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.

A Learning Assessment to Increase Diversity in Academic Health Sciences.

Importance: Strategies and innovations to advance racial and ethnic equity in recruitment, promotion, and retention at academic health science institutions are needed. Objective: This learning assessment aims to isolate evidence-based strategies to advance racial equity in the academic health sciences, which have implications for policy and institution-level interventions. Evidence Review: This learning assessment used a mixed-methods approach, including a quantitative survey, qualitative in-depth interviews, and a scoping literature review. Survey respondents were recruited from outreach lists that included researchers working with racial and ethnic minoritized populations. In-depth interviews were conducted among 60 university administrators, faculty/staff, scholars, students, and individuals affiliated with governmental, nongovernmental, and identity-based professional associations. A search of the literature in PsycINFO, MEDLINE, ERIC, Education Source, Academic Search Ultimate, and CINAHL was conducted for the scoping review. The scoping review included 366 primary articles of studies evaluating strategies to advance racial and ethnic equity at academic health science institutions. Findings: The survey yielded analyzable results from 328 individuals, including faculty, students, administrators, or staff, and individuals not currently employed at or enrolled full time at a university or college. The interviews included 60 participants with a mean (SD) age of 49.3 (16.5) years, and 39 (65%) were female. The scoping review included 366 primary research articles that met inclusion criteria for analysis. Data were analyzed individually across the survey, interviews, and scoping review, and findings were triangulated. While each of the 3 assessments yielded unique findings, 13 common themes emerged across all project components. Results revealed strategies implemented and evaluated successfully, as well as challenges and barriers to advancing equity in the academic health sciences. Conclusions and Relevance: In this study, 13 meaningful strategies emerged across the survey, in-depth interviews, and scoping review. Through triangulation of findings, recommendations of actionable steps were made.

Chronic Thromboembolic Pulmonary Hypertension.

This JAMA Insights discusses the symptoms, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension.

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.

In severe, uncontrolled asthma, tezepelumab reduced exacerbations over 1 y regardless of type 2 inflammation level.

SOURCE CITATION: Corren J, Menzies-Gow A, Chupp G, et al. Efficacy of tezepelumab in severe, uncontrolled asthma: pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med. 2023;208:13-24. 37015033.

In COPD with type 2 inflammation despite inhaled triple therapy, dupilumab safely reduced exacerbations.

SOURCE CITATION: Bhatt SP, Rabe KF, Hanania NA, et al; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023;389;205-214.37272521.

In symptomatic PAH, adding sotatercept to stable background therapy improved 6-min walk distance at 24 wk.

SOURCE CITATION: Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388:1478-1490. 36877098.

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.

Assessment of the Association of COPD and Asthma with In-Hospital Mortality in Patients with COVID-19. A Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

Together, chronic obstructive pulmonary disease (COPD) and asthma account for the most common non-infectious respiratory pathologies. Conflicting preliminary studies have shown varied effect for COPD and asthma as prognostic factors for mortality in coronavirus disease 2019 (COVID-19). The aim of this study was to explore the association of COPD and asthma with in-hospital mortality in patients with COVID-19 by systematically reviewing and synthesizing with a meta-analysis the available observational studies. MEDLINE, Scopus, and medRxiv databases were reviewed. A random-effects model meta-analysis was used, and I-square was utilized to assess for heterogeneity. In-hospital mortality was defined as the primary endpoint. Sensitivity and meta-regression analyses were performed. Thirty studies with 21,309 patients were included in this meta-analysis (1465 with COPD and 633 with asthma). Hospitalized COVID-19 patients with COPD had higher risk of death compared to those without COPD (OR: 2.29; 95% CI: 1.79-2.93; I2 59.6%). No significant difference in in-hospital mortality was seen in patients with and without asthma (OR: 0.87; 95% CI: 0.68-1.10; I2 0.0%). The likelihood of death was significantly higher in patients with COPD that were hospitalized with COVID-19 compared to patients without COPD. Further studies are needed to assess whether this association is independent or not. No significant difference was demonstrated in COVID-19-related mortality between patients with and without asthma.

Beyond corticosterone: The acute stress response increases DNA damage in house sparrows.

Although corticosterone (Cort) has been the predominant metric used to assess acute stress in birds, it does not always accurately reflect how an animal copes with a stressor. Downstream measurements may be more reliable. In the current study, we tested the hypothesis that acute increases in DNA damage could be used to assess stressor exposure. Studies have shown DNA damage increases in response to stress-related hormones in vitro; however, this has not yet been thoroughly applied in wild animals. We exposed house sparrows (Passer domesticus) to a 30- or 120-min restraint stressor and took blood samples at 0, 30, 60, and 120 min to measure Cort, DNA damage, and uric acid. Both treatments increased DNA damage and Cort, and decreased uric acid. It thus appears that DNA damage can reflect acute stressor exposure. To improve the usability of DNA damage as a metric for stress, we also tested the impacts of sample storage on DNA damage. Leaving red blood cells on ice for up to 24 hr, only slightly influenced DNA damage. Freezing blood samples for 1-4 weeks substantially increased DNA damage. These findings emphasize the importance of reducing variation between samples by assaying them together whenever possible. Overall, these results indicate that assessing DNA damage is a valid method of assessing acute stressor exposure that is suitable for both laboratory- and field-based studies; however, additional research is needed on the molecular dynamics of nucleated red blood cells, including whether and how their DNA is repaired.

Recovery from repeated stressors: Physiology and behavior are affected on different timescales in house sparrows.

For decades, researchers across disciplines have been captivated by classifying, diagnosing, and avoiding the consequences of chronic stress. Despite the vast body of literature this has generated, we still lack the ability to predict which individuals or populations may be susceptible to stress-related pathologies. One critical unanswered question is whether the impacts of repeated stressors are reversible, or if instead they permanently alter an individual. In this study, we exposed house sparrows (Passer domesticus) to 6 days of random, repeated stressors, permitted them 0, 1, 3, or 6 days to recover, and then assessed changes in their body mass, hypothalamic-pituitaryadrenal (HPA) axis (baseline, stress-induced corticosterone, negative feedback strength), immune function, uric acid concentrations, DNA damage levels, and perch hopping activity. Body mass did not vary between groups after recovery. We found that the HPA axis and perch hopping were not significantly impacted by the 6 days of stressors, but that uric acid and DNA damage increased. Short recovery periods tended to negatively affect the HPA axis and reduced uric acid levels, but these were reversed with longer recovery periods. Following the recovery periods, the birds experienced an additional 6 days of random stressors and their responses were assessed again. All recovery times reduced perch hopping and immune function, but paradoxically, DNA damage was highest in the birds that had the longest amount of time to recover. These results show that recovery time affects responses to subsequent chronic stress in complex ways, and highlight the importance of multimodal, interdisciplinary approaches to studying stress physiology.

Atrial fibrillation inducibility during cavo-tricuspid isthmus dependent atrial flutter ablation for the prediction of clinical atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and cavo-tricuspid isthmus (CTI) dependent atrial flutter (AFL) are two separate entities that coexist in a significant percentage of patients. METHODS: We sought to investigate whether AF inducibility during CTI AFL ablation predicted the occurrence of AF at follow up after AFL ablation. Univariate and multivariate analyses were performed. RESULTS: A total of 154 patients (male: 72%, age: 61±13) with AFL and without history of AF were included. All patients underwent successful CTI dependent AFL ablation demonstrated by bidirectional block. During ablation, AF was seen or induced in 28 (18%) patients. After a mean follow up of 34±24months a total of 50 patients (32%) were noted with clinically manifest AF. From the patients who had inducible AF during AFL ablation, 50% developed post-procedural AF. From those in whom AF could not be induced, only 29% were documented with AF after ablation. Univariate and multivariate analyses revealed that only age and AF inducibility during AFL ablation were predictors of AF. Univariate analysis (age p=0.038 and inducible AF p=0.032 with odds ratio of 1.030 [95% CI (1.002-1.059)] and 2.500 [95% CI (1.084-5.765)], respectively) and multivariate analyses (age p=0.011 and inducible AF p=0.016 with adjusted odds ratio of 1.043 [95% CI (1.010-1.077)] and 3.293 [95% CI (1.250-8.676)], respectively). CONCLUSION: AF inducibility in patients undergoing CTI AFL without history of AF is a strong predictor of AF occurrence in the future. Appropriate cardiology follow-up must be encouraged in this high-risk population as stroke prevention strategies can be appropriately introduced in a timely matter especially in patients with elevated CHA2DS2-VASc scores (≥2).

Thermochemical ablation in an ex-vivo porcine liver model using acetic acid and sodium hydroxide: proof of concept.

PURPOSE: To establish proof of concept in tissue, using the exothermic neutralization reaction of acetic acid and sodium hydroxide in ex vivo porcine liver and to conduct an initial probe into the relationships of volume and concentration of reagents to temperatures and the areas affected. MATERIALS AND METHODS: A total of 0.5 mL or 2 mL of either 5 mole/L or 10 mole/L acid and base solutions was injected simultaneously into the periphery of ex vivo porcine liver using a prototype injection device. Tissue temperature was recorded at the injection site for 5 minutes using a type T thermocouple temperature probe inserted parallel to and near the tip of the injection device. The injections were repeated for infrared thermography, and ablated tissues were sectioned quickly and imaged. A gross photograph was captured in each case to provide correlation. RESULTS: Maximum temperatures (17°C baseline) ranged from 42.1° ± α3.34°C to 61.7° ± α10°C (P<.05) when injecting 0.5 mL of 5 mole/L reactants and 2 mL of 10 mole/L reactants, respectively. The maximum temperature measured by infrared imaging ranged from 31°-47°C. Using an infrared viewing scale from 19°-40°C, the cross-sectional area of tissue heating above baseline measured from 1.07 cm(2)± 0.45 to 4.95 cm(2)± 0.28 (P <05). CONCLUSIONS: The reaction of acetic acid and sodium hydroxide releases significant heat energy at the site of injection, and histologic changes are consistent with coagulation necrosis. Increased reagent concentration and volume were associated with larger temperature changes and larger areas of hyperthermia at gross pathology and infrared imaging.