The impact of the abuse-deterrent reformulation of extended-release T OxyContin on prescription pain reliever misuse and heroin initiation

The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to the reformulation were considered the exposed group and those who misused other prescription pain relievers prior to the reformulation were considered the unexposed group. We employed multivariate logistic regression under a difference-in-differences framework to examine the effect of the re- formulation on five dichotomous outcomes: prescription pain reliever misuse; prescription pain reliever use disorder; heroin use; heroin use disorder; and heroin initiation. We found a net reduction in the odds of pre- scription pain reliever misuse (OR:0.791, p \u3c 0.001) and heroin initiation (OR:0.422, p = 0.011) after the reformulation for the exposed group relative to the unexposed group. We found no statistically significant effects of the reformulation on prescription pain reliever use disorder (OR: 0.934, p = 0.524), heroin use (OR: 1.014p = 0.941), and heroin use disorder (OR: 1.063, p = 0.804). Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation

AgMIP Training in Multiple Crop Models and Tools

The Agricultural Model Intercomparison and Improvement Project (AgMIP) has the goal of using multiple crop models to evaluate climate impacts on agricultural production and food security in developed and developing countries. There are several major limitations that must be overcome to achieve this goal, including the need to train AgMIP regional research team (RRT) crop modelers to use models other than the ones they are currently familiar with, plus the need to harmonize and interconvert the disparate input file formats used for the various models. Two activities were followed to address these shortcomings among AgMIP RRTs to enable them to use multiple models to evaluate climate impacts on crop production and food security. We designed and conducted courses in which participants trained on two different sets of crop models, with emphasis on the model of least experience. In a second activity, the AgMIP IT group created templates for inputting data on soils, management, weather, and crops into AgMIP harmonized databases, and developed translation tools for converting the harmonized data into files that are ready for multiple crop model simulations. The strategies for creating and conducting the multi-model course and developing entry and translation tools are reviewed in this chapter

Guide for Regional Integrated Assessments: Handbook of Methods and Procedures, Version 5.1

The purpose of this handbook is to describe recommended methods for a trans-disciplinary, systems-based approach for regional-scale (local to national scale) integrated assessment of agricultural systems under future climate, bio-physical and socio-economic conditions. An earlier version of this Handbook was developed and used by several AgMIP Regional Research Teams (RRTs) in Sub-Saharan Africa (SSA) and South Asia (SA)(AgMIP handbook version 4.2, www.agmip.org/regional-integrated-assessments-handbook/). In contrast to the earlier version, which was written specifically to guide a consistent set of integrated assessments across SSA and SA, this version is intended to be more generic such that the methods can be applied to any region globally. These assessments are the regional manifestation of research activities described by AgMIP in its online protocols document (available at www.agmip.org). AgMIP Protocols were created to guide climate, crop modeling, economics, and information technology components of its projects

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The impact of the abuse-deterrent reformulation of extended-release T OxyContin on prescription pain reliever misuse and heroin initiation

The introduction of abuse-deterrent OxyContin in 2010 was intended to reduce its misuse by making it more tamper resistant. However, some studies have suggested that this reformulation might have had unintended consequences, such as increases in heroin-related deaths. We used the 2005–2014 cross-sectional U.S. National Survey on Drug Use and Health to explore the impact of this reformulation on intermediate outcomes that precede heroin-related deaths for individuals with a history of OxyContin misuse. Our study sample consisted of adults who misused any prescription pain reliever prior to the reformulation of OxyContin (n = 81,400). Those who misused OxyContin prior to the reformulation were considered the exposed group and those who misused other prescription pain relievers prior to the reformulation were considered the unexposed group. We employed multivariate logistic regression under a difference-in-differences framework to examine the effect of the re- formulation on five dichotomous outcomes: prescription pain reliever misuse; prescription pain reliever use disorder; heroin use; heroin use disorder; and heroin initiation. We found a net reduction in the odds of pre- scription pain reliever misuse (OR:0.791, p \u3c 0.001) and heroin initiation (OR:0.422, p = 0.011) after the reformulation for the exposed group relative to the unexposed group. We found no statistically significant effects of the reformulation on prescription pain reliever use disorder (OR: 0.934, p = 0.524), heroin use (OR: 1.014p = 0.941), and heroin use disorder (OR: 1.063, p = 0.804). Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation

Inhibition of Survivin and Aurora B Kinase Sensitizes Mesothelioma Cells by Enhancing Mitotic Arrests

Purpose: Survivin, a member of the inhibitor of apoptosis gene family, has also been shown to regulate mitosis. It binds Aurora B kinase and the inner centromere protein to form the chromosome passenger complex. Both Aurora B and survivin are overexpressed in many tumors. In this study, we examined whether irradiation affected survivin and Aurora B expression in mesothelioma cells, and how inhibition of these molecules affected radiosensitivity. Methods and Materials: ZM447439 and survivin antisense oligonucleotides were used to inhibit survivin and Aurora B kinase respectively. Western blot was performed to determine the expression of survivin, Aurora B, phosphorylated-histone H3 (Ser 10), and caspase cleavage. Multinucleated cells were counted using flow cytometry, and cell survival after treatment was determined using clonogenic assay. Results: At 3-Gy irradiation an increase was observed in levels of survivin and Aurora B as well as the kinase activity of Aurora B, with an increase in G2/M phase. The radiation-induced upregulation of these molecules was effectively attenuated by antisense oligonucleotides against survivin and a small-molecule inhibitor of Aurora B, ZM447439. Dual inhibition of survivin and Aurora B synergistically radiosensitized mesothelioma cells with a dose enhancement ratio of 2.55. This treatment resulted in increased formation of multinucleated cells after irradiation but did not increase levels of cleaved caspase 3. Conclusion: Inhibition of survivin and Aurora B induces mitotic cell arrest in mesothelioma cells after irradiation. These two proteins may be potential therapeutic targets for the enhancement of radiotherapy in malignant pleural mesothelioma

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally