The Emergency Department Longitudinal Integrated Care (ED-LINC) intervention targeting opioid use disorder: A pilot randomized clinical trial.

INTRODUCTION: Opioid use disorder (OUD) and related comorbid conditions are highly prevalent among patients presenting to emergency department (ED) settings. Research has developed few comprehensive disease management strategies for at-risk patients presenting to the ED that both decrease illicit opioid use and improve initiation and retention in medication treatment for OUD (MOUD). METHODS: The research team conducted a pilot pragmatic clinical trial that randomized 40 patients presenting to a single ED to a collaborative care intervention (n = 20) versus usual care control (n = 20) conditions. Interviewers blinded to patient intervention and control group status followed-up with participants at 1, 3, and 6 months after presentation to the ED. The 3-month Emergency Department Longitudinal Integrated Care (ED-LINC) collaborative care intervention for patients at risk for OUD included: 1) a Brief Negotiated Interview at bedside, 2) overdose education and facilitation of MOUD, 3) longitudinal proactive care management, 4) utilization of the statewide health information exchange platform for 24/7 tracking of recurrent ED utilization, and 5) weekly caseload supervision that incorporated measurement-based care treatment assessment with stepped-up care for patients with recalcitrant symptoms. RESULTS: Overall, the ED-LINC intervention was feasibly delivered and acceptable to patients. The pilot study achieved >80% follow-up rates at 1, 3, and 6 months. In adjusted longitudinal mixed model regression analyses, no statistically significant differences existed in days of opioid use over the past 30 days for ED-LINC intervention patients when compared to patients receiving usual care (incidence-rate ratio (IRR) 1.50, 95% CI 0.54-4.16). The unadjusted mean number of days of illicit opioid use decreased at the 1-month and 3-month follow-up time points for both groups. ED-LINC intervention patients had increased rates of MOUD initiation compared to control patients (50% versus 30%); intervention versus control comparisons did not achieve statistical significance, although power to detect significant differences in the pilot was limited. CONCLUSIONS: The ED-LINC intervention for patients with OUD can be feasibly implemented and warrants testing in larger scale, adequately powered randomized pragmatic clinical trial investigations. CLINICALTRIALS: gov NCT03699085.

Delayed neurologic and behavioral effects of subtoxic doses of cholinesterase inhibitors.

We tested the hypothesis that pyridostigmine bromide (PB) intake and/or low-level sarin exposure, suggested by some as causes of the symptoms experienced by Persian Gulf War veterans, induce neurobehavioral dysfunction that outlasts their effects on cholinesterase. Adult male Sprague-Dawley rats were treated during 3 weeks with s.c. saline, PB in drinking water (80 mg/l), sarin (62.5 microg/kg; 0.5x LD(50), three times/week s.c.), or PB in drinking water + sarin. Animals were tested for passive avoidance, nociceptive threshold, acoustic startle, and open field activity 2, 4, or 16 weeks after treatment. Two weeks after sarin, acoustic startle was enhanced, whereas distance explored in the open field decreased. These effects were absent with PB + sarin or PB by itself. No effect on any variable was found at 4 weeks, whereas at 16 weeks sarin induced a decrease and PB + sarin induced an increase in habituation in the open field test. Nociceptive threshold was elevated in the PB + sarin group at 16 weeks. No effect of treatment on passive avoidance was noted in any group. Brain regional acetylcholinesterase and cholineacetyltransferase activities were not affected at any time after treatment, but muscarinic receptors were down-regulated in hippocampus, caudate putamen, and mesencephalon in the sarin group at 2 weeks. In conclusion, this study gives further support to the use of PB against nerve agent poisoning and does not support the hypothesis that delayed symptoms experienced by Persian Gulf War veterans could be due to PB, alone or in association with low-level sarin exposure.