Faculty Bibliography

Importance/UNASSIGNED:Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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, 5 (5.3%) were Black, 16 (16.8%) 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/UNASSIGNED: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/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02061293.

Varicoceles are an abnormal dilation of the pampiniform plexus within the spermatic cord that can impair spermatogenesis and testosterone production in the testes through a variety of theorized mechanisms. Nearly 15% of the male population is affected by varicocele, though most men are entirely asymptomatic. Among men presenting with infertility, the incidence of varicocele has been observed to be as high as 35-40%. Varicoceles are the most commonly identified abnormalities in men presenting with infertility, and, when associated with abnormal semen parameters, present the urologist with an opportunity for intervention. Serum testosterone levels have been demonstrated to be lower on average among patients with varicoceles and data have suggested that varicocelectomy improves mean serum testosterone levels postrepair. Nonetheless, there are no current guideline indications for varicocelectomy for men with symptomatic hypogonadism, and it is not yet known whether the reported improvement in serum testosterone with surgical intervention is clinically meaningful. In this review, we discuss the most up-to-date literature on the mechanisms by which varicoceles are purported to impair both spermatogenesis and testosterone production as well as the effect of varicocelectomy on serum testosterone levels.

OBJECTIVES:To determine the association between individual, network, and structural COVID-19-related stressors and changes in sleep duration and quality among Black cisgender sexual minority men (SMM) and Black transgender women during the COVID-19 peak infectivity rate in Chicago. METHODS:From April 20, 2020 to July 31, 2020, we conducted the N2 COVID Study in Chicago (n = 226). The survey included questions regarding multi-level COVID-19-related stressors (eg, food unavailability, partner violence, housing instability, concern about neighborhood COVID-19), sleep duration, and sleep quality. RESULTS:About 19.5% of our sample reported a shorter duration of sleep during the initial peak COVID-19 infectivity, while 41.2% reported more sleep and 38.9% reported about the same. Compared to the prepandemic period, 16.8% reported that their sleep quality worsened in the COVID-19 pandemic, while 27.9% reported their sleep quality had improved and 55.3% reported it was about the same. In multivariable models, we found that ≥1 day of physical stress reaction, worrying about being infected with COVID-19, traveling during COVID-19 being a financial burden, not having enough medication, knowing someone who was diagnosed with COVID-19, partner violence and housing instability were associated with poor sleep health in the COVID-19 pandemic (adjusted risk ratio: 1.82-3.90, p < .05). CONCLUSIONS:These data suggest that COVID-19-related stressors impacted poor sleep duration and quality during the pandemic among this cohort. Multi-level interventions to reduce COVID-19-related stressors (eg, meditation, intimate partner violence prevention and housing programs) may be useful for improving sleep health among Black cisgender sexual minority men and Black transgender women.

Morbidity and mortality from COVID-19 have unduly affected older adults from racial and ethnic minority groups. In this article, we highlight the experiences and vulnerabilities of diverse older adults with complex health and social needs when their access to vital, but overlooked, community-based adult day service centers (ADSCs) was abruptly cut off during a pandemic. Pandemic-related ADSC closures left vulnerable older adults and their care partners without essential daily support and services, such as health monitoring and socialization. However, the magnitude of the impact of ADSC closures on well-being, particularly among members of racial/ethnic minority groups, has yet to be measured with any form of "big data" because large-scale, nationally representative data sets consisting of participant-level information and outcomes associated with ADSC participation do not yet exist. Unmet needs of older adults resulting from pandemic-related ADSC closures are underrecognized because of a lack of systematic data collection, undermining efforts to achieve health equity. We call on ADSCs to link rigorous collection of racial and ethnic data to quality measures of access to equitable "age-friendly" care as a means of better supporting diverse community-dwelling older adults beyond the COVID-19 pandemic. (Am J Public Health. 2022;112(10):1421-1428. https://doi.org/10.2105/AJPH.2022.306968).

OBJECTIVE:Midlife vascular risk factors (MVRFs) are associated with incident dementia, as are amyloid β (Aβ) deposition and neurodegeneration. Whether vascular and Alzheimer disease-associated factors contribute to dementia independently or interact synergistically to reduce cognition is poorly understood. METHODS:Participants in the Atherosclerosis Risk in Communities-Positron Emission Tomography study were followed from 1987-1989 (45-64 years old) through 2016-2017 (74-94 years old), with repeat cognitive assessment and dementia adjudication. In 2011-2013, dementia-free participants underwent brain magnetic resonance imaging (with white matter hyperintensity [WMH] and brain volume measurement) and florbetapir (Aβ) positron emission tomography. The relative contributions of vascular risk and injury (MVRFs, WMH volume), elevated Aβ standardized uptake value ratio (SUVR), and neurodegeneration (smaller temporoparietal brain regions) to incident dementia were evaluated with adjusted Cox models. RESULTS:In 298 individuals, 36 developed dementia (median follow-up = 4.9 years). Midlife hypertension and Aβ each independently predicted dementia risk (hypertension: hazard ratio [HR] = 2.57, 95% confidence interval [CI] = 1.16-5.67; Aβ SUVR [per standard deviation (SD)]: HR = 2.57, 95% CI = 1.72-3.84), but did not interact significantly, whereas late life diabetes (HR = 2.50, 95% CI = 1.18-5.28) and Aβ independently predicted dementia risk. WMHs (per SD: HR = 1.51, 95% CI = 1.03-2.20) and Aβ SUVR (HR = 2.52, 95% CI = 1.83-3.47) independently contributed to incident dementia, but WMHs lost significance when MVRFs were included. Smaller temporoparietal brain regions were associated with incident dementia, independent of Aβ and MVRFs (HR = 2.18, 95% CI = 1.18-4.01). INTERPRETATION:Midlife hypertension and late life Aβ are independently associated with dementia risk, without evidence for synergy on a multiplicative scale. Given the independent contributions of vascular and amyloid mechanisms, multiple pathways should be considered when evaluating interventions to reduce the burden of dementia. ANN NEUROL 2022;92:607-619.

INTRODUCTION/UNASSIGNED:The learning health system (LHS) aligns science, informatics, incentives, stakeholders, and culture for continuous improvement and innovation. The Agency for Healthcare Research and Quality and the Patient-Centered Outcomes Research Institute designed a K12 initiative to grow the number of LHS scientists. We describe approaches developed by 11 funded centers of excellence (COEs) to promote partnerships between scholars and health system leaders and to provide mentored research training. METHODS/UNASSIGNED:Since 2018, the COEs have enlisted faculty, secured institutional resources, partnered with health systems, developed and implemented curricula, recruited scholars, and provided mentored training. Program directors for each COE provided descriptive data on program context, scholar characteristics, stakeholder engagement, scholar experiences with health system partnerships, roles following program completion, and key training challenges. RESULTS/UNASSIGNED:To date, the 11 COEs have partnered with health systems to train 110 scholars. Nine (82%) programs partner with a Veterans Affairs health system and 9 (82%) partner with safety net providers. Clinically trained scholars (n = 87; 79%) include 70 physicians and 17 scholars in other clinical disciplines. Non-clinicians (n = 29; 26%) represent diverse fields, dominated by population health sciences. Stakeholder engagement helps scholars understand health system and patient/family needs and priorities, enabling opportunities to conduct embedded research, improve outcomes, and grow skills in translating research methods and findings into practice. Challenges include supporting scholars through roadblocks that threaten to derail projects during their limited program time, ranging from delays in access to data to COVID-19-related impediments and shifts in organizational priorities. CONCLUSIONS/UNASSIGNED:Four years into this novel training program, there is evidence of scholars' accomplishments, both in traditional academic terms and in terms of moving along career trajectories that hold the potential to lead and accelerate transformational health system change. Future LHS training efforts should focus on sustainability, including organizational support for scholar activities.

BACKGROUND:Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited. AIMS/OBJECTIVE:To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs). RESULTS:Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, p < 0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation. CONCLUSION/CONCLUSIONS:Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.

BACKGROUND/UNASSIGNED:fetal growth trajectories and assessed whether maternal stress modified these associations. METHODS/UNASSIGNED:= 833 scans, GA range 10-42 weeks, mean 2.4 scans/participant). Adjusted linear mixed models with a GA quadratic growth curve were used for each PFAS exposure and growth outcome. PFOS and PFHxS were modeled continuously (100% sample detection), while PFOA, PFNA, and PFDA were modeled categorically (57-70% sample detection). Scores on the Perceived Stress Scale (PSS) measured in pregnancy were dichotomized at the median (<13 vs. ≥ 13) in stratified models. RESULTS/UNASSIGNED:= -0.8, 95% CI -1.6, -1.1). CONCLUSIONS/UNASSIGNED:Prenatal PFOA exposure adversely impacted fetal head biometric parameters in participants experiencing higher stress during pregnancy.