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Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P

Introduction: Clinical trial recruitment and retention of individuals who use substances are challenging in any setting and can be particularly difficult in emergency department (ED) settings. This article discusses strategies for optimizing recruitment and retention in substance use research conducted in EDs.Methods: Screening, Motivational Assessment, Referral, and Treatment in Emergency Departments (SMART-ED) was a National Drug Abuse Treatment Clinical Trials Network (CTN) protocol designed to assess the impact of a brief intervention with individuals screening positive for moderate to severe problems related to use of non-alcohol, non-nicotine drugs. We implemented a multisite, randomized clinical trial at six academic EDs in the United States and leveraged a variety of methods to successfully recruit and retain study participants throughout the 12-month study course. Recruitment and retention success is attributed to appropriate site selection, leveraging technology, and gathering adequate contact information from participants at their initial study visit.Results: The SMART-ED recruited 1,285 adult ED patients and attained follow-up rates of 88%, 86%, and 81% at the 3-, 6-, and 12-month follow-up periods, respectively. Participant retention protocols and practices were key tools in this longitudinal study that required continuous monitoring, innovation, and adaptation to ensure strategies remained culturally sensitive and context appropriate through the duration of the study.Conclusion: Tailored strategies that consider the demographic characteristics and region of recruitment and retention are necessary for ED-based longitudinal studies involving patients with substance use disorders.

This paper describes the first implementation of the Δx = 3.25 km version of the Energy Exascale Earth System Model (E3SM) global atmosphere model and its behavior in a 40-day prescribed-sea-surface-temperature simulation (January 20 through February 28, 2020). This simulation was performed as part of the DYnamics of the Atmospheric general circulation Modeled On Non-hydrostatic Domains (DYAMOND) Phase 2 model intercomparison. Effective resolution is found to be (Formula presented.) the horizontal dynamics grid resolution despite using a coarser grid for physical parameterizations. Despite this new model being in an immature and untuned state, moving to 3.25 km grid spacing solves several long-standing problems with the E3SM model. In particular, Amazon precipitation is much more realistic, the frequency of light and heavy precipitation is improved, agreement between the simulated and observed diurnal cycle of tropical precipitation is excellent, and the vertical structure of tropical convection and coastal stratocumulus look good. In addition, the new model is able to capture the frequency and structure of important weather events (e.g., tropical cyclones, extratropical cyclones including atmospheric rivers, and cold air outbreaks). Interestingly, this model does not get rid of the erroneous southern branch of the intertropical convergence zone nor the tendency for strongest convection to occur over the Maritime Continent rather than the West Pacific, both of which are classic climate model biases. Several other problems with the simulation are identified, underscoring the fact that this model is a work in progress.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P

In this article, we demonstrate the potential of machine learning approaches as inductive analytic tools for expanding our current evidence base for policy making and practice that affects people with intellectual and developmental disabilities (IDD). Using data from the National Core Indicators In-Person Survey (NCI-IPS), a nationally validated annual survey of more than 20,000 nationally representative people with IDD, we fit a series of classification tree and random forest models to predict individuals' employment status and day activity participation as a function of their responses to all other items on the 2017-2018 NCI-IPS. The most accurate model, a random forest classifier, predicted employment outcomes of adults with IDD with an accuracy of 89 percent on the testing sample, and 80 percent on the holdout sample. The most important variable in this prediction was whether or not community employment was a goal in this person's service plan. These results suggest the potential machine learning tools to examine other valued outcomes used in evidence-based policy making to support people with IDD.

This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission-relevant water cycle questions. Its components include atmosphere and land (110-km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP-class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP-class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two-layer energy balance model, we attribute this divergence to the model's strong aerosol-related effective radiative forcing (ERFari+aci = −1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).

A nuanced understanding of disparities impacting racialized people with intellectual and developmental disabilities (IDD) requires scholars employ research methods that make visible the structural factors that influence outcomes. Following the work of Tukufu Zuberi and Eduardo Bonilla-Silva, we explore race-based methodological considerations for disparities research with Black people with IDD. Specifically, we discuss (a) structural racism in research methods, employing disability critical race theory as a framework, (b) the absence of Black voices and Black scholarship, (c) the abstraction and misuse of race as a variable, and (d) mapping race as a point of discussion in the IDD discourse. Implications for research are discussed and recommendations for contextualizing race, ensuring equity in representation and dissemination, and amplifying the voices of Black scholars are provided.

Vietnam ratified the United Nations Convention on the Rights of Persons with Disabilities (CRPD) in 2015, signalling a commitment to the basic human rights of citizens with disabilities. Previous research has shown people with disabilities in Vietnam to be marginalised in society, often with limited educational or work opportunity, and with limited financial means. Using in-depth semi-structured interviews conducted in Vietnam and a thematic analysis approach to data interpretation, this article examines the current status of people with disabilities in Vietnam in relation to the core elements of the CRPD, from the perspectives of people with disabilities, their families, and professionals who support them. Findings suggest that, while Vietnamese society has made strides supporting people with disabilities, work remains to be done for the country to comply with the CRPD's core principles. Suggestions for future action are offered, including ways to support human rights of people with disabilities within cultural contexts.

People with intellectual and developmental disabilities (IDD) often rely on Medicaid-funded services and supports to facilitate their daily living. The financial investment for these services is significant, yet little work has been conducted to understand how these investments affect life outcomes. This pilot study used a novel data integration approach to offer initial insights about how Medicaid expenditures relate to outcomes using Medicaid claims data, results of the National Core Indicators consumer survey, and data from the Supports Intensity Scale (SIS). Findings suggested that subpopulations of people with IDD who also had high behavioral needs or high medical needs had significantly higher expenditures than individuals with more typical SIS-assessed support needs. Regression analyses suggested mixed outcomes based on the factors we considered, including a finding that people with IDD who lived in sponsored residential care homes were more likely to engage in inclusive activities in the community than those who lived in larger congregate settings, or those who lived in a family home. Results of this pilot, when brought to scale, will be useful in examining the performance of state IDD service systems over time.

Case management (CM) is one of the most commonly used services by individuals with intellectual and developmental disabilities (IDD), but little is known about the workers who provide CM. This study used a mixed methods approach to gain understanding of the CM workforce in one U.S. state. An online survey was completed by 35 IDD service directors (87.5% of directors in the state); and 113 CMs and CM supervisors participated in semistructured interviews and focus groups. Results indicated an annual crude separation rate of 28.2%, and participants often complained that turnover resulted in caseload sizes that prevented optimal outcomes for people with IDD. A limited applicant pool, duties focused on regulatory compliance, and inadequate wages were cited as major challenges for CMs.

Self-directed home and community based services (HCBS) waiver services and supports for people with intellectual and developmental disabilities (IDD) have become a viable and widely used method of service provision in the United States. Grounded in theories of self-determination, previous literature on self-direction has suggested high satisfaction and positive outcomes for people who use self-directed programs as well as cost savings for state IDD service systems. This study explored the ways in which state IDD service administrators think about how self-direction may be used as a method of achieving cost savings while providing opportunities for people with IDD and their families to exercise choice and control. Informed by 54 high-level IDD service administrators in 34 states, and guided by a thematic analysis approach to data interpretation, the study found evidence that administrators typically see strong potential for self-direction to have cost-savings benefits, while also fostering choice. In the current political climate, the need for cautious fiscal stewardship may become a stronger driving force behind self-direction for people with IDD in the United States.

Families of children with autism spectrum disorder (ASD) play a central role in selecting interventions for their children. Despite the importance of understanding the factors that motivate early decisions about treatment, the literature has concentrated little attention on how and why parents of young children with ASD make decisions about services and supports. Using a collective case study design informed by a diverse sample, this study found a heavy reliance on formal and informal sources of support in guiding parents' early treatment decisions for their young children with ASD. The Internet also served as a primary source of informational support to families. Findings highlight the importance of family support initiatives including peer-to-peer family mentoring and decision support aides to assist families in critically evaluating online and print information regarding ASD.

The new generation of heterogeneous CPU/GPU computer systems offer much greater computational performance but are not yet widely used for climate modeling. One reason for this is that traditional climate models were written before GPUs were available and would require an extensive overhaul to run on these new machines. In addition, even conventional "high–resolution" simulations don't currently provide enough parallel work to keep GPUs busy, so the benefits of such overhaul would be limited for the types of simulations climate scientists are accustomed to. The vision of the Simple Cloud‐Resolving Energy Exascale Earth System (E3SM) Atmosphere Model (SCREAM) project is to create a global atmospheric model with the architecture to efficiently use GPUs and horizontal resolution sufficient to fully take advantage of GPU parallelism. After 5 years of model development, SCREAM is finally ready for use. In this paper, we describe the design of this new code, its performance on both CPU and heterogeneous machines, and its ability to simulate real‐world climate via a set of four 40 day simulations covering all 4 seasons of the year. Plain Language Summary: This paper describes the design and development of a 3 km version of the Energy Exascale Earth System Model (E3SM) atmosphere model, which has been fully rewritten in C++ using the Kokkos library for performance portability. This newly rewritten model is able to take advantage of the state–of–the–science high performance computing systems which use graphical processor units (GPUs) to mitigate much of the computational expense which typically plagues high–resolution global modeling. Taking advantage of this high–performance we are able to run four seasons of simulations at 3 km global resolution. We discuss the biases, including the diurnal cycle, by comparing model results with satellite and Atmospheric Radiation Measurement ground‐based site data. Key Points: Describes the C++/Kokkos implementation of the Simple Cloud–Resolving E3SM Atmosphere Model (SCREAMv1)SCREAMv1 leverages GPUs to surpass one simulated year per compute day at global 3 km resolutionHigh resolution improves some meso‐scale features and the diurnal cycle but large‐scale biases require improvement across all four seasons [ABSTRACT FROM AUTHOR]

This study examines marine boundary layer cloud regime transition during a cold air outbreak (CAO) over the Norwegian Sea, simulated by a global storm‐resolving model (GSRM) known as the Simple Cloud‐Resolving Energy Exascale Earth System Model Atmosphere Model (SCREAM). By selecting observational references based on a combination of large‐scale conditions rather than strict time‐matched comparisons, this study finds that SCREAM qualitatively captures the CAO cloud transition, including boundary layer growth, cloud mesoscale structure, and phase partitioning. SCREAM also accurately locates the greatest ice and liquid in the mesoscale updrafts, however, underestimates supercooled liquid water in cumulus clouds. The model evaluation approach adopted by this study takes advantages of the existing computational‐expensive global simulations of GSRM and the available observations to understand model performance and can be applied to assessments of other cloud regimes in different regions. Such practice provides valuable guidance on the future effort to correct and improve biased model behaviors. Plain Language Summary: Cold air outbreaks occur when cold, dry air moves over warmer ocean regions, forming extensive boundary layer clouds. However, current climate models struggle to accurately represent these clouds due to their complex nature. This study examines the performance of the global storm‐resolving model, the Simple Cloud‐Resolving Energy Exascale Earth System Model Atmosphere Model (SCREAM), in simulating marine boundary layer clouds during cold air outbreaks over the Norwegian Sea. This study compares the SCREAM simulated clouds during a cold air outbreak event to observations under similar large‐scale conditions from satellites and ground‐based measurements collected during a field campaign of the Atmospheric Radiation Measurement program. The results indicate that SCREAM successfully simulates three distinct cloud patterns during cold air outbreaks with credible mesoscale structures. Yet, it tends to underestimate supercooled liquid water and consequently, the cloud liquid water fraction, especially in cumulus clouds. The study suggests that using high‐resolution observations under similar large‐scale conditions can effectively evaluate global storm‐resolving models. This approach helps identify areas for improvement without requiring expensive global storm‐resolving model simulation designed for specific cases. Key Points: The Simple Cloud‐Resolving Energy Exascale Earth System Model Atmosphere Model (SCREAMv0), at a resolution of 3 km, simulated three distinctive cloud regimes in cold air outbreaks with credible mesoscale structuresSCREAMv0 qualitatively captures the transition of the cloud phase partitioning based on high‐resolution observationsObservations selected based on similar large‐scale conditions can be important references for global storm‐resolving model evaluation [ABSTRACT FROM AUTHOR]

Turnover among direct support professionals (DSPs) in community support settings for individuals with intellectual and developmental disabilities (IDD) has been regarded as a challenge since tracking of this workforce began in the 1980s. This study utilized a group randomized controlled design to test the effects of a competency-based training intervention for DSPs on site-level turnover rates over a one year period. Results suggested that, compared with the control group, sites receiving the training intervention experienced a significant decrease in annual turnover, when multiple factors were controlled. Implications, including the importance of considering quality training as a long term organizational investment and intervention to reduce turnover, are discussed.

Objective: The primary aim of this qualitative study was to delineate psychological mechanisms of change in the first randomized controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder (AUD). Theories regarding psychological processes involved in psychedelic therapy remain underdeveloped. Method: Participants (N = 13) mostly identified as non-Hispanic and White, with approximately equal proportions of cisgender men and women. Participants engaged in semistructured interviews about their subjective experiences in the study. Questions probed the nature of participants' drinking before and after the study as well as coping patterns in response to strong emotions, stress, and cravings for alcohol. Verbatim transcripts were coded using Dedoose software, and content was analyzed with interpretive phenomenological analysis. Results: Participants reported that the psilocybin treatment helped them process emotions related to painful past events and helped promote states of self-compassion, self-awareness, and feelings of interconnectedness. The acute states during the psilocybin sessions were described as laying the foundation for developing more self-compassionate regulation of negative affect. Participants also described newfound feelings of belonging and an improved quality of relationships following the treatment. Conclusion: Our results support the assertion that psilocybin increases the malleability of self-related processing, and diminishes shame-based and self-critical thought patterns while improving affect regulation and reducing alcohol cravings. These findings suggest that psychosocial treatments that integrate selfcompassion training with psychedelic therapy may serve as a useful tool for enhancing psychological outcomes in the treatment of AUD. Public Health Significance Statement This study demonstrated the importance of psychological factors that influence outcomes in psilocybinassisted therapy for alcohol use disorder (AUD). Our findings suggest that psilocybin treatment prompted meaningful and enduring improvements in self-compassion and affect regulation. These psychological processes may help individuals with AUD cope with difficult emotions and stress and prevent relapse by encouraging adaptive coping responses. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this article was to explore student perspectives regarding effective preceptors with the intention to improve development of supervised clinical practice experiences. Methods In total, 136 clinical year physician assistant (PA) students, representing 9 accredited PA programs, participated in a mixed-methods survey, including a 5-point Likert scale to identify characteristics of an effective preceptor. The survey achieved a 36.2% response rate. Quantitative data were analyzed based on mean and standard deviation (SD) with the analysis of variance to promote generalizability. Thematic analysis was performed on qualitative responses. Results Students reported the highest level of agreement that an effective preceptor welcomes questions from the student (mean 4.88, SD 0.54), are enthusiastic about having a student (4.84, 0.52), and provide a welcoming support staff who encourages student education (4.71, 0.66). Students also highlighted the positive effect of preceptor engagement during clinical rotations. Conclusion A preceptor who actively engages their student has the greatest positive impact on clinical education. Preceptors can implement clinical teaching strategies from this article to improve student-perceived effectiveness of their rotation. [ABSTRACT FROM AUTHOR]

Self-directed programs that allow individuals with intellectual and developmental disabilities to exercise greater control over their finances have become increasingly common in recent years. At the same time, challenges in the recruitment, retention, and training of direct support workers in the field have grown more acute. In this article, the authors investigate the status of the direct support workforce for people using self-directed supports in 1 Midwestern state, based on the results of a statewide survey of service users. Although additional research is needed, the results of this study suggest that people who use self-directed funding options are satisfied with their ability to direct staffing, though challenges remain. Among these challenges, the presence of higher than expected wages but lower than expected benefits provision compared with traditional services may have serious policy and staff retention ramifications that affect the long-term viability of self-directed funding options. In addition, staff training remains a challenge, with service users in this sample reporting low rates of training beyond a general skill set. Implications of these findings are discussed.

Future life planning is a growing concern among families with children with disabilities. This article presents a needs assessment evaluating feasibility of a new model for future life planning for family caregivers, Lifetime Assistance, which will provide ongoing planning and monitoring for individuals with intellectual and developmental disabilities. Using surveys informed by a series of focus groups, data were gathered from older and younger parents in one midwestern state regarding the potential program. Study results indicate that respondents did not feel the current system of support was adequate for planning for their child's future, nor sufficient for monitoring the quality of life for their children in the future. Although almost all families had identified a person to support their family members when they were no longer able to do so, parental caregivers overwhelmingly identified the need for the Lifetime Assistance program and many were willing to pay for this service themselves. (Contains 5 tables.)

INTRODUCTION: Continuous aerosolized β2 agonist, namely albuterol, is the most commonly used therapy for critical asthma. Benzalkonium chloride is a preservative present in some formulations of aerosolized albuterol solutions that can induce bronchospasm. Recent studies have shown that inhalation of albuterol containing benzalkonium chloride might induce unintended bronchoconstriction and poor outcomes. This study aimed to investigate whether using albuterol solutions containing benzalkonium chloride results in prolonged hospital length of stay (LOS). METHODS: This was a retrospective cohort study of pediatric subjects admitted to the pediatric ICU (PICU) and treated with continuous albuterol. Data were collected and compared before and after a change to benzalkonium chloride--containing solutions. Subjects who were treated with preservative-free solutions were used as control. The primary outcome was PICU and hospital LOS; secondary outcomes included the duration of continuous albuterol and use of adjunctive therapies. RESULTS: A total of 266 admissions were included in the study. One hundred forty subjects (52.6%) were exposed to benzalkonium chloride. Median age and severity of illness scoring were similar between groups. The initial dose of continuous albuterol was significantly higher in the benzalkonium chloride group (median 15 interquartile range [IQR] 10--20 mg/h) compared to the preservative-free group (median 10 IQR 10--20 mg/h) (P < .001). PICU LOS was longer for the preservative-free group, 2.5 (IQR 1.4--4.6) d vs 1.8 (IQR 1.1--2.9) d for benzalkonium chloride group (P = .002). There was no significant difference in duration of continuous albuterol therapy (P = .16) or need for adjunctive respiratory support (heliox [P 5 .32], noninvasive ventilation [P = .81], and invasive mechanical ventilation [P = .57]). CONCLUSIONS: In contrast to published literature showing that benzalkonium chloride may be associated with a longer duration of continuous albuterol nebulization and hospital LOS, our study demonstrated that benzalkonium chloride--containing albuterol is safe for continuous nebulization in critically ill children and not associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Surveyed students at two different academic institutions to understand students' perceptions of ethical job-search behavior and to assess relationship of institution type to students' evaluations of ethical dilemmas. Results suggest that significant number of students were unaware of ethical nature of some job-search situations and implications of their decisions. Students also lacked understanding of inappropriate behaviors. (NB)

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines.Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications.Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD. [ABSTRACT FROM AUTHOR]

Importance: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.Objective: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.Design, Setting, and Participants: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD.Interventions: Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy.Main Outcomes and Measures: The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance.Results: A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin.Conclusions and Relevance: Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD.Trial Registration: ClinicalTrials.gov Identifier: NCT02061293. [ABSTRACT FROM AUTHOR]

Aims: To investigate among older adults with DSM-5 alcohol use disorder (AUD) the relevance of (1) baseline DSM-5 AUD severity, (2) age of DSM-5 AUD onset, and (3) the interactions of DSM-5 AUD severity*treatment condition and age of DSM-5 AUD onset*treatment condition for the prediction of AUD treatment outcomes. Methods: The international multicenter RCT "ELDERLY-Study" compared outpatient motivational enhancement therapy (4 sessions) with outpatient motivational enhancement therapy followed by community reinforcement approach for seniors (8 sessions) in adults aged 60+ with DSM-5 AUD. Baseline and 1-, 3-, and 6-month follow-up data from the German and Danish ELDERLY-sites (n = 544) were used (6-month participation rate: 75.9%). DSM-5 AUD diagnoses were obtained using the Mini International Neuropsychiatric Interview and alcohol use using Form 90. Associations between DSM-5 AUD severity and age of onset and AUD treatment outcomes were investigated using multiple logistic regression and generalized linear models. Results: The sample was diverse in AUD severity (severe: 54.9%, moderate: 28.2%, mild: 16.9%) and age of onset (median: 50 years; 12–78 years). Overall, with few exceptions, neither AUD severity, nor age of onset, nor their respective interactions with treatment condition significantly predicted drinking outcomes at the different follow-ups (P ≥ 0.05). Conclusions: No indication was found for the need to tailor treatment content according to DSM-5 AUD severity and earlier onset in older adults. [ABSTRACT FROM AUTHOR]