Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine.

BACKGROUND: The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. METHODS: Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RESULTS: RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. CONCLUSIONS: Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection.

The prevalence, grouping, and distribution of stressors and their association with anxiety among hospitalized patients.

Anxiety is prevalent among hospital inpatients and it has harmful effects on patient well-being and clinical outcomes. We aimed to characterize the sources of hospital distress and their relationship to anxiety. We conducted a cross-sectional study of inpatients (n = 271) throughout two Southeastern U.S. metropolitan hospitals. Participants completed a survey to identify which of 38 stressors they were experiencing. They also completed the State Trait Anxiety Inventory six-item scale. We evaluated the prevalence of stressors, their distribution, and crude association with anxiety. We then used multivariate logistic regression to estimate the association between stressors and clinically relevant anxiety, with and without adjusting for demographic variables. We used factor analysis to describe the interrelationships among stressors and to examine whether groups of stressors tend to be endorsed together. The following stressors were highly endorsed across all unit types: pain, being unable to sleep, feelings of frustration, being overwhelmed, and fear of the unknown. Stressors relating to isolation/meaninglessness and fear/frustration tend to be endorsed together. Stressors were more frequently endorsed by younger, female, and uninsured or Medicaid-insured patients and being female and uninsured was associated with anxiety in bivariate analysis. After controlling for the sources of distress in multivariate linear analysis, gender and insurance status no longer predicted anxiety. Feelings of isolation, lack of meaning, frustration, fear, or a loss of control were predictive. Study results suggest that multiple stressors are prevalent among hospital inpatients and relatively consistent across hospital unit and disease type. Interventions for anxiety or emotional/spiritual burden may be best targeted to stressors that are frequently endorsed or associated with anxiety, especially among young and female patients.

Randomized, wait-list-controlled pilot study of app-delivered mindfulness for patients reporting chronic pain.

INTRODUCTION: Chronic pain creates economic burden and exerts profound individual and societal harm. Mobile application (app)-delivered mindfulness meditation may be an important approach to self-management of chronic pain. OBJECTIVES: We examined the feasibility, acceptability, and impact of app-delivered mindfulness meditation on pain cognition and daily functioning among patients reporting chronic pain. METHODS: We used a longitudinal, randomized, and wait-list-controlled design (NCT03495726) to evaluate changes in self-reported pain severity, pain catastrophizing, and social and physical functioning among participants randomized to 6 weeks of app-delivered mindfulness meditation, compared with participants randomized to a wait-list control group. RESULTS: Although most participants randomized to the mindfulness group used the app at least once, fewer than half adhered to the instructed program. Participants who did not use the app scored higher on the helplessness component of pain catastrophizing at the start of the study and were less likely to have completed 4 years of college. Participants who reported feeling pressured to enroll in the study were also less likely to adhere to the intervention. Compared with participants randomized to wait-list, those in the mindfulness group reported significant improvements in social functioning, even after controlling for pain severity. Participants randomized to the mindfulness intervention also reported significant improvements in helplessness. App usage was not significantly correlated with changes in social functioning or helplessness scores. CONCLUSIONS: These results suggest that app-delivered mindfulness meditation is beneficial to patients with chronic pain. Identifying characteristics of patients who were adherent highlights important considerations for clinical settings.

Impact of App-Delivered Mindfulness Meditation on Functional Connectivity, Mental Health, and Sleep Disturbances Among Physician Assistant Students: Randomized, Wait-list Controlled Pilot Study.

BACKGROUND: Health care provider and trainee burnout results in substantial national and institutional costs and profound social effects. Identifying effective solutions and interventions to cultivate resilience among health care trainees is critical. Although less is known about the mental health needs of physician assistants (PAs) or PA students, accumulating research indicates that they experience similarly alarming rates of burnout, depression, and emotional exhaustion. Mobile app-delivered mindfulness meditation may be an effective part of salubrious programming to bolster long-term resilience and health among PA students. OBJECTIVE: This study aims to examine the impact of app-delivered mindfulness meditation on self-reported mental health symptoms among PA students. A secondary aim is to investigate changes in brain connectivity to identify neurobiological changes related to changes in mental health symptoms. METHODS: We recruited PA students enrolled in their third semester of PA school and used a longitudinal, randomized, wait-list-controlled design. Participants randomized to the mindfulness group were provided 1-year subscriptions to the 10% Happier app, a consumer-based meditation app, and asked to practice every day for 8 weeks. Before randomization and again after completion of the 8-week program, all participants completed resting-state functional magnetic resonance imaging as well as self-report assessments of burnout, depression, anxiety, and sleep impairment. App use was acquired as a measure of mindfulness practice time. RESULTS: PA students randomized to the mindfulness group reported improvements in sleep impairment compared with those randomized to the wait-list control group (ηp2=0.42; P=.01). Sleep impairment decreased significantly in the mindfulness group (19% reduction; P=.006) but not in the control group (1% reduction; P=.71). There were no other significant changes in mental health for those randomized to app-delivered mindfulness. Across all students, changes in sleep impairment were associated with increased resting-state functional connectivity between the medial prefrontal cortex (a component of the default mode network) and the superior temporal gyrus, as well as between areas important for working memory. Changes in connectivity predicted categorical conversion from impaired to nonimpaired sleep in the mindfulness group. CONCLUSIONS: This pilot study is the first to examine app-based mindfulness for PA students' mental health and investigate the impact of mindfulness on PA students' brain function. These findings suggest that app-delivered mindfulness may be an effective tool to improve sleep dysfunction and that it may be an important part of the programming necessary to reduce the epidemic of suffering among health profession trainees.

The Impact of App-Delivered Mindfulness Meditation on Functional Connectivity and Self-Reported Mindfulness Among Health Profession Trainees.

Objectives: Previous research indicates that mindfulness meditation reduces anxiety and depression and enhances well-being. We examined the impact of app-delivered mindfulness meditation on resting state functional MRI (fMRI) connectivity among physician assistant (PA) students and surgery residents. Methods: PA students and residents were randomized to receive a popular meditation app or to wait-list control group. Before and after the 8-week meditation period, we acquired fMRI scans of participants' resting state, and participants completed a self-report measure of mindfulness. We used a 2 × 2, within- and between-group factorial design and leveraged a whole-brain connectome approach to examine changes in within- and between-network connectivity across the entire brain, and to examine whether changes in connectivity were associated with app use or to changes in self-reported mindfulness. Results: Meditation practitioners exhibited significantly stronger connectivity between the frontoparietal network and the left and right nucleus accumbens and between the default mode (DMN) and salience networks, among other regions. Mindfulness practice time was correlated with increased connectivity between the lateral parietal cortex and the supramarginal gyrus, which were also positively correlated with increased scores on the "Describing" subscale of the Five Facet Mindfulness Questionnaire between baseline and post-meditation. These findings are consistent with previous research indicating that mindfulness-based interventions alter functional connectivity within the DMN and between the DMN and other networks both during meditation and at rest, as well as increased connectivity in systems important for emotion and reward. Conclusions: Recent commentaries call for healthcare provider and trainee wellness programs that are sustainable and preventive in nature rather than reactive; these data indicate that even brief sessions of app-delivered mindfulness practice are associated with functional connectivity changes in a dose-dependent manner.

Compassion Meditation Training for Hospital Chaplain Residents: A Pilot Study.

This study examines the effectiveness of incorporating compassion meditation training into a clinical pastoral education (CPE) curriculum to enhance compassion satisfaction and reduce burnout among hospital chaplain residents. Specifically, a longitudinal, quasi-experimental design was used to examine the impact of Cognitively-Based Compassion Training (CBCT), a group-delivered compassion meditation intervention. Hospital chaplain residents (n = 15) were assigned to participate in a CBCT intervention or a waitlist comparison group. Chaplains assigned to CBCT reported significant decreases in burnout and anxiety compared to the waitlist group; effects were not maintained at 4-month follow-up. Other outcomes, including compassion satisfaction, did not differ significantly but were trending in the expected direction. Findings suggest that compassion meditation training incorporated into CPE promotes chaplain wellbeing, although it may be necessary to extend CBCT throughout residency to sustain effects.