Trends in concomitant and single opioid and benzodiazepine exposures reported to the California Poison Control System following the Centers for Disease Control and Prevention release of opioid guidelines in 2016.

INTRODUCTION: In March 2016, the Centers for Disease Control and Prevention released the Guideline for Prescribing Opioids for Chronic Pain, intended for primary care clinicians. One recommendation advised against concurrent prescription of opioids and benzodiazepines. Although existing research suggests a reduction in co-prescribing of these drug classes by clinicians after guideline release, there are limited data assessing its possible effect on patient medical outcomes, such as overdoses. METHODS: This retrospective observational study analyzed opioid and benzodiazepine exposures, alone or in combination, reported to the California Poison Control System from January 2012 to June 2021. Interrupted time series analyses identified the difference in monthly call volume between pre- and post-guideline release. For exposures resulting in serious medical outcomes, additional analyses assessed trends and identified associated variables. RESULTS: There was no significant change in concomitant opioid and benzodiazepine exposures reported to California Poison Control System between pre- and post-guideline release. Compared to pre-guideline release, exposures to a single opioid or to a single benzodiazepine significantly decreased by 1.07 (95% CI: -1.62, -0.51) and 1.82 (95% CI: -2.33, -1.31) calls per month, respectively, after the guideline release. For exposure calls associated with serious medical outcomes, there was a significant increase of 0.11 (95% CI: 0.04, 0.18) and 0.2 (95% CI: 0.05, 0.34) calls per month for concomitant opioid and benzodiazepine and single opioid exposures, respectively, following guideline release. DISCUSSION: The guideline release appeared to have a variable association with exposures to single opioid, single benzodiazepines, and concomitant opioid and benzodiazepine cases reported to California Poison Control System. Although exposures to opioids or benzodiazepines alone significantly decreased after guideline release, there was no significant change in concomitant exposures. Additionally, for exposures associated with serious medical outcomes, concomitant exposures, and single opioid exposures significantly increased following guideline release. CONCLUSION: Our results suggest that the guideline was not associated with a corresponding decrease in the number of concomitant poisoning exposures reported to California Poison Control System. Additional interventions may be needed to reduce concomitant exposures to opioids and benzodiazepines.

Chromatin imaging and new technologies for imaging the nucleome.

Synergistic developments in advanced fluorescent imaging and labeling techniques enable direct visualization of the chromatin structure and dynamics at the nanoscale level and in live cells. Super-resolution imaging encompasses a class of constantly evolving techniques that break the diffraction limit of fluorescence microscopy. Structured illumination microscopy provides a twofold resolution improvement and can readily achieve live multicolor imaging using conventional fluorophores. Single-molecule localization microscopy increases the spatial resolution by approximately 10-fold at the expense of slower acquisition speed. Stimulated emission-depletion microscopy generates a roughly fivefold resolution improvement with an imaging speed proportional to the scanning area. In parallel, advanced labeling strategies have been developed to "light up" global and sequence-specific DNA regions. DNA binding dyes have been exploited to achieve high labeling densities in single-molecule localization microscopy and enhance contrast in correlated light and electron microscopy. New-generation Oligopaint utilizes bioinformatics analyses to optimize the design of fluorescence in situ hybridization probes. Through sequential and combinatorial labeling, direct characterization of the DNA domain volume and length as well as the spatial organization of distinct topologically associated domains has been reported. In live cells, locus-specific labeling has been achieved by either inserting artificial loci next to the gene of interest, such as the repressor-operator array systems, or utilizing genome editing tools, including zinc finer proteins, transcription activator-like effectors, and the clustered regularly interspaced short palindromic repeats systems. Combined with single-molecule tracking, these labeling techniques enable direct visualization of intra- and inter-chromatin interactions. This article is categorized under: Laboratory Methods and Technologies > Imaging.