Implementation and Uptake of the Massachusetts Drug Supply Data Stream: A Statewide Public Health-Public Safety Partnership Drug Checking Program.

CONTEXT: The illicit drug supply is rapidly evolving. Equally important to gathering drug supply data for monitoring is timely sharing of information with people who use drugs, the providers who care for them, law enforcement partners, and public health stakeholders so that efforts to avoid harmful substances, take preventive actions, and better target interventions can occur. PROGRAM: The Massachusetts Drug Supply Data Stream (MADDS) is the country's first statewide community drug checking program. Founded on public health-public safety partnerships, MADDS collects remnant drug packaging and paraphernalia with residue from people who use drugs and noncriminal samples from partnering police departments. MADDS tests samples using simultaneous immunoassay fentanyl test strips, Fourier-transform infrared spectrometry (FTIR), and off-site laboratory testing by gas chromatography-mass spectrometry (GC/MS). Results are accessible to community programs and municipalities, while trend analyses inform public health for cross-site alerts and informational bulletins. IMPLEMENTATION: MADDS was launched statewide in 2020 and rapidly expanded to a multisite program. Program staff approached communities and met with municipal police and community partners to secure written agreements to host drug checking. Community partners designed sample collection consistent with their pandemic era workflows. Consultations with stakeholders gathered feedback on design and deliverables. EVALUATION: The program tests sample donations on-site from community agencies and police departments, incorporates review by a medical toxicologist for health and safety concerns, crafts stakeholder-specific communications, and disseminates English, Spanish, and Portuguese language materials. For 2020, a total of 427 samples were tested, of which 47.1% were positive for fentanyl. By early 2021, MADDS detected shifts in cocaine purity, alerted communities of a new toxic fentanyl analogue and a synthetic cannabinoid contaminant, and confirmed the increase of xylazine (a veterinary sedative) in Massachusetts. DISCUSSION: Community drug checking programs can be collaboratively designed with public health and public safety to generate critical health and safety information for people who use drugs and the communities where they live.

The key role of the latent N-H group in Milstein's catalyst for ester hydrogenation.

We previously demonstrated that Milstein's seminal diethylamino-substituted PNN-pincer-ruthenium catalyst for ester hydrogenation is activated by dehydroalkylation of the pincer ligand, releasing ethane and eventually forming an NHEt-substituted derivative that we proposed is the active catalyst. In this paper, we present a computational and experimental mechanistic study supporting this hypothesis. Our DFT analysis shows that the minimum-energy pathways for hydrogen activation, ester hydrogenolysis, and aldehyde hydrogenation rely on the key involvement of the nascent N-H group. We have isolated and crystallographically characterized two catalytic intermediates, a ruthenium dihydride and a ruthenium hydridoalkoxide, the latter of which is the catalyst resting state. A detailed kinetic study shows that catalytic ester hydrogenation is first-order in ruthenium and hydrogen, shows saturation behavior in ester, and is inhibited by the product alcohol. A global fit of the kinetic data to a simplified model incorporating the hydridoalkoxide and dihydride intermediates and three kinetically relevant transition states showed excellent agreement with the results from DFT.