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Item A Preliminary Study of Short-Term Sexual Function and Satisfaction among Men Post-Myocardial Infarction(Sage, 2022) Smith, Asa B.; Barton, Debra L.; Davis, Matthew; Jackson, Elizabeth A.; Smith, Jacqui; Wittmann, Daniela; School of NursingSexuality is an important component of holistic quality of life, and myocardial infarction (MI) negatively influences many aspects of sexuality, including sexual function. However, there is limited literature that examines sexuality beyond the most basic physical components. This pilot study aimed to describe the relationships between the physical, psychologic, and social domains of holistic sexuality at an early timepoint post-MI. Adult men post-MI were mailed self-report surveys at two weeks post discharge. Physical domains of sexuality were measured with the arousal, orgasm, erection, lubrication, and pain subscales of the Male Sexual Function Index, (MSFI). The social domain utilized the sexual satisfaction subscale of the MSFI. The psychologic domain included the desire subscale of the MSFI and sexual fear (Multidimensional Sexuality Questionnaire (MSQ)). Spearman correlations were estimated to examine associations among the different measurement subscales. Twenty-four men post-MI were analyzed. Average scores on the MSFI were 9.2 (SD 7.7). Desire and satisfaction were the highest scoring subscales among men when compared with other subscales (i.e., erection, lubrication). There was minimal evidence supporting a relationship between sexual fear and function. Additional research is also needed with larger samples, and among women post-MI.Item Acceptance and commitment therapy for breast cancer survivors with fear of cancer recurrence: A 3-arm pilot randomized controlled trial(Wiley, 2020) Johns, Shelley A.; Stutz, Patrick V.; Talib, Tasneem; Cohee, Andrea A.; Beck-Coon, Kathleen A.; Brown, Linda F.; Wilhelm, Laura R.; Monaham, Patrick O.; LaPradd, Michelle L.; Champion, Victoria L.; Miller, Kathy D.; Giesler, R. BrianBackground Fear of cancer recurrence (FCR) has a profound negative impact on quality of life (QOL) for many cancer survivors. Breast cancer survivors (BCS) are particularly vulnerable, with up to 70% reporting clinically significant FCR. To the authors' knowledge, evidence-based interventions for managing FCR are limited. Acceptance and commitment therapy (ACT) promotes psychological flexibility in managing life's stressors. The current study examined the feasibility and preliminary efficacy of group-based ACT for FCR in BCS. Methods Post-treatment BCS (91 patients with stage I-III disease) with clinical FCR randomly were assigned to ACT (6 weekly 2-hour group sessions), survivorship education (SE; 6 weekly 2-hour group sessions), or enhanced usual care (EUC; one 30-minute group coaching session with survivorship readings). FCR severity (primary outcome) and avoidant coping, anxiety, post-traumatic stress, depression, QOL, and other FCR-related variables (secondary outcomes) were assessed at baseline (T1), after the intervention (T2), 1 month after the intervention (T3), and 6 months after the intervention (T4) using intent-to-treat analysis. Results Satisfactory recruitment (43.8%) and retention (94.5%) rates demonstrated feasibility. Although each arm demonstrated within-group reductions in FCR severity over time, only ACT produced significant reductions at each time point compared with baseline, with between-group differences at T4 substantially favoring ACT over SE (Cohen d for effect sizes, 0.80; P < .001) and EUC (Cohen d, 0.61; P < .01). For 10 of 12 secondary outcomes, only ACT produced significant within-group reductions across all time points. By T4, significant moderate to large between-group comparisons favored ACT over SE and EUC with regard to avoidant coping, anxiety, depression, QOL, and FCR-related psychological distress. Conclusions Group-based ACT is a feasible and promising treatment for FCR and associated outcomes in BCS that warrants testing in larger, fully powered trials.Item Communication at diagnosis of venous thromboembolism: Lasting impact of verbal and nonverbal provider communication on patients(Elsevier, 2022-01-15) Hernandez-Nino, Jackeline; Thomas, Mary; Alexander, Andreia B.; Ott, Mary A.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground: Establishing trust and effective communication can be challenging in the emergency department, where a prior relationship between patient and provider is lacking and decisions have to be made rapidly. Venous thromboembolism (VTE) represents an emergent condition that requires immediate decision making. Objective: The aim of this paper was to document the experiences, perceptions, and the overall impact of health care provider communication on patients during the diagnosis of VTE in the emergency department. Methods: This was a qualitative method study using semistructured interviews to increase understanding of the patient experience during the diagnosis of VTE and impact of the health care provider communication on subsequent patient perceptions. Results: A total of 24 interviews were conducted. Content analysis revealed that certain aspects of health care providers' communication-namely, word choice, incomplete information, imbalance between fear over reassurance and nonverbal behavior-used to deliver and explain VTE diagnosis, treatment, and prognosis increases patients' fears. Conclusion: These interviews elucidate areas for improvement of communication in the emergency care setting for acute VTE.Item Dissecting the Functional Heterogeneity of Serotonergic Systems That Regulate Fear and Panic(2019-10) Setubal Bernabe, Cristian; Cummins, Theodore R.; Engelman, Eric; Johnson, Philip L.; Truitt, William A.Serotonin (5-HT) is heavily implicated in severe anxiety and trauma-related disor-ders, such as panic and post-traumatic stress disorders. Overall, site-specific pharmacolog-ical manipulations show that while 5-HT enhances anxiety-associated/avoidance behaviors in the amygdala, 5-HT inhibits panic-associated escape behaviors in the perifornical hypo-thalamus region (PeFR). Yet, our understanding of how specific serotonergic networks and co-transmitters regulate these conditions, but also other aspects of innate panic (e.g., car-dioexcitation or thermal response that occur during a flight or escape response) or condi-tioned fear behaviors is still elusive. Therefore, utilizing circuit-based gain- and loss-of-function approaches to selectively manipulate amygdala- and PeFR-projecting sero-tonergic systems, we hypothesize that specific serotonergic networks projecting to the amygdala and PeFR respectively enhance conditioned fear responses and attenuate innate panic-associated behaviors and physiological responses. There are two main chapters in this dissertation. In Chapter III, retrograde tracing revealed that the amygdala-projecting neurons from dorsal Raphe (DR) were almost exclusively serotonergic (92-95%) concen-trated in the dorsal/ventral (DRD/DRV) DR, with few non-serotonergic neurons. While selective lesioning of this network with saporin toxin (SAP) facilitated the extinction of conditioned fear behavior, selective optogenetic activation of amygdala-projecting DRD/DRV cell bodies using intersectional genetics reduced extinction of conditioned fear behavior and enhanced anxiety avoidance. In Chapter IV, retrograde tracing showed that the PeFR was innervated by equally selective serotonergic networks concentrated in the lateral wings DR (lwDR) and median Raphe (MR). Contrasting with the results from the amygdala-innervating 5-HT system, lesioning the PeFR-projecting serotonergic network from lwDR/MR was accompanied by reduced extinction of conditioned fear behavior, in-creased anxiety avoidance, and increased CO2-induced panic (elevated escape responses and enhanced cardioexcitation). Conversely, selective activation of lwDR/MR serotonergic terminals in the PeFR decreased anxiety-associated behaviors; inhibited CO2-induced panic, and induced unconditioned and conditioned place preferences. The circuit-based ap-proach data presented here show that amygdala- and PeFR-projecting 5-HT neurons com-prise distinct circuits underlying opposite roles enhancing anxiety/fear responses in the amygdala and dampening fear/panic responses in the PeFR. The identification of distinct circuits controlling anxiety, fear, and panic responses is a fundamental step towards the development of more effective therapies for psychiatric conditions such as anxiety and trauma-related disorders.Item Effect of a School-Based Educational Intervention About the Human Papillomavirus Vaccine on Psychosocial Outcomes Among Adolescents: Analysis of Secondary Outcomes of a Cluster Randomized Trial(American Medical Association, 2021-11-01) Davies, Cristyn; Marshall, Helen S.; Zimet, Gregory; McCaffery, Kirsten; Brotherton, Julia M.L.; Kang, Melissa; Garland, Suzanne; Kaldor, John; McGeechan, Kevin; Skinner, S. Rachel; Pediatrics, School of MedicineImportance: Delivery of vaccination to adolescents via a school-based program provides an opportunity to promote their involvement in health decision-making, service provision, and self-efficacy (belief in one's ability to perform a certain behavior). Objective: To examine the effect of a human papillomavirus (HPV) vaccination education and logistical intervention on adolescent psychosocial outcomes. Design, setting, and participants: In this cluster randomized trial and process and qualitative evaluation, adolescents aged 12 to 13 years (first year of high school) were recruited at high schools in Western Australia (WA) and South Australia (SA) in 2013 and 2014. Statistical analysis was performed from January 2016 to December 2020. Interventions: The complex intervention consisted of an adolescent intervention to promote knowledge and psychosocial outcomes, shared decisional support tool, and logistical strategies. Main outcomes and measures: Prespecified secondary outcomes were assessed. The HPV Adolescent Vaccination Intervention Questionnaire (HAVIQ) was used to measure changes in adolescent knowledge (6-item subscale), fear and anxiety (6-item subscale), self-efficacy (5-item subscale), and decision-making (8-item subscale). The hypothesis was that the intervention would improve adolescent involvement in vaccine decision-making (measured before dose 1 only), improve vaccine-related self-efficacy, and reduce vaccine-related fear and anxiety (measured before doses 1, 2, and 3). Mean (SD) scores for each subscale were compared between intervention and control students. In the process evaluation, focus groups were conducted. Analyses of the HAVIQ data were conducted from 2016 to 2020. Qualitative analyses of the focus groups were undertaken from 2017 to 2020. Results: The trial included 40 schools (21 intervention and 19 control) across sectors with 6967 adolescents (mean [SD] age, 13.70 [0.45] years). There were 3805 students (1689 girls and 2116 boys) in the intervention group and 3162 students (1471 girls and 1691 boys) in the control group. The overall response rate for the HAVIQ was 55%. In WA, where parental consent was required, the response rate was 35% (1676 of 4751 students); in SA, where parental consent was not required, it was 97% (2166 of 2216 students). The mean (SD) score for decision-making in the intervention group before dose 1 was 3.50 (0.42) of 5 points and 3.40 (0.40) in the control group, a small but significant difference of 0.11 point (95% CI, 0.06 to 0.16 point; P < .001). There was a small difference in favor of the intervention group in reduced vaccination-related anxiety (pre-dose 1 difference, -0.11 point [95% CI, -0.19 to -0.02 point]; pre-dose 2 difference, -0.18 point [95% CI, -0.26 to -0.10 point]; pre-dose 3 difference, -0.18 [95% CI, -0.24 to -0.11]) and increased vaccination self-efficacy (pre-dose 1 difference, 4.0 points; [95% CI, 1.0 to 7.0 points]; pre-dose 2 difference, 4.0 points [95% CI, 2.0 to 6.0 points]; pre-dose 3 difference, 3.0 points [95% CI, 1.0 to 5.0 points]). Focus group data from 111 adolescents in 6 intervention and 5 control schools revealed more confidence and less anxiety with each vaccine dose. Conclusions and relevance: In this cluster randomized trial, there was a small difference in adolescent decisional involvement and vaccine-related confidence and reduced vaccination-related fear and anxiety that was maintained throughout the vaccine course in the intervention vs control groups. Guidelines for vaccination at school should incorporate advice regarding how this outcome can be achieved.Item Fear of Breast Cancer Recurrence in African-American and Caucasian Breast Cancer Survivors(Office of the Vice Chancellor for Research, 2010-04-09) Ziner, Kim Wagler; Russell, Kathleen; Champion, Victoria; Miller, Kathy D.Problem. Fear of breast cancer recurrence is a concern for 55-90% of long-term breast cancer survivors. Background. Fear of recurrence is recognized as a prevalent and long-term psychosocial consequence of surviving cancer. Breast cancer survivors often identify more than one worry about what a recurrence might threaten in their health, work, and family function (Vickberg, 2001, 2003; Ziner, 2008). Although more research has been conducted with Caucasian breast cancer survivors, less is known about the nature of fear of recurrence worries in African American breast cancer survivors. Purpose. The purpose of this study was to compare fear of recurrence and worries related to thoughts of recurrence between African-American (AA-BCS) and Caucasian breast cancer survivors ( C-BCS). Theory. Emotion theorist, such as Lazarus (1991) suggest that fear is an emotional response to an identifiable object, thought or event that is perceived as harmful. Methods. This is a secondary analysis of a larger study comparing quality of life of AA-BCS and C-BCS using a cross-section survey design. Sample. Female breast cancer survivors ( AA-BCS N = 62, C-BCS N = 72) who were 2-10 years post treatment. Measures. Concerns about Recurrence Sale (CARS) Vickberg (2003) is a scale with 30 Likerttype items and 5 sub-scales: Fear of recurrence Index (overall fear frequency, intensity and consistency). Four (4) subscales of what BCS worry about: Health worries, Role worries, Womanhood worries, and Death worries. Validity. Content analysis of focus group data (N=21) AA-BCS showed that no changes were recommended in the CARS. (Russell, Personal communication) Reliability. The CARS and subscales were found to have Good to adequate Cronbach’s alpha’ for AA-BCS and C-BCS. Specifically, FRI = .92 AA-BCS, .90 C-BCS, Health worries = .93 AA-BCS, .92 C-BCS, Role worries = .75 AA-BCS, .87 C-BCS, Womanhood worries .89, AABCS, .90, C-BCS, Death worries .81 AA-BCS, .92 C-BCS. Analysis. ANCOVA was used for analysis controlling for age, time since diagnosis, income, marital status, years of education and body mass index. Results. Fear of recurrence Indexes between AA-BCS (mean 9.8) and C-BCS (mean 11.5) were not statistically different (p = .199). Health worries (AA- BCS mean 1.1, C-BCS mean 1.6, p= .018), Role worries (AA-BCS mean .8, C- BCS mean 1.2, p = .05), and Death worries (AA- BCS mean 1.3,C- BCS mean 2.2, p = .01) were significantly different between AA-BCS and C-BCS. Womanhood worries were not significantly different. Conclusions. AA-BCS and C-BCS were equally afraid of a recurrence. Except of womanhood worries, AA-BCS had lower mean health, role and death worries than C-BCS. Implications. Understanding the underlying worries related to overall fear of recurrence can lead to more focused and perhaps effective nursing intervention for AA-BCS and C-BCS.Item Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms(Society for Neuroscience, 2022) Tanriverdi, Büşra; Gregory, David F.; Olino, Thomas M.; Ely, Timothy D.; Harnett, Nathaniel G.; van Rooij, Sanne J. H.; Lebois, Lauren A. M.; Seligowski, Antonia V.; Jovanovic, Tanja; Ressler, Kerry J.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; McGrath, Meghan E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Pearson, Claire; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sanchez, Leon D.; Bruce, Steven E.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Smoller, Jordan W.; Harte, Steven E.; Elliott, James M.; McLean, Samuel A.; Kessler, Ronald C.; Koenen, Karestan C.; Stevens, Jennifer S.; Murty, Vishnu P.; Emergency Medicine, School of MedicineHippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal. Significance Statement: Alterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.Item Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses(Springer Nature, 2024-01-25) Bernabe, Cristian S.; Caliman, Izabela F.; de Abreu, Aline R. R.; Molosh, Andrei I.; Truitt, William A.; Shekhar, Anantha; Johnson, Philip L.; Anatomy, Cell Biology and Physiology, School of MedicineThe serotonin (5-HT) system is heavily implicated in the regulation of anxiety and trauma-related disorders such as panic disorder and post-traumatic stress disorder, respectively. However, the neural mechanisms of how serotonergic neurotransmission regulates innate panic and fear brain networks are poorly understood. Our earlier studies have identified that orexin (OX)/glutamate neurons within the perifornical hypothalamic area (PFA) play a critical role in adaptive and pathological panic and fear. While site-specific and electrophysiological studies have shown that intracranial injection and bath application of 5-HT inhibits PFA neurons via 5-HT1a receptors, they largely ignore circuit-specific neurotransmission and its physiological properties that occur in vivo. Here, we investigate the role of raphe nuclei 5-HT inputs into the PFA in panic and fear behaviors. We initially confirmed that photostimulation of glutamatergic neurons in the PFA of rats produces robust cardioexcitation and flight/aversive behaviors resembling panic-like responses. Using the retrograde tracer cholera toxin B, we determined that the PFA receives discrete innervation of serotonergic neurons clustered in the lateral wings of the dorsal (lwDRN) and in the median (MRN) raphe nuclei. Selective lesions of these serotonergic projections with saporin toxin resulted in similar panic-like responses during the suffocation-related CO2 challenge and increased freezing to fear-conditioning paradigm. Conversely, selective stimulation of serotonergic fibers in the PFA attenuated both flight/escape behaviors and cardioexcitation responses elicited by the CO2 challenge and induced conditioned place preference. The data here support the hypothesis that PFA projecting 5-HT neurons in the lwDRN/MRN represents a panic/fear-off circuit and may also play a role in reward behavior.Item Interaction of stress and alcohol on discriminating fear from safety and reward in male and female rats(Springer Nature, 2023) Hackleman, Abigail; Ibrahim, Muhja; Shim, Kevin; Sangha, Susan; Psychiatry, School of MedicineRationale: Stressful events can have lasting and impactful effects on behavior, especially in terms of appropriate fear regulation and reward seeking. Our prior work in rats has shown baseline sex differences in fear expression and sucrose seeking in a discriminative reward-fear-safety conditioning task. Objectives: The objectives of the current study were to determine how prior stress may affect alcohol consumption across a reward-fear-safety learning task, and how prior alcohol history may interact with stress to impact learning in this task. Methods: Male and female Long Evans rats were given home cage intermittent 24 h access to both water and alcohol for 5 weeks. A subset of rats then received exposure to stress (15 unsignaled footshocks), while remaining unstressed rats received context exposure without shock. One week later, all rats were trained on the same reward-fear-safety cue task while having continuous home cage access to both water and alcohol. Results: All rats increased consumption (g/kg/24 h) across the 5 weeks of intermittent access, with females showing higher consumption levels. Stress exposure did not alter alcohol consumption in the week following stress, but did increase home cage alcohol consumption during later reward-fear-safety cue learning. Stress in both sexes also elevated freezing levels to the reward cue resulting in decreased sucrose seeking and was positively correlated with home cage alcohol consumption. Conclusions: While stress increased drinking in both males and females, the effects of stress were particularly pronounced in females, indicating our results could be capturing a higher propensity for females to display stress-induced drinking.Item Patient-Reported Testing Burden of Breast Magnetic Resonance Imaging Among Women With Ductal Carcinoma In Situ: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112)(American Medical Association, 2021-11-01) Fazeli, Soudabeh; Snyder, Bradley S.; Gareen, Ilana F.; Lehman, Constance D.; Khan, Seema A.; Romanoff, Justin; Gatsonis, Constantine A.; Miller, Kathy D.; Sparano, Joseph A.; Comstock, Christopher E.; Wagner, Lynne I.; Carlos, Ruth C.; Surgery, School of MedicineImportance: The use of magnetic resonance imaging (MRI) in pretreatment planning of ductal carcinoma in situ (DCIS) remains controversial. Understanding changes in short-term health-related quality of life associated with breast MRI would allow for a more complete comparative effectiveness assessment. Objective: To assess whether there are changes in patient-reported quality of life associated with breast MRI among women diagnosed with DCIS. Design, setting, and participants: This cohort study was a substudy of a nonrandomized clinical trial conducted at 75 participating US institutions from March 2015 to April 2016. Women recently diagnosed with unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. A total of 355 women met the eligibility criteria and underwent the study MRI. Data analysis was performed from June 3, 2020, to July 1, 2021. Exposures: Participants underwent bilateral breast MRI within 30 days of study registration and before surgery. Information on patient-reported testing burden for breast MRI was collected after MRI and before surgery. Main outcomes and measures: The primary outcome of this substudy was the patient-reported testing burden of breast MRI, measured by the Testing Morbidities Index (TMI) summated scale score. The TMI is a 7-item instrument that evaluates the temporary changes in quality of life associated with imaging before, during, and after the test (0 represents the worst possible, 100 the hypothetical ideal test experience). Results: Of the 355 women who met the eligibility criteria, 244 (69%) completed both questionnaires and were included in this analysis. The median age was 59 years (range, 34-85 years). The mean MRI TMI summated scale score was 85.9 (95% CI, 84.6-87.3). Of the 244 women, 142 (58%) experienced at least some fear and anxiety before the examination, and 120 women (49%) experienced fear and anxiety during the examination. A total of 156 women (64%) experienced pain or discomfort during the examination. In multivariable analyses, greater test-related burden was associated with higher levels of cancer worry (regression coefficient, -2.75; SE, 0.94; P = .004). Conclusions and relevance: In this cohort study, a clinically meaningful breast MRI testing burden among women with DCIS was revealed that was significantly associated with cancer worry. Understanding the potential quality-of-life reduction associated with MRI, especially when used in combination with mammography, may allow development of targeted interventions to improve the patient experience.