco-related diagnoses and treatment, and obtaining leadership support for building a culture that encourages SC.

Osteoporosis or osteopenia are common clinical manifestations of sickle cell disease (SCD) with unclear mechanisms. Since senescence of circulating neutrophil can be modulated by signals derived from intestinal microbiome and neutrophils are abundant in bone marrow and can regulate osteoblasts and osteoclasts, we examined whether gut microbiome contributes to bone loss in SCD mice. SCD and their littermates control mice were treated with antibiotics to deplete gut microbiome. At the end of 7 weeks treatment, serum was collected for biochemistry marker measurements. Bone mass and remodeling were evaluated by dual beam X-ray absorptiometry, micro-computed tomography, and histomorphometry. Bone-related genes in tibia and barrier marker genes in the small intestine were analyzed by quantitative PCR. Antibiotic treatment rescued increased intestinal inflammatory cytokine marker genes ( Tnfα , IL17 , Ifnγ ) expression, rescued decreased intestinal barrier marker genes ( claudin 3 and claudin 15 ) expression, and rescued increased serum cytokines (IFNγ, IL27, IL10) in SCD mice. Antibiotic significantly improved decreased bone mass in SCD mice mainly through enhanced osteoblast function and increased osteoblast-related genes ( Runx2 and Igf1 ) expression in SCD mice. Our findings support that increased bacteria load augments antigenic load traversing the impaired intestinal barrier through inflammation, leading to increased inflammatory cytokines, impaired osteoblast function, and bone loss in SCD mice.

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