Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

A Retrospective Review: Our Experience With an Adhesive-Based Pigmented Lesion Assay Used to Evaluate Cutaneous Lesions Suspicious for Melanoma.

BACKGROUND: Being one of the largest dermatology groups in the country with an in-house pathology laboratory, we have seen a significant increase in the number of adhesive-based pigmented lesion assays (ABPLAs) in addition to biopsies and excisions following a moderate-risk or high-risk result with this test. OBJECTIVE: To report our clinical experience and independently confirm that our results with this ABPLA (Pigmented lesion assay, DermTech. San Diego, CA) are consistent with the results of the validation studies completed by the test manufacturer. METHODS: A retrospective review of our electronic medical records for results of ABPLAs, corresponding histopathologic results and available clinical follow-up, along with their statistical analysis was completed. RESULTS: After reviewing our electronic medical records, we found that 893 ABPLAs for pigmented lesions concerning for melanoma were obtained in a period of 14 months. Of the 893 ABPLAs completed, 161 biopsies and excisions were performed after the initial results of these assays. Additional clinical follow-up data were recorded and used for the statistical analysis of the performance and accuracy of this test. LIMITATIONS: The small number of lesions reported as low risk for melanoma with corresponding histopathologic results limits our evaluation of the performance of this test. In addition, there may have been some melanomas that were not identified because the duration of the clinical follow-up was insufficient or because some patients were lost to follow-up. CONCLUSION: In our experience this ABPLA has a sensitivity of 92.0%, a specificity of 79.5%, a positive predictive value of 16.9%, and a negative predictive value of 99.5% for the detection of melanoma.

Corals sustain growth but not skeletal density across the Florida Keys Reef Tract despite ongoing warming.

Through the continuous growth of their carbonate skeletons, corals record information about past environmental conditions and their effect on colony fitness. Here, we characterize century-scale growth records of inner and outer reef corals across ~200 km of the Florida Keys Reef Tract (FKRT) using skeletal cores extracted from two ubiquitous reef-building species, Siderastrea siderea and Pseudodiploria strigosa. We find that corals across the FKRT have sustained extension and calcification rates over the past century but have experienced a long-term reduction in skeletal density, regardless of reef zone. Notably, P. strigosa colonies exhibit temporary reef zone-dependent reductions in extension rate corresponding to two known extreme temperature events in 1969-1970 and 1997-1998. We propose that the subtropical climate of the FKRT may buffer corals from chronic growth declines associated with climate warming, though the significant reduction in skeletal density may indicate underlying vulnerability to present and future trends in ocean acidification.

A numerical framework for genetic hitchhiking in populations of variable size.

Natural selection on beneficial or deleterious alleles results in an increase or decrease, respectively, of their frequency within the population. Due to chromosomal linkage, the dynamics of the selected site affect the genetic variation at nearby neutral loci in a process commonly referred to as genetic hitchhiking. Changes in population size, however, can yield patterns in genomic data that mimic the effects of selection. Accurately modeling these dynamics is thus crucial to understanding how selection and past population size changes impact observed patterns of genetic variation. Here, we model the evolution of haplotype frequencies with the Wright-Fisher diffusion to study the impact of selection on linked neutral variation. Explicit solutions are not known for the dynamics of this diffusion when selection and recombination act simultaneously. Thus, we present a method for numerically evaluating the Wright-Fisher diffusion dynamics of 2 linked loci separated by a certain recombination distance when selection is acting. We can account for arbitrary population size histories explicitly using this approach. A key step in the method is to express the moments of the associated transition density, or sampling probabilities, as solutions to ordinary differential equations. Numerically solving these differential equations relies on a novel accurate and numerically efficient technique to estimate higher order moments from lower order moments. We demonstrate how this numerical framework can be used to quantify the reduction and recovery of genetic diversity around a selected locus over time and elucidate distortions in the site-frequency-spectra of neutral variation linked to loci under selection in various demographic settings. The method can be readily extended to more general modes of selection and applied in likelihood frameworks to detect loci under selection and infer the strength of the selective pressure.