Validity of Partner Reports of Recent Condomless Sex.

BACKGROUND: Prostate-specific antigen (PSA), a biomarker of vaginal semen exposure, is less susceptible to bias than self-reported condom use behaviors. We examined the agreement of self-reported recent condomless sex (RCS) within couples and how these reports related to PSA detection. METHODS: We analyzed data from a study conducted in Vietnam, 2017 to 2020, of 500 different-sex couples using condoms and no other contraceptive method to prevent pregnancy for 6 months. We assessed enrollment and 6-month data from vaginal swabs and questionnaires from both partners. We calculated Prevalence-Adjusted Bias-Adjusted Kappa (PABAK) to evaluate agreement of men's and women's reports. Among couples with detected PSA, we assessed partner concordance of RCS reporting. RESULTS: At enrollment (n = 499), 79.8% of couples reported no RCS, 16.4% reported RCS, and 3.8% had partner-discordant reports (PABAK, 0.93; 95% confidence interval, 0.91-0.97). At 6 months (n = 472), 91.7% reported no RCS, 5.7% reported RCS, and 2.5% had partner-discordant reports (PABAK, 0.98; 95% confidence interval, 0.96-1.0). Among couples with detected PSA at baseline (11%, n = 55), 36% reported no RCS, 55% reported RCS, and 6% had discordant reports; at 6 months (6.6%, n = 31), 58% reported no RCS, 35% reported RCS, and 3% had discordant reports. CONCLUSIONS: We observed high agreement regarding condomless sex within couples in a population using condoms as contraception in Vietnam; however, a high proportion of couples with detected PSA had both partners reporting no RCS, indicating that concordant reporting of no RCS does not indicate lack of semen exposure.

Mental health in society's margins: poor n-3 PUFA intake and psychological well-being of homeless youth.

Dietary intake of long-chain n-3 PUFA (n-3 PUFA), particularly EPA and DHA, has been associated with psychological well-being, but little is known about the n-3 PUFA intake of homeless youth. The current study determined the association between depression and anxiety symptoms and n-3 PUFA intake and erythrocytes status in homeless youth. Totally, 114 homeless youth aged 18-24 years were recruited from a drop-in centre. n-3 PUFA dietary intake was assessed using an FFQ, and erythrocytes status was determined by gas chromatography (GC). Linear regression models were used to determine the relationship between psychological well-being and n-3 PUFA intake and status. The mean intakes of EPA and DHA for all participants (0·06 ± 0·13 g/d and 0·11 ± 0·24 g/d) were well below recommended levels, and mean erythrocytes EPA + DHA (n-3 index) in the cohort (2·42 %) was lower than reported for healthy, housed adolescents and those with clinical depression. There was no association of n-3 PUFA intake and erythrocytes status with either depression or anxiety. However, the relationships of depression with dietary EPA (P = 0·017) and DHA (P = 0·008), as well as erythrocytes DHA (P = 0·007) and n 3-index (P = 0·009), were significantly moderated by sex even after adjusting for confounders. Specifically, among females, as the intake and status of these n-3 PUFA decreased, depression increased. Our findings show poor dietary intake and low erythrocytes status of n-3 PUFA among homeless youth, which is associated with depressive symptoms among females.

Age differences in emotion regulation strategy use and flexibility in daily life.

OBJECTIVES: Age-related shifts in emotion regulation patterns are important for explaining preserved emotional well-being in late adulthood amidst declines in physical and cognitive health. Although several studies have examined age-related shifts in emotion regulation strategy use, age differences in how specific strategies are flexibly adapted to shifting contexts in daily life and the adaptiveness of such shifts remains poorly understood. METHODS: 130 younger adults (ages 22-35) and 130 older adults (ages 65-85) completed a modified Day Reconstruction Method Assessment and self-report questionnaires to examine age differences in emotion regulation strategy use and one aspect of emotion regulation flexibility (responsiveness) in daily life, and the adaptive implications of these differences. RESULTS: Older adults exhibited more frequent acceptance use, less frequent distraction use, and less flexibility in the responsiveness of strategies with varying negative affect. Across age groups, the use of expressive suppression and distraction was associated with less adaptive outcomes, whereas higher acceptance responsiveness, positive reappraisal responsiveness, and situation selection responsiveness were associated with more adaptive outcomes. Age-group moderated the associations between adaptiveness metrics with the use and flexibility of several emotion regulation strategies. CONCLUSION: The current findings provide early evidence of age-related decreases in emotion regulation flexibility as well as age-related shifts in the adaptiveness of emotion regulation patterns.

Typhoid vaccine does not impact feelings of social connection or social behavior in a randomized crossover trial among middle-aged female breast cancer survivors.

BACKGROUND: Inflammation can have social consequences, which may be relevant to inflammation's link with depression. The current study tests whether a typhoid vaccine increases feelings of social disconnection and avoidance behavior. METHOD: In two full-day visits at least three weeks apart, 172 postmenopausal breast cancer survivors (Stage I-IIIA) each received a typhoid capsular polysaccharide vaccination and a saline placebo injection in a random sequence. Blood was drawn prior to the injection, as well as every 90 min thereafter for 8 h to assess the inflammatory response (interleukin-6, IL-6; interleukin-1 receptor antagonist, IL-1Ra). At both visits, women completed the Social Connection Scale at 0 and 8.5 h post-vaccination as well as implicit and explicit social avoidance tasks at 7 h post-vaccination. RESULTS: The typhoid vaccine triggered rises in both inflammatory markers (ps < 0.01), but it did not impact feelings of social connection (p = .32), or performance on the implicit (p = .34) or explicit tasks (p = .37). Inflammatory rises did not predict feelings of social connection (ps > 0.64) or performance on explicit (ps > 0.73) or implicit (ps > 0.88) social avoidance tasks. CONCLUSION: Milder inflammatory stimuli may not affect social processes. Higher levels of inflammation or, relatedly, more sickness symptoms may be necessary to recapitulate prior findings of social avoidance.

Worry and Mindfulness Differentially Impact Symptom Burden Following Treatment Among Breast Cancer Survivors: Findings From a Randomized Crossover Trial.

BACKGROUND: Breast cancer survivors often experience many somatic and cognitive side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers opportunities to either enhance or dampen physical health. PURPOSE: In a secondary analysis of a double-blind randomized controlled trial (RCT) using a typhoid vaccine to assess factors associated with breast cancer survivors' inflammatory responses, we assessed how two specific aspects of emotion regulation, mindfulness, and worry, corresponded to acute changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. METHODS: Breast cancer survivors (N = 149) completed two 8.5-hr visits at a clinical research center. Survivors were randomized to either the vaccine/saline placebo or a placebo/vaccine sequence. Worry and mindfulness questionnaires provided data on trait-level emotion regulation abilities. Fatigue, memory problems, and focus difficulties were assessed via Likert scales six times-once before the injections and then every 90 min for 7.5 hr thereafter. Women also completed a pain sensitivity task and several cognitive tasks at each visit. RESULTS: Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits and irrespective of injection type. Lower mindfulness also corresponded to higher subjective fatigue and hot pain sensitivity and objective ratings. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. CONCLUSION: Results from this study highlight the benefits of adaptive emotion regulation in helping mitigate symptoms associated with breast cancer survivorship.

Breast cancer survivors experience side effects resulting from their cancer diagnosis and treatment, including higher rates of pain, fatigue, and memory/concentration problems. Emotion regulation offers the possibility to either better or worse physical health. This study assessed how two emotion regulation strategies, mindfulness and worry, corresponded to changes in focus problems, memory problems, and fatigue along with performance on pain sensitivity and cognitive tasks across two visits among breast cancer survivors. A total of 149 survivors completed 2 day-long visits in the laboratory where they rated their fatigue and memory problems six times across the day, completed cognitive tests, and a pain sensitivity test. Findings from this study showed that breast cancer survivors who worried more and were less mindful experienced subjective memory problems, focus problems, and cold pain sensitivity across two visits. Emotion regulation skills did not predict objective pain sensitivity or cognitive problems. Results from this study highlight the benefits of adaptive emotion regulation skills like mindfulness in helping improve the cognitive and physical symptoms commonly experienced by breast cancer survivorship.

Early Developmental Trends in High-Risk Neonates Later Diagnosed With Autism Spectrum Disorder.

PURPOSE: We hypothesized that clinical data from a neonatal intensive care unit (NICU) infant developmental follow-up clinic would identify early manifestations of autism spectrum disorder (ASD). METHODS: One hundred forty-four infants were identified; 72 later diagnosed with ASD and 72 controls. Retrospective chart review provided data from the Test of Infant Motor Performance (TIMP) and the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), between 8 and 26 months of age. RESULTS: Between-group comparisons indicated no significant group difference in TIMP scores; however, Bayley-III scaled scores differed between the groups at 2 administration times. The within-group Bayley-III change scores declined significantly more for the ASD group in cognitive and communication subtests. CONCLUSION: High-risk neonates, due to prematurity or morbidity, later diagnosed with ASD demonstrated statistically significant differences, including a more precipitous drop in Bayley-III scores over time. Early, longitudinal developmental surveillance for neonates at risk of ASD is critical. What this adds to the evidence: Early identification of ASD is critical to optimize developmental outcomes in young children, including infants born prematurely or with neonatal morbidity, who are perceived to have an increased risk for ASD. Despite these findings, minimal research has been conducted to evaluate the utility of commonly administered norm-referenced developmental surveillance instruments to identify possible early signs of ASD in this high-risk population due to prematurity or neonatal morbidity and not familial association. The present study analyzed retrospectively collected clinical data from a NICU developmental follow-up clinic for 144 infants, 72 of which were later diagnosed with ASD and 72 sex- and gestational age-matched controls. Results demonstrated statistically significant poorer Bayley-III outcomes for the ASD group compared with controls at 2 different study time points, including a more precipitous drop in Bayley-III scaled scores over time. This study highlights the importance of early and longitudinal developmental surveillance for high-risk neonates at risk of ASD.

Frequent Interpersonal Stress and Inflammatory Reactivity Predict Depressive-Symptom Increases: Two Tests of the Social-Signal-Transduction Theory of Depression.

The social-signal-transduction theory of depression asserts that people who experience ongoing interpersonal stressors and mount a greater inflammatory response to social stress are at higher risk for depression. The current study tested this theory in two adult samples. In Study 1, physically healthy adults (N = 76) who reported more frequent interpersonal tension had heightened depressive symptoms at Visit 2, but only if they had greater inflammatory reactivity to a marital conflict at Visit 1. Similarly, in Study 2, depressive symptoms increased among lonelier and less socially supported breast-cancer survivors (N = 79). This effect was most pronounced among participants with higher inflammatory reactivity to a social-evaluative stressor at Visit 1. In both studies, noninterpersonal stress did not interact with inflammatory reactivity to predict later depressive symptoms.

Breast cancer survivors' typhoid vaccine responses: Chemotherapy, obesity, and fitness make a difference.

PURPOSE: To investigate breast cancer survivors' inflammatory responses to typhoid vaccine as a window into their innate immune response to novel pathogens. METHODS: This double-blind crossover trial randomized 158 breast cancer survivors to either the vaccine/saline placebo or the placebo/vaccine sequence. The relative contributions of age, cardiorespiratory fitness (VO2peak), type of cancer treatment, central obesity, and depression to interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and WBC vaccine responses were assessed pre-injection and 1.5, 3, 4.5, 6, and 7.5 h post-injection. RESULTS: The vaccine produced larger IL-6, IL-1Ra, and WBC responses than placebo, ps < 0.0001. Prior chemotherapy, higher central obesity, and lower VO2peak were associated with smaller vaccine responses after controlling for baseline inflammation. Vaccine response was summarized by the percent increase in area under the curve (IL-6, WBC) or average post-injection mean (IL-1Ra) for vaccine relative to placebo. Women who received chemotherapy had smaller vaccine responses than women who did not for both IL-6 (44% vs 78%, p <.001) and WBC (26% vs 40%, p <.001); IL-1ra response was not significantly moderated by chemotherapy. Women whose central adiposity was one standard deviation above the mean had smaller vaccine responses than women with average adiposity for IL-6 (33% vs 54%, p <.001), WBC (20% vs 30%, p <.001), and IL-1Ra (2.0% vs 3.2%, p <.001). Women with an average level of VO2peak had smaller vaccine responses than women whose VO2peak was one standard deviation above the mean for IL-6 (54% vs 73%, p <.001), WBC (30% vs 40%, p <.001), and IL-1Ra (3.2% vs. 4.1%, p = 0.01). Age and depression did not significantly moderate vaccine responses. CONCLUSIONS: This study provided novel data on chemotherapy's longer-term adverse immune consequences. The data also have an important public health message: even relatively low levels of fitness can benefit the innate immune response to a vaccine.

Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults.

Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.

Effects of plant-based versus marine-based omega-3 fatty acids and sucrose on brain and liver fatty acids in a mouse model of chemotherapy.

Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial).

BACKGROUND: Mindfulness meditation is a form of mind-body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial-HealthyAgers trial-that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults. METHODS: One hundred fifty older adults (ages 65-85 years) will be randomized into one of two groups: an eight-week mindfulness program or an eight-week, placebo-controlled, lifestyle education program. Behavioral and neuroimaging assessments are conducted before and after the training. Participants are then invited to booster sessions once every three months for a period of 12 months with post-intervention follow-up assessments conducted at 6-months and 12-months. The primary outcomes for the study are behavioral measures of attentional control and mind-wandering. Additional, secondary outcomes include network strength in an a priori defined neuromarker of attentional control, fluid and everyday cognition, emotion regulation strategy use, and markers of inflammation. DISCUSSION: This study will establish the efficacy of a group-based, low-cost mind-body intervention for the inter-related facets of attentional control and mind-wandering in older adults. Strengths of this study include a well-designed, placebo-controlled comparison group, use of web/mobile application to track study adherence, and longitudinal follow-up. TRIAL REGISTRATION: Clinicaltrials.gov (# NCT03626532 ). Registered August 4, 2018.

Impact of mindfulness training on in-the-moment attentional control and emotion dysregulation in older adults: secondary analysis of a pilot, placebo-controlled randomized controlled trial.

Mindfulness-based interventions show increasing promise for improving attention and emotion regulation- processes that critically support healthy aging. Given their complex, multi-faceted nature, identifying specific aspects of attention and emotion regulation that are modifiable with training in older adults, particularly compared with active control groups, is an ongoing challenge. We performed pre-registered, secondary analyses of a pilot randomized controlled trial comparing the effects of a four-week mindfulness-based attention training (MBAT) group and a lifestyle education (LifeEd) active control group on attention and emotion dysregulation in older adults. Differential training outcomes were assessed for: (a) in-the-moment effects of mind-wandering on sustained attention, measured by performance decrements preceding self-reported mind-wandering, and (b) self-reported emotion dysregulation. Baseline working memory (WM) performance was tested as a moderator of training effects. There were no significant between-group differences for change in in-the-moment effects of mind-wandering on attention or emotion dysregulation. However, baseline WM moderated training effects, such that older adults with higher WM showed greater reductions in emotion dysregulation following mindfulness training. This has potential implications for identifying aging cohorts that may benefit most from this type of training.

Factors associated with parenting stress in parents of 18-month-old children: Parenting stress in parents of toddlers.

AIM: Parenting stress is associated with less optimal outcomes for children. Risk factors contributing to parenting stress in healthy toddlers have received little empirical attention. This study sought to determine the factors that are associated with parenting stress in parents of 18-month-old children. METHODS: We analysed cross-sectional survey data from a prospective cohort study focused on parent-child mealtime interactions. Families with an 18-month-old child were recruited in Columbus, Ohio, USA, between December 2017 and May 2019. Adjusted stepwise linear regression models estimated associations between child factors (e.g., temperament), parental factors (e.g., depressive symptoms), quality of romantic relationship factors (e.g., adult attachment style) and home environment factors (e.g., household income) and parenting stress (Parental Distress subscale of the Parenting Stress Index-4 Short Form). RESULTS: The 299 children included 129 (43%) females. Parents were on average 30.6 (SD 6.1) years old and included a diverse racial/ethnic cohort. Mean Parental Distress score was 24.3 (SD 6.8; score range 12-60). Higher Parental Distress scores were associated with greater parental depressive symptoms (B = 5.1 [95% CI: 2.4, 7.7]) and avoidant (B = 2.8 [95% CI: 0.9, 4.6]) attachment style. Other child, parental and home environment factors did not demonstrate statistically significant relationships with parental distress in the final model. CONCLUSION: Our findings align with recommendations for paediatric providers to screen for parenting stress and mental health.

Sugars measured enzymatically in a fasting overnight urine sample are not sensitive biomarkers of dietary added sugar intake in postmenopausal women.

BACKGROUND: Restricting dietary sugar is a leading recommendation, but limited biomarkers assessing intake exist. Although 24-h urinary sucrose (U-Suc) and urinary fructose (U-Fruc) excretion has been used with mixed success, collection is burdensome. AIM: This study aimed to test the sensitivity of an enzymatic assay of U-Suc and U-Fruc to detect changing added sugar intake using low-burden overnight urine samples in 30 postmenopausal women. METHODS: Women consumed usual dietary intake during day 1 and usual intake plus a sugar sweetened beverage during day 2. Weighed, photographed food records assessed intake. Enzymatic assay measured U-Suc and U-Fruc from fasting overnight samples; liquid chromatography mass spectrometry (LC-MS) validated U-Suc findings. RESULTS: Dietary added sugars increased significantly during day 2 (p < 0.001), but urinary sugars were not significantly increased. Enzymatic assay detected urinary sugars in 75% (U-Suc) and 35% (U-Fruc) of samples. Dietary sucrose was not associated with U-Suc, however dietary fructose was significantly associated with U-Fruc [ß = 0.031; p < 0.05] among women with detectable urinary sugars. Participants with detectable U-Fruc consumed more energy from added sugars [12.6% kcal day 1; 21.5% kcal day 2] than participants with undetectable U-Fruc [9.3% kcal day 1; 17.4% kcal day 2], p < 0.05. Using LC-MS, U-Suc predicted sucrose and added sugar intake [ß = 0.017, ß = 0.013 respectively; both p < 0.05]. CONCLUSIONS: Urinary sugars measured enzymatically from overnight urine samples were not sensitive biomarkers of changing added sugar intake in postmenopausal women. However, urinary fructose measured by enzymatic assay or LC-MS may differentiate low versus high added sugar consumers.

Erythrocyte Long-Chain ω-3 Fatty Acids Are Positively Associated with Lean Mass and Grip Strength in Women with Recent Diagnoses of Breast Cancer.

BACKGROUND: Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. OBJECTIVES: The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. METHODS: This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. RESULTS: The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (ß = 0.015, P = 0.01) and grip strength (ß = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. CONCLUSIONS: The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.

Childhood abuse histories predict steeper inflammatory trajectories across time.

BACKGROUND: The Center for Disease Control (CDC) recently named childhood abuse histories as a public health risk. Clear links between abuse histories and inflammation exist. However, it remains unknown how abuse histories impact inflammatory trajectories throughout adulthood. Accordingly, this study assessed inflammatory trajectories across three visits among healthy adults with and without abuse histories. METHOD: In this secondary analysis of data from a longitudinal observational study of cancer survivors and noncancer controls, 157 noncancer controls (Mage = 55.8, range = 32-83) completed the Childhood Experiences Questionnaire (CTQ), providing data on physical, emotional, and sexual abuse prior to age 18. Cytokines interleukin-6 (IL-6), interleukin 1-beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were collected at the baseline visit and two follow-up visits approximately one (M months = 11.52, SD = 4.10) and two years (M months = 23.79, SD = 4.40) later. To represent inflammatory changes, cytokine data at each visit were combined into a composite z-score. Covariates in all analyses included age, biological sex, race, income, body mass index, menopause status, psychological diagnosis history, and medical comorbidities. RESULTS: Compared to their nonabused peers, those who had experienced any type of abuse in childhood demonstrated steeper rises in inflammation across time. Inflammation rose more steeply for individuals with physical and emotional abuse histories compared to those without such histories. CONCLUSION: Overall, these data suggest that childhood abuse histories may quicken age-related increases in inflammation, contributing to accelerated aging, morbidity, and early mortality. These findings provide mechanistic insight into why child abuse is a public health risk.

A mixed methods analysis of environmental and household chaos: considerations for early-childhood obesity research.

BACKGROUND: Chaos has implications for child health that may extend to childhood obesity. Yet, results from studies describing associations between chaos and childhood obesity are mixed. New approaches to studying the environments of young children may help to clarify chaos-obesity relationships. METHODS: We conducted a concurrent mixed methods analysis of quantitative and qualitative data describing home and neighborhood chaos among a diverse cohort of 283 caregiver-toddlers dyads from Ohio. We examined the underlying structure of environmental and household chaos using exploratory factor analysis then sought to validate the structure using qualitative field notes. We generated total scores for factors of chaos and described their distributions overall and according to cohort characteristics. Additionally, we conducted a thematic content analysis of brief ethnographies to provide preliminary construct validity for our indicators of chaos. RESULTS: Dyads varied according to household composition, income, education, and race/ethnicity. We found evidence for a multi-factor structure for chaos, which included disorganization and neighborhood noise. Household disorganization scores ranged from 0 to 7.3 and were on average 2.1 (SD = 1.8). Neighborhood noise scores ranged from 0 to 4 and were on average 1.1 (SD = 1.1). Both disorganization and neighborhood noise were associated with indicators of socioeconomic disadvantage, such as lower educational attainment and household income. Qualitative data from households with high and low scores on the two identified factors were aligned in ways that were supportive of construct validity and further contextualized the social and material environments in which chaos occurred. CONCLUSIONS: Chaos represents a complex construct with implications spanning various disciplines, including childhood obesity research. Previous studies suggest challenges associated with measuring chaos may limit the conclusions that can be drawn about which aspect of chaos (if any) matter most of early childhood weight development. We advance the literature by demonstrating chaos may be comprised of conceptually distinct subdomains. Future childhood obesity prevention research may benefit from more contemporary measure of chaos, such as those relying on direct observations that account for a multifaceted underlying structure.

Multiple imputation by predictive mean matching in cluster-randomized trials.

BACKGROUND: Random effects regression imputation has been recommended for multiple imputation (MI) in cluster randomized trials (CRTs) because it is congenial to analyses that use random effects regression. This method relies heavily on model assumptions and may not be robust to misspecification of the imputation model. MI by predictive mean matching (PMM) is a semiparametric alternative, but current software for multilevel data relies on imputation models that ignore clustering or use fixed effects for clusters. When used directly for imputation, these two models result in underestimation (ignoring clustering) or overestimation (fixed effects for clusters) of variance estimates. METHODS: We develop MI procedures based on PMM that leverage these opposing estimated biases in the variance estimates in one of three ways: weighting the distance metric (PMM-dist), weighting the average of the final imputed values from two PMM procedures (PMM-avg), or performing a weighted draw from the final imputed values from the two PMM procedures (PMM-draw). We use Monte-Carlo simulations to evaluate our newly proposed methods relative to established MI procedures, focusing on estimation of treatment group means and their variances after MI. RESULTS: The proposed PMM procedures reduce the bias in the MI variance estimator relative to established methods when the imputation model is correctly specified, and are generally more robust to model misspecification than even the random effects imputation methods. CONCLUSIONS: The PMM-draw procedure in particular is a promising method for multiply imputing missing data from CRTs that can be readily implemented in existing statistical software.

Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.

PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.

Imputing estrogen receptor (ER) status in a population-based cancer registry: a sensitivity analysis.

Breast cancers are clinically heterogeneous based on tumor markers. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program provides baseline data on these tumor markers for reporting cancer burden and trends over time in the US general population. These tumor markers, however, are often prone to missing observations. In particular, estrogen receptor (ER) status, a key biomarker in the study of breast cancer, has been collected since 1992 but historically was not well-reported, with missingness rates as high as 25% in early years. Previous methods used to correct estimates of breast cancer incidence or ER-related odds or prevalence ratios for unknown ER status have relied on a missing-at-random (MAR) assumption. In this paper, we explore the sensitivity of these key estimates to departures from MAR. We develop a predictive mean matching procedure that can be used to multiply impute missing ER status under either an MAR or a missing not at random assumption and apply it to the SEER breast cancer data (1992-2012). The imputation procedure uses the predictive power of the rich set of covariates available in the SEER registry while also allowing us to investigate the impact of departures from MAR. We find some differences in inference under the two assumptions, although the magnitude of differences tends to be small. For the types of analyses typically of primary interest, we recommend imputing SEER breast cancer biomarkers under an MAR assumption, given the small apparent differences under MAR and missing not at random assumptions. Copyright © 2016 John Wiley & Sons, Ltd.