计量经济分析 = Econometric analysis

Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.

Oxidative stress and diabetic complications

Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031914-122957

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

Risk environments and drug harms: a social science for harm reduction approach.

Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases

Opioid-overdose laws association with opioid use and overdose mortality.

Medical cannabis has been touted as a solution to the US opioid overdose crisis since Bachhuber et al. [M. A. Bachhuber, B. Saloner, C. O. Cunningham, C. L. Barry, JAMA Intern. Med. 174, 1668–1673] found that from 1999 to 2010 states with medical cannabis laws experienced slower increases in opioid analgesic overdose mortality. That research received substantial attention in the scientific literature and popular press and served as a talking point for the cannabis industry and its advocates, despite caveats from the authors and others to exercise caution when using ecological correlations to draw causal, individual-level conclusions. In this study, we used the same methods to extend Bachhuber et al.’s analysis through 2017. Not only did findings from the original analysis not hold over the longer period, but the association between state medical cannabis laws and opioid overdose mortality reversed direction from −21% to +23% and remained positive after accounting for recreational cannabis laws. We also uncovered no evidence that either broader (recreational) or more restrictive (low-tetrahydrocannabinol) cannabis laws were associated with changes in opioid overdose mortality. We find it unlikely that medical cannabis—used by about 2.5% of the US population—has exerted large conflicting effects on opioid overdose mortality. A more plausible interpretation is that this association is spurious. Moreover, if such relationships do exist, they cannot be rigorously discerned with aggregate data. Research into therapeutic potential of cannabis should continue, but the claim that enacting medical cannabis laws will reduce opioid overdose death should be met with skepticism.

https://www.pnas.org/content/pnas/116/26/12624.full.pdf

Association between medical cannabis laws and opioid overdose mortality has reversed over time

Legal changes to increase access to naloxone for opioid overdose reversal in the United States.

Today's fentanyl crisis: Prohibition's Iron Law, revisited.

Law enforcement activity has been found to influence health risk behavior of injection drug users. Repeated measurements and mixed effects models were used to analyze the effects of an intensive long-term street-level police action to reduce open drug sales on syringe exchange program use. Utilization data for 9 months before and after the beginning of the intervention were analyzed. Use fell across all categories and time periods studied, with significant declines in use among total participants, male participants, and Black participants. Declines in use among Black and male participants were much more pronounced than decreases among White and female participants.

Corey S. Davis

Papers

Opioid-overdose laws association with opioid use and overdose mortality.

Association between medical cannabis laws and opioid overdose mortality has reversed over time

Legal changes to increase access to naloxone for opioid overdose reversal in the United States.

Today's fentanyl crisis: Prohibition's Iron Law, revisited.

Effects of an Intensive Street-Level Police Intervention on Syringe Exchange Program Use in Philadelphia, Pa