A state-wide education program on opioid use disorder: influential community members\u27 knowledge, beliefs, and opportunities for coalition development

Background: Deep South states, particularly Alabama, experience disproportionately higher opioid prescribing rates versus national rates. Considering limited opioid use disorder (OUD) providers in this region, collaborative efforts between non-healthcare professionals is critical in mitigating overdose mortality. The Alabama Opioid Training Institute (OTI) was created in 2019 to empower community members to take action in combatting OUD in local regions. The OTI included: 1) eight full-day in-person conferences; and 2) an interactive mobile-enabled website ( https://alabamaoti.org ). This study assessed the impact of the OTI on influential community members\u27 knowledge, abilities, concerns, readiness, and intended actions regarding OUD and opioid overdose mitigation. Methods: A one-group prospective cohort design was utilized. Alabama community leaders were purposively recruited via email, billboards, television, and social media advertisements. Outcome measures were assessed via online survey at baseline and post-conference, including: OUD knowledge (percent correct); abilities, concerns, and readiness regarding overdose management (7-point Likert-type scale, 1 = strongly disagree to 7 = strongly agree); and actions/intended actions over the past/next 6 months (8-item index from 0 to 100% of the time). Conference satisfaction was also assessed. Changes were analyzed using McNemar or Marginal Homogeneity tests for categorical variables and two-sided paired t-tests for continuous variables (alpha = 0.05). Results: Overall, 413 influential community members participated, most of whom were social workers (25.7%), female (86.4%), and White (65.7%). Community members\u27 OUD knowledge increased from mean [SD] 71.00% [13.32] pre-conference to 83.75% [9.91] post-conference (p \u3c 0.001). Compared to pre-conference, mean [SD] ability scale scores increased (3.72 [1.55] to 5.15 [1.11], p \u3c 0.001) and concerns decreased (3.19 [1.30] to 2.64 [1.17], p \u3c 0.001) post-conference. Readiness was unchanged post-conference. Attendees\u27 intended OUD-mitigating actions in the next 6 months exceeded their self-reported actions in the past 6 months, and 92% recommended the OTI to others. Conclusions: The Alabama OTI improved community leaders\u27 knowledge, abilities, and concerns regarding OUD management. Similar programs combining live education and interactive web-based platforms can be replicated in other states

Third-Party Fecal Microbiota Transplantation for High-Risk Treatment-Naïve Acute GVHD of the Lower Gi Tract

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

The Moderating Power of Impulsivity: A Systematic Literature Review Examining the Theory of Planned Behavior

The theory of planned behavior (TPB) states that behavioral intention is the best predictor of actual behavior change. However, intention explains only a portion of the variance in behavior. Of specific interest is the question of which moderating or mediating variables can be leveraged to aid health promotion interventions utilizing the tenets of behavioral economics (delay discounting and commitment contracts) in the intention–behavior pathway. Impulsivity has been postulated to fill this role and may be applied to multiple behaviors. We aim to determine if impulsivity moderates the association between intention and actual behavior in the TPB, to discover what other variables may moderate or mediate this association, and to apply the findings to future studies in the field of behavioral economics. To this end, a systematic review was conducted using the PubMed, PsychINFO, and Embase online databases. Eligible studies in peer-reviewed journals published prior to November 2021 were selected. Thirty-three studies were included in the final review, examining physical activity, diet, preventive health, mental health, addiction, and medication adherence behaviors. Three main concepts emerged: (1) impulsivity moderates the association between intention and behavior change; (2) self-efficacy moderates the association between intention and behavior change; and (3) planning and self-efficacy contribute to moderated mediation. This review demonstrates a gap in the literature regarding the application of the TPB to the intention–behavior pathway for health behaviors. Future studies in behavioral economics may leverage the variables of impulsivity, self-efficacy, and planning to predict follow-through in this area and to develop targeted change initiatives

Public Perceptions of Community Pharmacy-Based Naloxone Services: A National Cross-Sectional Survey

Little is known about the general public’s perceptions regarding community pharmacist-delivered naloxone services at the national level. Accordingly, the purpose of this study was to describe the US general public’s awareness, knowledge, beliefs, comfort, perceived barriers, abilities, and communication preferences related to community pharmacy-based naloxone services. A national, online cross-sectional survey was conducted in September 2021 among US adults ≥18 years recruited via Amazon Mechanical Turk (MTurk). Primary outcome measures were assessed via 5-point Likert-type scales, including: (1) naloxone awareness and knowledge; (2) naloxone beliefs; (3) comfort with pharmacist-provided naloxone; (4) perceived barriers to pharmacy-based naloxone; (5) opioid overdose competencies, concerns, and readiness; and (6) preferred pharmacist-patient naloxone communication strategy. Analyses included descriptive statistics and logistic regression models to assess predictors of preferred communication strategies. Of 301 respondents, 82.1% were White, 48.8% female, and mean 43 years. Eighty-five percent were unaware of pharmacy-provided naloxone and mean [SD] knowledge score was low (29.3% [16.8]). Mean [SD] beliefs (3.78 [0.61]) and comfort (3.70 [0.54]) were positive, while perceived barriers were low/neutral (2.93 [0.78]). For communication, 54% preferred general advertisement, 32.9% universal offer, and 13.3% targeted offer. The odds of preferring a general advertisement or universal offer over a targeted offer increased with greater awareness (AOR:4.52; p = 0.003) and comfort (AOR:3.79; p = 0.003), and decreased with greater competence (AOR:0.35; p = 0.001). Although awareness and knowledge regarding community pharmacy-based naloxone services was low, beliefs and comfort were positive and perceived barriers were low/neutral. General or universal offers of naloxone were preferred over targeted approaches. Future studies should test the impact of communication strategies on naloxone uptake

Organizational Readiness to Implement Community Pharmacy-Based Opioid Counseling and Naloxone Services: A Scoping Review of Current Practice Models and Opportunities

The purpose of this study was to explore existing practice models and opportunities surrounding community pharmacist-delivered opioid counseling and naloxone (OCN) services in the U.S., with the goal of enhancing organizational readiness and improving patient access. A scoping literature review was conducted. English-language articles published in peer-reviewed journals from January 2012–July 2022 were sought via PubMed, CINAHL, IPA, and Google Scholar using permutations of terms such as “pharmacist/pharmacy”, “opioid/opiate”, “naloxone”, “counseling”, and “implement/implementation”. Original articles reporting the resources/inputs (personnel; pharmacist full-time equivalents; facilities and expenses; in-house versus outsourced personnel), implementation processes (legal source of pharmacist authority; patient identification strategies; intervention procedures; workflow strategies; business operations), and programmatic outcomes (uptake and delivery; interventions made; economic impact; patient or provider satisfaction) of pharmacist-delivered OCN services in community (retail) settings were retained. Twelve articles describing ten unique studies were included. The studies primarily used quasi-experimental designs and were published from 2017 to 2021. The articles described seven broad program elements/themes: interprofessional collaboration (n = 2); patient education format including one-on-one patient education (n = 12) and group education sessions (n = 1); non-pharmacist provider education (n = 2); pharmacy staff education (n = 8); opioid misuse screening tools (n = 7); naloxone recommendation/dispensing (n = 12); and opioid therapy and pain management (n = 1). Pharmacists screened/counseled 11–2716 patients and provided 11–430 doses of naloxone. Limited implementation costs, patient/provider satisfaction, or economic impact measures were reported. This review may serve as a guide for community pharmacists in implementing OCN services in their own practices. Future studies should clarify OCN program implementation costs, patient/provider satisfaction, and the economic impact