Predictive Models to Assess Risk of Persistent Opioid Use, Opioid Use Disorder, and Overdose.

BACKGROUND: This systematic review summarizes the development, accuracy, quality, and clinical utility of predictive models to assess the risk of opioid use disorder (OUD), persistent opioid use, and opioid overdose. METHODS: In accordance with Preferred Reporting Items for a Systematic Review and Meta-analysis guidelines, 8 electronic databases were searched for studies on predictive models and OUD, overdose, or persistent use in adults until June 25, 2023. Study selection and data extraction were completed independently by 2 reviewers. Risk of bias of included studies was assessed independently by 2 reviewers using the Prediction model Risk of Bias ASsessment Tool (PROBAST). RESULTS: The literature search yielded 3130 reports; after removing 199 duplicates, excluding 2685 studies after abstract review, and excluding 204 studies after full-text review, the final sample consisted of 41 studies that developed more than 160 predictive models. Primary outcomes included opioid overdose (31.6% of studies), OUD (41.4%), and persistent opioid use (17%). The most common modeling approach was regression modeling, and the most common predictors included age, sex, mental health diagnosis history, and substance use disorder history. Most studies reported model performance via the c statistic, ranging from 0.507 to 0.959; gradient boosting tree models and neural network models performed well in the context of their own study. One study deployed a model in real time. Risk of bias was predominantly high; concerns regarding applicability were predominantly low. CONCLUSIONS: Models to predict opioid-related risks are developed using diverse data sources and predictors, with a wide and heterogenous range of accuracy metrics. There is a need for further research to improve their accuracy and implementation.

Investigating the effects of acute and chronic stress on DNA damage.

A hallmark of the vertebrate stress response is a rapid increase in glucocorticoids and catecholamines; however, this does not mean that these mediators are the best, or should be the only, metric measured when studying stress. Instead, it is becoming increasingly clear that assaying a suite of downstream metrics is necessary in stress physiology. One component of this suite could be assessing double-stranded DNA damage (dsDNA damage), which has recently been shown to increase in blood with both acute and chronic stress in house sparrows (Passer domesticus). To further understand the relationship between stress and dsDNA damage, we designed two experiments to address the following questions: (1) how does dsDNA damage with chronic stress vary across tissues? (2) does the increase in dsDNA damage during acute stress come from one arm of the stress response or both? We found that (1) dsDNA damage affects tissues differently during chronic stress and (2) the hypothalamic-pituitary-adrenal axis influences dsDNA damage with acute stress, but the sympathetic-adreno-medullary system does not. Surprisingly, our data are not explained by studies on changes in hormone receptor levels with chronic stress, so the underlying mechanism remains unclear.

Background DNA damage is higher in summer than winter in both free-living and captive birds.

Although stress can cause overall damage to the genome, it is currently unknown whether normal background damage to DNA varies throughout the annual cycle. If DNA damage did vary seasonally, it would have major implications on environmental-genomic interactions. We measured background DNA double-stranded breaks using the neutral comet assay in five tissues (nucleated red blood cells, abdominal fat, hippocampus, hypothalamus, and liver) in four cohorts of house sparrows (Passer domesticus): free-living summer, captives on a summer light cycle, free-living winter, and captives on a winter light cycle. The experiment was designed to answer three questions: (1) Is red blood cell DNA damage representative of other tissues? (2) Is DNA damage in captive birds representative of DNA damage in free-living birds? (3) Does DNA damage show seasonality? We found that (1) blood is a representative tissue, (2) captive animals are representative of free-living animals, and (3) DNA damage is higher in the summer than in the winter. These data indicate that red blood cells can be an index of DNA damage throughout the body and that background levels of DNA damage show substantial seasonal variation. The latter result suggests the possibility that underlying molecular mechanisms of DNA damage and/or repair also change seasonally.