VA Boston Healthcare System

Chronic insomnia causes malaise and is associated with depression, irritability, cognitive impairment, impaired alertness, and substance abuse. Individuals with posttraumatic stress disorder (PTSD) often have both inadequate and fragmented sleep, putting them at elevated risk for these consequences. Sleep abnormalities in patients with PTSD include frequent trauma-related nightmares, prolonged sleep latency, frequent interruptions, early awakening, nighttime behavioral disorders, and disruptions of sleep cycles. Here, we review the pharmacological treatment for nightmares with an emphasis on noradrenergic (NA) signaling, following the clinical observation that medication treatment with alpha-1 adrenergic blocking agents, such as prazosin, improves nightmares. We discuss the randomized controlled trials (RCTs) examining prazosin's impact on nightmares, including its efficacy and safety, and the limitations of the studies. In addition, we review the accumulating evidence from case reports, chart review, and small studies for several other anti-alpha-1 agents (specifically doxazosin, terazosin, and tamsulosin) and their efficacy in treating nightmares in PTSD. RCT studies for prazosin suggest clinical efficacy for PTSD-related nightmare disorder in subpopulations of individuals with this condition. Case studies, pilot, and open label trails suggest possible clinical use of terazosin, tamsulosin, and doxazosin in PTSD-related nightmares, however, further RCTs are needed. When available and clinically tolerated, prazosin continues to have the best evidence base for use in PTSD-related nightmares. When prazosin use is not feasible, alternative alpha-1 blockers may be effective in a subset of patients.

Building on the identification of ABCB5 as a marker of limbal stem cells (LSCs), this study examines CD63, a newly identified molecule co-expressed with ABCB5 in limbal epithelial cells, to define its role in maintaining corneal epithelial cell identity. RNA sequencing (RNA-seq) was performed on flow cytometry-sorted Abcb5-positive and Abcb5-negative murine corneal epithelial cells. CD63 expression in human corneal tissue was assessed by immunostaining. CD63 was silenced in cultured human limbal epithelial cells using siRNA-mediated knockdown and resulting molecular and cellular changes were analyzed by qRT-PCR, flow cytometry, RNA-seq, Western blotting, and cell proliferation assays. RNA-seq analysis revealed increased expression of LSC markers, including Krt15, Krt6b, Fgfr1, Gpha2, Ifitm3, Ifitm1, and Cd63, and decreased expression of differentiation-associated markers, such as Krt12, Gja1, and Ovol1 in Abcb5-positive cells. Immunostaining of human corneal tissue demonstrated strong CD63 expression localized to the limbal region. Knockdown of CD63 in cultured human limbal epithelial cells resulted in reduced cell proliferation and significantly decreased expression of corneal epithelium-enriched genes, including KRT12, CLU, ALDH1A1, ALDH3A1, TGFBI, and MYEOV. Notably, CD63 knockdown led to an approximately 50% reduction in expression of PAX6, a key transcriptional regulator of corneal epithelial identity. CD63 is highly expressed in the human limbus and is required for maintaining cell proliferation and the expression of corneal epithelium-specific proteins, likely through regulation of PAX6. These findings establish CD63 as a functionally important component of limbal stem cell biology and a key contributor to corneal epithelial homeostasis.

The behavioural tendency to expand sleep opportunity to compensate for prior sleep loss is referred to as 'sleep extension.' It is believed that sleep extension (here referred to as 'sleep opportunity extension' [SOE]) is the primary perpetuating factor explaining the transition from acute to chronic insomnia. Recently, this proposition was prospectively evaluated by assessing how sleep opportunity varied, week-by-week, relative to the incidence of acute and chronic insomnia. Significant differences in sleep opportunity before and after onset of acute insomnia were not detected. In the present analysis, a more granular evaluation was undertaken to assess whether SOE occurs on the nights and/or weekends following poor sleep. The data set (n = 1243) was modelled by group (good sleepers and participants with acute insomnia) for SOE occurring on the nights and weekends following poor nights of sleep (i.e., ≥ 30 min of sleep latency and/or nocturnal wakefulness and/or early morning awakenings) for the post-acute insomnia interval. A linear mixed effects model was used to account for up to one year of night-to-night sleep per participant. During the weekdays, sleep opportunity following a poor night of sleep was not found to increase (overall or by group) (< 5 min). During the weekends, all groups tended to decrease their sleep opportunity. This counterintuitive finding casts further doubt on the proposition that SOE is responsible for the transition between acute insomnia and chronic insomnia. This finding does not, however, change the relevance of addressing the mismatch between sleep opportunity and ability as part of behavioural treatment.

The Veterans Health Administration is promoting patient-reported outcome measure (PROM) collection for measurement-based mental health care. Understanding veteran preferences about how and when to complete PROMs is critical to support their implementation. We examined veteran preferences for timing and use of different technology platforms to complete mental health-related PROMs. We invited a national sample of 1373 veterans to complete a survey; 858 (62.5%) responded. Surveys asked about veteran preferences for how and when to complete mental health-related PROMs. We characterized responses using descriptive statistics and estimated multiple logistic regression models to examine associations between veteran demographic and health characteristics and preferences for completing PROMs. Most veterans preferred completing PROMs between appointments (607/801, 75.8%) using features of a patient portal (410/801, 51.2%), during appointments (589/801, 73.5%) verbally (413/801, 51.6%), and while at the medical center (480/801, 59.9%) on paper (189/801, 23.6%) or a tablet computer (180/801, 22.5%). Hispanic (vs non-Hispanic) veterans had 3.32 (95% CI 1.04-10.58) times higher odds of preferring to complete PROMs at the medical center, and veterans with lower (vs higher) socioeconomic status had lower odds (odds ratio 0.61, 95% CI 0.40-0.93) of preferring to complete PROMs in between appointments but 1.97 (95% CI 1.23-3.16) times higher odds of preferring to complete PROMs during appointments. As the Veterans Health Administration and other health care systems seek to expand the integration of PROM data into health care services, adaptive and flexible approaches to PROM administration that align with patient preferences, including those that leverage technology platforms in the remote collection of these data, may bolster implementation. Our results indicate that such implementation efforts should consider patient ethnicity and socioeconomic status. Our findings further suggest that these efforts could benefit from incorporating PROM administration into online patient portals, developing mobile health apps that support PROM completion through patients' personal devices in between clinical encounters, and engaging care team members in PROM administration during appointments.

In 2022, over 6 million individuals in the United States were affected by opioid use disorder (OUD), and more than 81,000 died from opioid-related overdoses. This umbrella review synthesized evidence on the associations between a broad range of social determinants of health (SDoH) and OUD/overdose. An umbrella review of meta-analyses and reviews on SDoH and OUD/overdose was conducted using PubMED, PsycINFO, Embase, and Web of Science. A total of 29 reviews were deemed appropriate for inclusion. Adverse childhood experiences and unemployment were associated with OUD outcomes. In the United States, immigrant status was associated with a lower risk of OUD, though this risk increased in subsequent generations. Individuals who experienced intimate partner violence and sexual minority individuals showed high prevalence of OUD. For overdose, associations were found in unemployment, low income, high poverty, and justice system involvement. Significant increases in odds of overdose were noted among individuals experiencing homelessness, lacking private insurance, engaging in sex work for pay, or witnessing an overdose. This study identified SDoH associated with OUD outcomes and overdose risk, with findings having implications from a public health perspective for clinical practice, public health policy, and research priorities. There is a need for meta-analyses to clarify the magnitude of SDoH influences on OUD/overdose, with the goal of informing targeted interventions to reduce opioid-related morbidity and mortality. The most comprehensive umbrella review to date on intersections among SDoH, OUD outcomes, and overdose risk.