Increasing Naloxone Co-Prescribing Among At-Risk Individuals: Evaluation of a Quality Improvement Project in a Large Health System

Background: Naloxone availability and early administration is key in preventing death following opioid overdose. The CDC advises that naloxone should be made available to all at-risk individuals. In 2017, providers at Maine Medical Center noted that only 6% of at-risk patients had naloxone prescriptions Methods: Included in this study were all patients of MaineHealth, a health system comprising 9 hospitals and 30 primary care practices, serving approximately 1.1 million patients. Between 2017 and 2020, we implemented several system-wide quality improvement interventions to increase rates of naloxone co-prescribing among at-risk individuals. Risk factors included prescribed opioids ≥50 morphine milligram equivalents, concurrent prescriptions for opioids and benzodiazepines or sedative/hypnotics, a diagnosis of substance use disorder, or a history of opioid overdose. Our interventions included (1) a standing order for naloxone in the hospital pharmacy, (2) in-person naloxone trainings for all clinical and non-clinical primary care staff, (3) online training modules, (4) guidelines on naloxone co-prescribing sent via email, and (5) automated alerts in the electronic medical record (EMR). To evaluate these interventions, the EMR for, was queried for patients with one or more risk factors for opioid overdose, and whether they had naloxone on their medication list between 2017 and 2020. Results: Over the course of the study period, overall rate of naloxone co-prescribing system-wide increased from 0.4% to 26% of patients. Automatic EMR alerts were associated with an increase of 4.5%, the largest single-quarter increase. Online education modules and guideline dissemination were associated with smaller increases of 0.9% and 3% in the two quarters following their implementation. In-person trainings and making naloxone available without a prescription were followed by Conclusions: Our most effective intervention was automatic alerts in the EMR, while e online trainings and guidelines produced modest effects. A notable increase was also seen in one hospital system whose entire leadership and staff deliberately prioritized increasing naloxone access. Even with these gains, we have not yet achieved adequate co-prescribing across our system

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field