Statewide efforts to address the opioid epidemic: Results from a national survey of single state agencies.

BACKGROUND: Single State Agencies (SSAs) are at the forefront of efforts to address the nation's opioid epidemic, responsible for allocating billions of dollars in federal, state, and local funds to ensure service quality, promote best practices, and expand access to care. Federal expenditures to SSAs have more than tripled since the early years of the epidemic, yet, it is unclear what initiatives SSAs have undertaken to address the crisis and how they are financing these efforts. METHODS: This study used data from an internet-based survey of SSAs, conducted by the University of Chicago Survey Lab from January to December 2021 (response rate of 94 %). The survey included a set of 14 items identifying statewide efforts to address the opioid epidemic and six funding sources. We calculated the percentage of SSAs that supported each statewide effort and the percentage of SSAs reporting use of each source of funding across the 14 statewide efforts. RESULTS: Treatment of opioid-related overdose figured most prominently among statewide efforts, with all SSAs providing funding for naloxone distribution and all but one SSA supporting naloxone training. Recovery support services, Project ECHO, and Hub and Spoke models were supported by the vast majority of SSAs. Statewide efforts related to expanding access to medications for opioid use disorder (MOUD) received somewhat less support, with 45 % of SSAs supporting mobile methadone/MOUD clinics/programs and 70 % supporting buprenorphine in emergency departments. A relatively low proportion of SSAs (54 %) provided support for syringe services programs. State Opioid Response (SOR) funds were the most common funding source reported by SSAs (57 % of SSAs), followed by block grant funds (19 %) and other state funding (15 %). CONCLUSION: Results highlight a range of SSA efforts to address the nation's opioid epidemic. Limited adoption of efforts to expand access to MOUD and harm reduction services may represent missed opportunities. The uncertainty over reauthorization of the SOR grant post-2025 also raises concerns over sustainability of funding for many of these statewide initiatives.

Carriers of the Complex Allele HFE c.[187C>G;340+4T>C] Have Increased Risk of Iron Overload in São Miguel Island Population (Azores, Portugal).

Iron overload is associated with acquired and genetic conditions, the most common being hereditary hemochromatosis (HH) type-I, caused by HFE mutations. Here, we conducted a hospital-based case-control study of 41 patients from the São Miguel Island (Azores, Portugal), six belonging to a family with HH type-I pseudodominant inheritance, and 35 unrelated individuals fulfilling the biochemical criteria of iron overload compatible with HH type-I. For this purpose, we analyzed the most common HFE mutations- c.845G>A [p.Cys282Tyr], c.187C>G [p.His63Asp], and c.193A>T [p.Ser65Cys]. Results revealed that the family's HH pseudodominant pattern is due to consanguineous marriage of HFE-c.845G>A carriers, and to marriage with a genetically unrelated spouse that is a -c.187G carrier. Regarding unrelated patients, six were homozygous for c.845A, and three were c.845A/c.187G compound heterozygous. We then performed sequencing of HFE exons 2, 4, 5 and their intron-flanking regions. No other mutations were observed, but we identified the -c.340+4C [IVS2+4C] splice variant in 26 (74.3%) patients. Functionally, the c.340+4C may generate alternative splicing by HFE exon 2 skipping and consequently, a protein missing the α1-domain essential for HFE/ transferrin receptor-1 interactions. Finally, we investigated HFE mutations configuration with iron overload by determining haplotypes and genotypic profiles. Results evidenced that carriers of HFE-c.187G allele also carry -c.340+4C, suggesting in-cis configuration. This data is corroborated by the association analysis where carriers of the complex allele HFE-c.[187C>G;340+4T>C] have an increased iron overload risk (RR = 2.08, 95% CI = 1.40-2.94, p<0.001). Therefore, homozygous for this complex allele are at risk of having iron overload because they will produce two altered proteins--the p.63Asp [c.187G], and the protein lacking 88 amino acids encoded by exon 2. In summary, we provide evidence that the complex allele HFE-c.[187C>G;340+4T>C] has a role, as genetic predisposition factor, on iron overload in the São Miguel population. Independent replication studies in other populations are needed to confirm this association.