Parameterizing Toxic Stress in Early Childhood: Maternal Depression, Maltreatment, and HPA-Axis Variation in a Pilot Intervention Study.

Adverse experiences superseding a child's capacity to sustain regulation of emotion and adaptive function are theorized to constitute "toxic stressors" when they induce a deleterious biological response within an individual. We ascertained presumptive parameters of toxic stress among 164 low-income infants and toddlers (ages 4-48 months) from 132 families enrolled in Early Head Start (EHS). We randomized a subset of these families into a pilot intervention arm of parenting education (the Incredible Years, TIY), which supplemented the EHS curriculum. Official report child abuse and neglect (CAN) and child behavior were serially ascertained over the course of the study. We observed relatively low associations among maternal depression, CAN, caregiver-child relationship quality, hair cortisol, and adverse child behavioral outcomes. Moreover, despite poverty and the high prevalence (51%) of CAN in this sample, the frequency of clinical-level internalizing and externalizing behavior among the children did not exceed that of the general population, by their parents' report. The pilot supplementation of EHS with TIY improved attendance in group meetings but did not significantly reduce adverse behavioral outcomes or CAN. This study revealed marked independence of standard indices of toxic stress (child maltreatment, maternal depression, caregiver emotional unavailability) which have been presumed to be risk factors for the development of psychopathology. That they were weakly inter-correlated, and only modestly predictive of child behavioral outcomes in this EHS sample, caution against presumptions about the toxicity of individual stressors, highlight the importance of ascertaining risk (and compensatory influences) comprehensively, suggest buffering effects of programs like EHS, and demonstrate the need for greater understanding of what parameterizes resilience in early childhood.

More often than not, we're in sync: patient and caregiver well-being over time in stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an aggressive medical procedure which significantly impacts the shared emotional well-being of patients and family caregivers (FC). Prior work has highlighted the significant overlap in well-being among patients and FCs; however, how this interdependence may change over the course of HSCT has received less attention. METHODS: We conducted secondary analyses of a supportive intervention delivered to 154 FCs of HSCT patients and examined relationships at baseline, 6 weeks, 3 and 6 months post-HSCT. Actor Partner Interdependence Modeling examined patient quality of life (QOL) and FC anxiety/depression. RESULTS: The data did not fit a multigroup approach limiting our ability to test intervention effects; however, bivariate analyses indicated FC depression significantly correlated to patient QOL at baseline (r = - .32), 6 weeks (r = - .22) and 6 months post-HSCT (r = - .34; p's < .05); whereas FC anxiety was only correlated with patient QOL at the first two timepoints (p's < .05). There was an unexpected, partner effect such that worse patient QOL at 6-weeks significantly related to lower FC depression at 3-months (B = .193; p = .026) and changed direction with patient QOL at 3-months being related to more FC depression at 6-months (B = - .187; p = .001). CONCLUSIONS: These findings highlight the significant, yet nuanced, interdependence of patient QOL and FC well-being during HSCT. Specifically, greater interdependence was observed between patient QOL and FC depression compared to FC anxiety, suggesting potential treatment targets for patients and their families. Trial was registered at ClinicalTrials.gov Identifier: NCT02037568; first registered: January 16, 2014; https://clinicaltrials.gov/ct2/show/NCT02037568.

Association between employment status change and depression and anxiety in allogeneic stem cell transplant caregivers.

PURPOSE: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a demanding treatment that requires caregiver support during the first 100 days post-transplant. Little is known about the association between caregivers' employment changes and their well-being during this lengthy and challenging time when caregivers may be balancing work with caregiving responsibilities. METHODS: We used data from employed caregivers of Allo-HSCT patients who participated in two randomized clinical trials (N = 187) of an intervention for caregivers. Caregiver depression and anxiety were assessed using the Center for Epidemiologic Studies Depression and the Spielberger State-Trait Anxiety Inventory. ANCOVA was used to measure the associations between reducing work with depression and anxiety. Caregiver's demographics and baseline employment status were controlled in the analysis along with the patient's transplant conditioning intensity. RESULTS: Approximately 45% of caregivers reduced hours worked following the resumption of their caregiving duties. These caregivers, on average, had 3.49 points higher depression scores than caregivers who did not report a reduction in work (p < 0.01). Similarly, these caregivers also reported, on average, 3.56 higher anxiety scores (p < 0.10). CONCLUSIONS: Caregivers who reduced hours worked while caregiving reported greater distress. The underlying cause of this distress deserves further investigation. IMPLICATIONS FOR CANCER SURVIVORS: Caregivers of patients diagnosed with cancer may experience considerable stress related to work discontinuation and caregiving. Interventions are needed to support caregivers who are trying to balance work and caregiving responsibilities.

Discrimination and Sleep Impairment in American Indians and Alaska Natives.

BACKGROUND: Sleep impairment may be a key pathway through which discrimination undermines health. Links between discrimination and sleep in American Indians and Alaska Natives (AI/AN) have not been established. Further, it is unclear if such links might depend on the timing of discrimination or if socioeconomic status (SES) might buffer the impact of discrimination. PURPOSE: To investigate associations between interpersonal discrimination and sleep impairment in urban AI/AN, for both lifetime and recent discrimination, and controlling for other life stressors. Education and income, indices of SES, were tested as potential moderators. METHODS: A community sample of urban AI/AN (N = 303, 18-78 years old, 63% female) completed self-report measures of sleep impairment, lifetime and recent discrimination, depressive symptoms, perceived stress, other life stressors (childhood adversity and past year major events), and socio-demographic characteristics. RESULTS: Lifetime discrimination was associated with impaired sleep in AI/AN after adjustment for socio-demographic characteristics, recent depressive symptoms, perceived stress, and other life stressors. Past-week discrimination was associated with sleep in unadjusted but not adjusted models. Education, but not income, was found to buffer the effects of both lifetime and past-week discrimination on sleep in adjusted models. CONCLUSION: Lifetime discrimination uniquely accounts for sleep impairment and may be especially harmful in those with less education. These findings suggest targeting interventions to those most in need. Limitations include the cross-sectional nature of the data. Longitudinal and qualitative work is needed to understand how education may buffer the effects of discrimination on sleep and perhaps other health problems in AI/AN.

Emotional Availability as a Moderator of Stress for Young Children and Parents in Two Diverse Early Head Start Samples.

Positive parent-child relationship quality is critical for buffering children from the effects of stress on development. It is thus vital to develop interventions that target parent-child relationship quality for families experiencing stress. We examined the moderating role of parent-child relationship quality (as measured by parental emotional availability [EA]) in the intergenerational association between parental adverse childhood experiences (ACEs) and their young children's hair cortisol concentrations (HCCs)-a physiological marker of cumulative hypothalamic pituitary adrenal (HPA)-axis activity. Using data from 127 parent-child dyads collected by two of six ACF-funded Buffering Toxic Stress consortium sites, we tested interaction effects of parental ACEs with parental EA on young children's (Mage = 18.38, SDage = 7.10) HCC. Results revealed curvilinear main effects such that higher parental ACEs were significantly associated with greater HCC and stronger associations occurred at higher levels of parental ACEs. However, this association was moderated by parental EA. Thus, among children with higher parental history of ACEs, children of parents with higher EA had lower HCC compared to children of parents with lower EA. These findings provide support for the risk-buffering and risk-exacerbating role of parent-child relationship quality (e.g., EA) for the transmission of parents' early life adversity on their children's HPA-axis activity, documented here in a racially and ethnically diverse sample of children and parents served by Early Head Start. Findings suggest that intervention and prevention efforts targeting stress response in children of mothers with childhood adversity should also support parents in building an emotionally available relationship with their children.

Older and Wiser? Age Moderates the Association Between Discrimination and Depressive Symptoms in American Indians and Alaska Natives.

Objectives: To examine age differences in the association between discrimination and depressive symptoms among urban American Indians and Alaska Natives (AI/AN). Methods: A sample of 303 urban AI/AN (18-78 years old) reported on lifetime and past-week experiences of racial discrimination and depressive symptoms. Depressive symptoms were regressed on racial discrimination, age, and their interaction, adjusting for demographic factors and other life stressors. Results: Lifetime and past-week discrimination were significantly associated with depressive symptoms, and these associations were stronger among younger than older adult AI/AN. Discussion: The results are consistent with prior reports in other populations, but this is the first such study to focus on AI/AN, and it highlights the importance of considering life course perspectives. Conclusions are limited by the cross-sectional nature of the data. Longitudinal and qualitative work is needed to understand why discrimination may have a stronger effect on mental health for younger than older AI/AN.

Evaluation of DNA damage and stress in wildlife chronically exposed to low-dose, low-dose rate radiation from the Fukushima Dai-ichi Nuclear Power Plant accident.

The health effects associated with chronic low-dose, low-dose rate (LD-LDR) exposures to environmental radiation are uncertain. All dose-effect studies conducted outside controlled laboratory conditions are challenged by inherent complexities of ecological systems and difficulties quantifying dose to free-ranging organisms in natural environments. Consequently, the effects of chronic LD-LDR radiation exposures on wildlife health remain poorly understood and much debated. Here, samples from wild boar (Sus scrofa leucomystax) and rat snakes (Elaphe spp.) were collected between 2016 and 2018 across a gradient of radiation exposures in Fukushima, Japan. In vivo biomarkers of DNA damage and stress were evaluated as a function of multiple measurements of radiation dose. Specifically, we assessed frequencies of dicentric chromosomes (Telomere-Centromere Fluorescence in situ Hybridization: TC-FISH), telomere length (Telo-FISH, qPCR), and cortisol hormone levels (Enzyme Immunoassay: EIA) in wild boar, and telomere length (qPCR) in snakes. These biological parameters were then correlated to robust calculations of radiation dose rate at the time of capture and plausible upper bound lifetime dose, both of which incorporated internal and external dose. No significant relationships were observed between dicentric chromosome frequencies or telomere length and dose rate at capture or lifetime dose (p value range: 0.20-0.97). Radiation exposure significantly associated only with cortisol, where lower concentrations were associated with higher dose rates (r2 = 0.58; p < 0.0001), a relationship that was likely due to other (unmeasured) factors. Our results suggest that wild boar and snakes chronically exposed to LD-LDR radiation sufficient to prohibit human occupancy were not experiencing significant adverse health effects as assessed by biomarkers of DNA damage and stress.

Check your sleep before you start: A secondary analysis of a stress management intervention for caregivers of stem cell transplant patients.

OBJECTIVE: Caregiving for hematopoietic stem cell transplant (HSCT) patients is associated with significant physical and psychological sequelae. While psychosocial interventions may reduce caregiver burden, knowledge regarding which caregivers may benefit the most from such interventions is limited. The purpose of this secondary analysis was to examine whether HSCT caregivers' peritransplant sleep moderated the effect of a psychosocial intervention on depression and anxiety posttransplant. METHODS: Participants included 135 caregivers (mean age = 54.23) who participated in randomized controlled trial and were assigned to receive either 8 weeks of Psychoeducation, Paced Respiration, and Relaxation (PEPRR) or treatment as usual (TAU). Sleep, depression, and anxiety were assessed using the Pittsburg Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, and the State-Trait Anxiety Inventory, respectively. Caregiver symptoms were assessed at baseline (e.g., peritransplant period) and 6-month posttransplant. RESULTS: Baseline sleep quality (∆R2  = 0.04, p = 0.002), sleep efficiency (∆R2  = 0.03, p = 0.02), and sleep onset latency (∆R2  = 0.07, p < 0.001) independently moderated the effect of group assignment on depression outcomes at the 6-month follow-up. Specifically, caregivers with poor sleep at baseline who received PEPRR reported significantly lower depression scores at follow-up compared to caregivers with poor sleep who received TAU. By contrast, only sleep quality (∆R2  = 0.02, p = 0.01) and sleep onset latency (∆R2  = 0.02, p = 0.005) moderated the effect of the group assignment on anxiety. CONCLUSIONS: Psychosocial interventions for HSCT caregivers may buffer against psychological morbidity, particularly among caregivers with poor sleep quality.

A pilot study of mobilized intervention to help caregivers of oncology patients manage distress.

OBJECTIVE: Caregivers of patients with advanced cancer experience significant anxiety, depression, and distress. Caregivers have barriers to accessing in-person treatment to manage stress. Technology allows for the dissemination of evidence-based interventions in a convenient way. This study examined usage rates of Pep-Pal (an evidence-based mobilized intervention to help caregivers of patients with advanced cancer manage distress) and estimates of efficacy on anxiety, depression, stress, and sexual dysfunction. METHODS: Fifty-six primary caregivers of patients with advanced cancer were recruited through oncology clinics and randomized to either Pep-Pal (a mobilized psychoeducation and skills-based intervention for caregivers, n = 26) or treatment as usual (TAU; n = 30). All were screened for moderate anxiety on the Hospital Anxiety and Depression Scale-Anxiety screening assessment (A ≥ 8) at baseline. RESULTS: Participants randomized to Pep-Pal experienced greater reductions in perceived stress (PSS; F = 3.91, p = .05), greater increases in ability to learn and use stress management skills (F = 6.16, p = 0.01), and greater increases in sexual function (women only; F = 5.07, p = 0.03) compared to participants in TAU. Of Pep-Pal participants, only 10 (38.5%) watched at least 7/9 full-length sessions. The a priori hypothesis and criterion that participants would watch at least 75% full-length sessions were not met. CONCLUSIONS: A brief, easily disseminated mobile intervention showed poor adherence, but had limited estimates of efficacy for secondary outcomes; perceived stress, learning stress management skills, and sexual functioning (women only). Future directions are discussed.

Validation of the Brief Perceived Ethnic Discrimination Questionnaire-Community Version in American Indians.

OBJECTIVE: The Brief Perceived Ethnic Discrimination Questionnaire-Community Version (PEDQ-CVB) is a widely used, multidimensional measure of exposure to ethnic/racial discrimination. The PEDQ-CVB has not been previously validated for use with American Indians, who have endured a unique history of colonization, cultural oppression, and ongoing discrimination. This study examined the measurement invariance of the PEDQ-CVB in American Indians (AIs) and 4 other groups. Additional analyses assessed the scale's convergent and discriminant validity and provided initial evidence of associations with mental and physical health in AIs. METHOD: Primary data were collected from a community sample of urban-dwelling AIs (n = 222), which included measures of ethnic/racial identity, other life stressors, and mental and physical health, along with the PEDQ-CVB. These were supplemented by secondary analysis of PEDQ-CVB data from African Americans (n = 1176), Latinos (n = 564), East Asian Americans (n = 274), and South Asian Americans (n = 242). RESULTS: The PEDQ-CVB demonstrated measurement invariance across the 5 ethnic/racial groups and convergent and discriminant validity in AIs. The PEDQ-CVB was significantly associated with depressive symptoms and physical limitations in AIs, after controlling for relevant demographics. CONCLUSION: This study provides strong evidence that the PEDQ-CVB behaves consistently for AIs and other underrepresented ethnic/racial groups. As such, the PEDQ-CVB allows for documentation of the experiences of different ethnic/racial groups and provides a means to test theoretical models of the antecedents and consequences of perceived discrimination within and across groups. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of a nutritional supplement during gestation and early childhood on child salivary cortisol, hair cortisol, and telomere length at 4-6 years of age: a follow-up of a randomized controlled trial.

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4-6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4-6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children (n = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4-6 years. Trial registration: ClinicalTrials.gov Identifier NCT00970866.Lay SummaryThis study addressed a research gap about whether improved nutrition during pregnancy and early childhood impacts telomere length and cortisol in preschool children. There was no difference in child telomere length or cortisol between two trial arms of a nutritional supplementation trial that began during pregnancy. The research outcomes indicate lipid-based nutrient supplements, a relatively new form of supplementation, do not have an effect on markers of stress or cellular aging measured in later childhood.

Perceived stress, psychological resilience, hair cortisol concentration, and metabolic syndrome severity: A moderated mediation model.

BACKGROUND: Psychological resilience is considered to protect against detrimental effects of perceived stress on cardiovascular and metabolic health, but few studies have tested biological mechanisms underlying these relationships. PURPOSE: This study examined whether psychological resilience moderated the indirect association of perceived stress with Metabolic Syndrome (MetS) severity via hair cortisol concentration (HCC), a retrospective index of hypothalamic pituitary adrenal (HPA) axis activity. METHOD: Participants included 228 adults (73 White, 86 Hispanic, 69 African American; mean age 45.29 years; 68% females). Participants completed questionnaires assessing perceived stress (Perceived Stress Scale) and resilience (Brief Resilience Scale). The first 3 cm of scalp-near hair were analyzed for cortisol concentration using enzyme-linked immunoassay analysis. Cardiometabolic risk factors including blood glucose, lipids, blood pressure, and waist circumference were assessed, from which a sex- and race/ethnicity-specific continuous MetS severity score was calculated. A moderated mediation model was tested using path analysis. RESULTS: Psychological resilience moderated the association of perceived stress with HCC (R2 change for interaction = 0.014, p =  0.043), such that the association of perceived stress and HCC decreased as resilience scores increased. Resilience also moderated the indirect association of perceived stress with MetS severity via HCC (b = -0.039, 95% CI [-0.001; -0.100]), such that HCC mediated the association of greater perceived stress with greater MetS severity only for individuals reporting Brief Resilience Scale scores 3 or below (range: 1.17-5.00). Psychological resilience was also associated with lower MetS severity (ß = -0.227, p =  0.014) independent of perceived stress and HCC. CONCLUSION: Findings suggest that psychological resilience may serve as both a stress buffer and as a direct determinant of cardiometabolic health. These results extend literature on psychological resilience to measures of retrospective HPA axis function and MetS severity in a diverse sample.

Race moderates the association of perceived everyday discrimination and hair cortisol concentration.

The influence of discrimination on hypothalamic-pituitary-adrenal (HPA) axis function is considered to be more pronounced for racial minority versus majority groups, although empirical support for this argument is not strong. This study examined whether the association of perceived discrimination was more strongly associated with long-term, retrospective cortisol output (as measured by hair cortisol concentration [HCC]) among African American compared to White adults. Participants included 141 community-dwelling adults (72 White, 69 African American; mean age 45.8 years; 67% females). The Everyday Discrimination Scale assessed perceived discrimination. The first 3 cm of proximal scalp hair was analyzed for HCC using enzyme-linked immunoassay. Associations between race, perceived discrimination and HCC were examined using hierarchical multiple regression. African Americans had higher HCC than Whites, but both groups reported perceived discrimination with similar frequency. Race moderated the association between perceived discrimination and HCC (R2 interaction = 0.03, p = 0.007) such that perceived discrimination was positively associated with HCC among African Americans (ß = 0.28, p = 0.007), but not Whites (ß = -0.11, p = 0.274). Perceived discrimination did not mediate the association between race and HCC (ß for indirect effect = 0.025, 95% CI [-.003, 0.087]). Although perceived discrimination did not differ between races, perceived discrimination was positively associated with retrospective levels of cortisol in scalp hair among African Americans but not Whites. This may suggest that characteristics of discrimination other than frequency are particularly salient to HPA axis function among African Americans (e.g. attribution, severity, historical context).LAY SUMMARYThis study found that greater perceived discrimination frequency was associated with greater long-term cortisol secretion (i.e. hair cortisol concentration) among African American compared to White adults. Both groups reported similar discrimination frequency, so the uniqueness of African Americans' experience with discrimination may be salient to HPA axis upregulation for this population.

Perinatal Food Insecurity and Postpartum Psychosocial Stress are Positively Associated Among Kenyan Women of Mixed HIV Status.

Stress and food insecurity (FI) are associated with poor perinatal and HIV outcomes. We hypothesized that FI would increase postpartum stress among women in Kenya, and that the impact would be greater in women with HIV. Among 371 pregnant women, we identified latent FI trajectories across the perinatal period, and estimated their association with postpartum stress. Stress metrics included the Perceived Stress Scale (PSS) and hair cortisol concentrations (HCC). We identified two FI trajectories: persistent moderate FI and persistent mild FI. Moderate FI (vs. mild) was associated with higher PSS; this association was stronger among HIV-negative women. We observed a trend towards higher HCC associated with moderate FI, which did not differ by HIV status. HCC and PSS were not correlated. In summary, moderate FI (vs. mild) was associated with increased stress. The lack of PSS-HCC correlation could reflect different physiological pathways. Interventions to mitigate FI could alleviate postpartum stress.

Correction: Maternal caregivers have confluence of altered cortisol, high reward-driven eating, and worse metabolic health.

[This corrects the article DOI: 10.1371/journal.pone.0216541.].

Maternal caregivers have confluence of altered cortisol, high reward-driven eating, and worse metabolic health.

Animal models have shown that chronic stress increases cortisol, which contributes to overeating of highly palatable food, increased abdominal fat and lower cortisol reactivity. Few studies in humans have simultaneously examined these trajectories. We examined premenopausal women, either mothers of children with a diagnosis of an autism spectrum disorder (n = 92) or mothers of neurotypical children (n = 91). At baseline and 2-years, we assessed hair cortisol, metabolic health, and reward-based eating. We compared groups cross-sectionally and prospectively, accounting for BMI change. Caregivers, relative to controls, had lower cumulative hair cortisol at each time point, with no decreases over time. Caregivers also had stable levels of poor metabolic functioning and greater reward-based eating across both time points, and evidenced increased abdominal fat prospectively (all ps ≤.05), independent of change in BMI. This pattern of findings suggest that individuals under chronic stress, such as caregivers, would benefit from tailored interventions focusing on better regulation of stress and eating in tandem to prevent early onset of metabolic disease, regardless of weight status.

A randomized control trial of stress management for caregivers of stem cell transplant patients: Effect on patient quality of life and caregiver distress.

BACKGROUND: Psychological interventions reduce caregiver distress (CG-distress). Less distress in caregivers may contribute to improved patient quality of life (QoL), but empirical evidence is lacking. Will a caregiver stress management intervention improve patient QoL? METHODS: In this replication study, we randomized 155 allogeneic hematopoietic stem cell transplant (Allo-HSCT) patients and caregivers to PsychoEducation, Paced Respiration, and Relaxation (PEPRR) or enhanced treatment as usual (eTAU). We provided PEPRR over 3 months following transplant. Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) evaluated patient QoL, and CG-distress was based on depressive, anxious, and stress symptoms. Hierarchical linear models tested intervention, time, and interactions as fixed effects with participant as random effects. RESULTS: Patients whose caregivers received PEPRR did not differ on FACT-BMT between baseline and 6 months (mean = +3.74; 95% CI, -3.54 to 11.02) compared with patients of caregivers in eTAU (mean = +3.16; 95% CI, -2.88 to 9.20) even though CG-distress was decreased by PEPRR (mean = -0.23; 95% CI, -0.448 to -0.010) compared with those receiving eTAU (mean = +0.27; 95% CI, 0.033-0.504) at 6 months. CONCLUSIONS: PEPRR reduced CG-distress without affecting their patient's FACT-BMT score. The FACT-BMT may not have distinguished unique psychological changes associated with their caregiver receiving PEPRR.

Impact of a Mobilized Stress Management Program (Pep-Pal) for Caregivers of Oncology Patients: Mixed-Methods Study.

BACKGROUND: Caregivers of patients with advanced diseases are known to have high levels of distress, including depression and anxiety. Recent research has focused on recognizing caregivers in need of psychosocial support to help them manage their distress. Evidenced-based technological interventions have the potential to aid caregivers in managing distress. OBJECTIVE: The objective of our study was to describe caregiver perceptions of the usability and acceptability, and their suggestions for future adaptations, of a mobilized psychoeducation and skills-based intervention. METHODS: This study was a part of a larger trial of a mobilized psychoeducation and skills-based intervention (Psychoeducation and Skills-Based Mobilized Intervention [Pep-Pal]) for caregivers of patients with advanced illness. This substudy used a mixed-methods analysis of quantitative data from all 26 intervention participants and qualitative data from 14 intervention caregivers who completed the Pep-Pal intervention. The qualitative semistructured individual interviews, which we conducted within the first 4 weeks after participants completed the intervention, assessed the acceptability and usability of Pep-Pal. Additionally, the qualitative interviews provided contextual evidence of how the intervention was helpful to interviewees in unanticipated ways. We conducted applied thematic analysis via independent review of transcripts to extract salient themes. RESULTS: Overall, caregivers of patients with advanced cancer deemed Pep-Pal to be acceptable in all Web-based sessions except for Improving Intimacy. Caregivers perceived the program to be of use across the areas they needed and in others that they had not anticipated. Caregiver recommendations of key changes for the program were to include more variety in caregiver actors in sessions, change the title of Improving Intimacy to Improving Relationships, provide an audio-only option in addition to video, and change the format of the mobilized website program to a stand-alone mobile app. CONCLUSIONS: The valuable feedback in key areas from individual interviews will be integrated into the final version of Pep-Pal that will be tested in a fully powered randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03002896; https://clinicaltrials.gov/ct2/show/NCT03002896 (Archived by WebCite at http://www.webcitation.org/76eThwaei).

Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth.

Latent herpes virus reactivation has been demonstrated in astronauts during shuttle (10-16 days) and International Space Station (≥180 days) flights. Following reactivation, viruses are shed in the body fluids of astronauts. Typically, shedding of viral DNA is asymptomatic in astronauts regardless of mission duration; however, in some cases, live/infectious virus was recovered by tissue culture that was associated with atopic-dermatitis or skin lesions during and after spaceflight. Hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes activation during spaceflight occurs as indicated by increased levels of stress hormones including cortisol, dehydroepiandrosterone, epinephrine, and norepinephrine. These changes, along with a decreased cell mediated immunity, contribute to the reactivation of latent herpes viruses in astronauts. Currently, 47/89 (53%) astronauts from shuttle-flights and 14/23 (61%) astronauts from ISS missions shed one or more herpes viruses in saliva/urine samples. Astronauts shed Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and herpes-simplex-1 (HSV-1) in saliva and cytomegalovirus (CMV) in urine. Larger quantities and increased frequencies for these viruses were found during spaceflight as compared to before or after flight samples and their matched healthy controls. The shedding did not abate during the longer ISS missions, but rather increased in frequency and amplitude. These findings coincided with the immune system dysregulation observed in astronauts from shuttle and ISS missions. VZV shedding increased from 41% in space shuttle to 65% in ISS missions, EBV increased 82 to 96%, and CMV increased 47 to 61%. In addition, VZV/CMV shed ≤30 days after ISS in contrast to shuttle where VZV/CMV shed up to 5 and 3 days after flight respectively. Continued shedding of infectious-virus post-flight may pose a potential risk for crew who may encounter newborn infants, sero-negative adults or any immunocompromised individuals on Earth. Therefore, developing spaceflight countermeasures to prevent viral reactivation is essential. Our spaceflight-developed technologies for saliva collection/rapid viral detection have been extended to include clinical applications including zoster patients, chicken pox, post-herpetic neuralgia, multiple sclerosis, and various neurological disorders. These protocols are employed in various clinics and hospitals including the CDC and Columbia University in New York, as well as overseas in Switzerland and Israel.

Distress and quality of life in patient and caregiver dyads facing stem cell transplant: identifying overlap and unique contributions.

PURPOSE: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a demanding treatment requiring caregiver support. The pre-transplant period is particularly stressful. How patient and caregiver dyads respond to these stressors can impact post-transplant outcomes. The purpose of this cross-sectional study was to assess pre-transplant patient and caregiver distress, patient quality of life (pQoL), and simultaneously investigate relationship between caregiver distress, patient distress, and patient QoL. METHODS: We measured caregiver anxiety, depressive symptoms, perceived stress, sleep quality, caregiver burden, and pQoL in148 dyads compared to clinical thresholds or population norms. To reduce comparisons, we created a composite distress score from affective measures. Associations within dyads were examined via correlation and path analysis. RESULTS: Most dyads scored above norms for psychological measures. Patient distress was positively associated with caregiver distress. Higher caregiver distress significantly predicted poorer pQoL after accounting for the interdependence of patient and caregiver distress. Specifically, patients' physical functioning was the primary driver of this interrelationship. CONCLUSIONS: Allo-HSCT patients and their caregivers reported elevated distress pre-transplant. Both patient and caregiver distress contributed to pQoL, with patients' physical functioning accounting significantly for caregiver well-being. Supporting the patient-caregiver dyad before transplantation is a priority for supportive services.