Harm Reduction Approach to Increasing Self-reported Safe Medication Storage Among Pregnant and Parenting People Receiving Opioid Use Disorder Treatment.

OBJECTIVES: The expansion of access to buprenorphine-naloxone (BUP-NAL) for the treatment of opioid use disorder (OUD) is critical to combat the overdose crisis. Evidence is lacking to guide providers on how to best promote BUP-NAL medication safety for their patients. This study assessed (1) the current medication storage practices among a sample of pregnant and parenting people receiving BUP-NAL for OUD; (2) the feasibility and acceptability of providing a lockbox for safe medication storage. METHODS: Pregnant and/or parenting patients receiving sublingual BUP-NAL in an outpatient OUD clinic were recruited between June and November 2021. Participants completed a baseline survey, received a lockbox, and a follow-up survey 3 to 8 weeks later. The primary outcome of current self-reported safe medication storage practice was defined by storing BUP-NAL in a locked/latched place "almost always" or "always" on the baseline survey. Outcomes were analyzed using simple proportions. RESULTS: Sixty-three participants completed the baseline survey, and 50 completed the follow-up survey. Baseline survey results indicated that only a quarter of patients (26.6%) were practicing safe BUP-NAL medication storage practices. At follow up, 93.6% of patients were using the lockbox provided by the study, 93.4% reported being satisfied with the lockbox, and most participants (89.3%) reported safe BUP-NAL medication storage practices. CONCLUSIONS: Many pregnant and parenting patients with OUD receiving BUP-NAL do not store their medications safely. The provision of a lockbox as part of OUD treatment is a feasible, acceptable, and potentially effective harm reduction intervention.

Proteases Activate Pregnancy Neutrophils by a Protease-Activated Receptor 1 Pathway: Epigenetic Implications for Preeclampsia.

We tested a novel hypothesis that elevated levels of proteases in the maternal circulation of preeclamptic women activate neutrophils due to their pregnancy-specific expression of protease-activated receptor 1 (PAR-1). Plasma was collected longitudinally from normal pregnant and preeclamptic women and analyzed for MMP-1 and neutrophil elastase. Neutrophils were isolated for culture and confocal microscopy. Omental fat was collected for immunohistochemistry. Circulating proteases were significantly elevated in preeclampsia. Confocal microscopy revealed that tet methylcytosine dioxygenase 2 (TET2), a DNA de-methylase, and p65 subunit of NF-κB were strongly localized to the nucleus of untreated neutrophils of preeclamptic women, but in untreated neutrophils of normal pregnant women they were restricted to the cytosol. Treatment of normal pregnancy neutrophils with proteases activated PAR-1, leading to activation of RhoA kinase (ROCK), which triggered translocation of TET2 and p65 from the cytosol into the nucleus, mimicking the nuclear localization in neutrophils of preeclamptic women. IL-8, an NF-κB-regulated gene, increased in association with TET2 and p65 nuclear localization. Co-treatment with inhibitors of PAR-1 or ROCK prevented nuclear translocation and IL-8 did not increase. Treatment of preeclamptic pregnancy neutrophils with inhibitors emptied the nucleus of TET2 and p65, mimicking the cytosolic localization of normal pregnancy neutrophils. Expression of PAR-1 and TET2 were markedly increased in omental fat vessels and neutrophils of preeclamptic women. We conclude that elevated levels of circulating proteases in preeclamptic women activate neutrophils due to their pregnancy-specific expression of PAR-1 and speculate that TET2 DNA de-methylation plays a role in the inflammatory response.