Communities That HEAL Intervention and Mortality Including Polysubstance Overdose Deaths: A Randomized Clinical Trial.

Importance: The HEALing Communities Study (HCS) evaluated the effectiveness of the Communities That HEAL (CTH) intervention in preventing fatal overdoses amidst the US opioid epidemic.

Objective: To evaluate the impact of the CTH intervention on total drug overdose deaths and overdose deaths involving combinations of opioids with psychostimulants or benzodiazepines.

Design, Setting, And Participants: This randomized clinical trial was a parallel-arm, multisite, community-randomized, open, and waitlisted controlled comparison trial of communities in 4 US states between 2020 and 2023.

Use of fentanyl test strips by people who inject drugs: Baseline findings from the South Atlantic Fentanyl Test Strip Study (SAFTSS).

Background: Research published during the early fentanyl period exposed a growing concern of unwitting fentanyl exposure and a general willingness to use fentanyl test strips (FTS). A paucity of FTS studies over the last several years has restricted our ability to understand FTS use in the late fentanyl era. The South Atlantic FTS Study (SAFTSS) was established to investigate contemporaneous changes in FTS use and drug use behavior among a rural cohort of PWID.

Project Lifeline-II: Feasibility of Implementing Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Allegheny County, Pennsylvania.

Objectives: US community pharmacies are a unique and underused health service setting for identifying and potentially intervening with patients at risk of opioid overdose or opioid use disorder with evidence-based practices such as screening, brief intervention, and referral to treatment (SBIRT). The aim of our study was to assess the feasibility of implementing SBIRT in community pharmacies in an urban county in terms of engagement, reach, and equity across the cascade of pharmacy screening and care.

Methods: Patients aged 18 years or older receiving a schedule II or III opioid prescription at 1 of 17 participating community pharmacies in Allegheny County, Pennsylvania, were invited to engage in SBIRT as part of Project Lifeline-II from June 2020 through January 2023.

Epigenetics and the timing of neuronal differentiation.

Epigenetic regulation of the genome is required for cell-type differentiation during organismal development and is especially important to generate the panoply of specialized cell types that comprise the brain. Here, we review how progressive changes in the chromatin landscape, both in neural progenitors and in postmitotic neurons, orchestrate the timing of gene expression programs that underlie first neurogenesis and then functional neuronal maturation. We discuss how disease-associated mutations in chromatin regulators can change brain composition by impairing the timing of neurogenesis.

Healthcare expenditures for people with substance use disorders in drug courts compared to their peers in traditional courts.

Individuals within the criminal justice system are at greater risk of substance use-related morbidity and mortality and have substantial healthcare needs. In this quasi-experimental study, we assessed utilization patterns of Massachusetts Medicaid Program (MassHealth) services and associated expenditures among drug court probationers compared to a propensity score-matched sample of traditional court probationers. Risk of reoffending, employment status, age, and living arrangement data were used to calculate propensity scores and match probationers between the two court types, producing a final sample of 271 in each court (N=542).

Effect of the Communities that HEAL intervention on receipt of behavioral therapies for opioid use disorder: A cluster randomized wait-list controlled trial.

Background: The U.S. opioid overdose crisis persists.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

Aims: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems.

Methods: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346).

Reductions in World Health Organization Risk Drinking Level Are Associated With Reductions in Alcohol Use Disorder Diagnosis and Criteria: Evidence From an Alcohol Pharmacotherapy Trial.

Objectives: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria.

Methods: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346).

Cost of start-up activities to implement a community-level opioid overdose reduction intervention in the HEALing Communities Study.

Background: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e.

Reductions in WHO risk drinking levels correlate with alcohol craving among individuals with alcohol use disorder.

Background: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain.

Single-cell DNA methylation and 3D genome architecture in the human brain.

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures.

Establishing a Protocol for Determining the Costs of an Integrated Set of Evidence-based Practices Aimed at Reducing Opioid Overdose Deaths.

Objectives: In the midst of the opioid overdose crisis, local jurisdictions face a choice of public health interventions. A significant barrier when considering evidence-based practices (EBPs) is the lack of information regarding their implementation cost. This protocol paper provides the methodological foundation for the economic cost evaluations of community-wide strategies on the scale of a national study.

Associations between opioid overdose deaths and drugs confiscated by law enforcement and submitted to crime laboratories for analysis, United States, 2014-2019: an observational study.

Background: The overdose epidemic in the United States (US) continues to generate unprecedented levels of mortality. There is urgent need for a national data system capable of yielding high-quality, timely, and actionable information on existing and emerging drugs. Public health researchers have started using law enforcement forensic laboratory data to obtain surveillance information on illicit drugs.

Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures.

Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals.

Pennsylvania's Community Coordination Strategy to Reduce Opioid Overdose Deaths.

Objective: The Pennsylvania Opioid Overdose Reduction Technical Assistance Center (ORTAC) was developed to provide community-level support across Pennsylvania with the goal of reducing the opioid-related overdose death (ODD) rate via coalition building/coordination and tailored technical assistance. This study evaluates the initial effects of ORTAC engagement on county-level opioid ODD reductions.

Method: Using quasi-experimental difference-in-difference models, we compared ODD per 100,000 population per quarter between 2016 and 2019 in the 29 ORTAC-implementing counties against the 19 nonengaged counties while controlling for county-level time-varying confounders (e.

Association between law enforcement seizures of illicit drugs and drug overdose deaths involving cocaine and methamphetamine, Ohio, 2014-2019.

Background: The United States continues to experience a crisis of mounting opioid overdose deaths involving cocaine and methamphetamine (hereafter illicit stimulants). Law enforcement drug seizure data present a unique opportunity to examine the association between illicit-stimulant-involved overdose deaths (ISODs) and the illicit drug supply. Our objective is to better understand correlations between illicit drug market trends and increases in ISODs in Ohio in 2014-2019.

Rural and urban differences in undersupply of buprenorphine provider availability in the United States, 2018.

Background: Medications to treat opioid use disorder (OUD) including buprenorphine products are evidence-based and cost-effective tools for combating the opioid crisis. However, limited availability to buprenorphine is pervasive in the United States (US) and may serve to exacerbate the deadly epidemic. Although prior research points to rural counties as especially needy of strategies that improve buprenorphine availability, it is important to investigate the availability of waivered providers according to treatment need as defined by the county-level rate of opioid-overdose deaths (OOD).

The Relationship Between Reductions in WHO Risk Drinking Levels During Treatment and Subsequent Healthcare Costs for the ACTIVE Workgroup.

Background: Abstinence has historically been considered the target outcome for alcohol use disorder (AUD) treatment, yet recent work has found drinking reductions after AUD treatment, as measured by World Health Organization (WHO) risk drinking levels, are associated with meaningful improvements in functioning, physical health, and quality of life.

Objectives: This study extends previous analyses of AUD treatment outcomes by estimating the association between changes in WHO risk drinking levels (very high, high, medium, and low, based on average daily alcohol consumption) and healthcare costs.

Methods: Secondary data analysis of the COMBINE study, a multisite randomized clinical trial of acamprosate, naltrexone and behavioral interventions for AUD.

Mutations of the histone linker H1-4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4.

Rahman syndrome (RMNS) is a rare genetic disorder characterized by mild to severe intellectual disability, hypotonia, anxiety, autism spectrum disorder, vision problems, bone abnormalities and dysmorphic facies. RMNS is caused by de novo heterozygous mutations in the histone linker gene H1-4; however, mechanisms underlying impaired neurodevelopment in RMNS are not understood. All reported mutations associated with RMNS in H1-4 are small insertions or deletions that create a shared frameshift, resulting in a H1.

Individual and Community Social Determinants of Health and Recovery from Alcohol Use Disorder Three Years following Treatment.

Prior research on recovery from alcohol use disorder (AUD) has often focused on individual-level factors that promote recovery. Given systemic health inequities, it is also important to study community-level social determinants of health (SDOH) that may promote recovery from AUD. This study extended prior work examining individual profiles of recovery from AUD to assess how individual and community SDOH at the time of treatment entry were associated with recovery from AUD three years after treatment.