Type I interferons, inflammation, and fatigue in a longitudinal RNA study of women with breast cancer.

BACKGROUND: Fatigue is a common side effect of cancer and its treatment and is thought to be driven in part by activation of the proinflammatory cytokine network. However, the cellular and molecular underpinnings of cancer-related fatigue (CRF) have not been determined, nor have immune pathways beyond inflammation been carefully investigated. The goal of this study was to examine the association between CRF and activation of canonical proinflammatory gene regulation pathways and Type I interferon (IFN) signaling pathways in breast cancer patients during and after treatment. METHODS: Women diagnosed with early-stage breast cancer (n = 181) completed assessments before and after treatment with radiation and/or chemotherapy and at 6, 12, and 18-month post-treatment follow-ups. Assessments included self-reported fatigue (Multidimensional Fatigue Symptom Inventory - Short Form) and expression of pre-specified sets of Type I IFN and pro-inflammatory immune response genes determined from mRNA sequencing of PBMCs. Mixed effect linear models examined changes in fatigue and immune gene expression over time and tested the hypothesis that fatigue would be associated with increased expression of Type I IFN and inflammatory response genes. RESULTS: There were significant changes in fatigue and immune gene expression across the assessment period; all measures increased from pre- to post-treatment but showed diverging patterns over the follow-up, with declines in fatigue and persistent elevations in Type I IFN and proinflammatory gene expression. In mixed effect linear models, expression of Type I IFN response genes was elevated in association with fatigue across the assessment period, from pre-treatment to 18-month follow-up. In contrast, pro-inflammatory gene expression was associated with fatigue only at 6, 12, and 18-month follow-ups. Analyses controlling for changes in leukocyte subsets continued to show a significant association between fatigue and Type I IFN gene expression but reduced the time-dependent association with pro-inflammatory gene expression to non-significant. CONCLUSIONS: Results revealed unexpected complexity in the immune underpinnings of CRF and identify a novel role for IFN signaling as a robust contributor to this symptom before, during, and after treatment. Pro-inflammatory gene expression emerged as a predictor of fatigue later in the cancer trajectory, and that effect was primarily accounted for by a concurrent increase in monocyte prevalence.

Work Productivity Among Younger Breast Cancer Survivors: The Impact of Behavioral Interventions for Depression.

OBJECTIVES: The Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms. METHODS: The Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss. RESULTS: Of 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity. CONCLUSIONS: These findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs.

International study of childhood leukemia in residences near electrical transformer rooms.

OBJECTIVES: New epidemiologic approaches are needed to reduce the scientific uncertainty surrounding the association between extremely low frequency magnetic fields (ELF-MF) and childhood leukemia. While most previous studies focused on power lines, the Transformer Exposure study sought to assess this association using a multi-country study of children who had lived in buildings with built-in electrical transformers. ELF-MF in apartments above built-in transformers can be 5 times higher than in other apartments in the same building. This novel study design aimed to maximize the inclusion of highly exposed children while minimising the potential for selection bias. METHODS: We assessed associations between residential proximity to transformers and risk of childhood leukemia using registry based matched case-control data collected in five countries. Exposure was based on the location of the subject's apartment relative to the transformer, coded as high (above or adjacent to transformer), intermediate (same floor as apartments in high category), or unexposed (other apartments). Relative risk (RR) for childhood leukemia was estimated using conditional logistic and mixed logistic regression with a random effect for case-control set. RESULTS: Data pooling across countries yielded 16 intermediate and 3 highly exposed cases. RRs were 1.0 (95% CI: 0.5, 1.9) for intermediate and 1.1 (95% CI: 0.3, 3.8) for high exposure in the conditional logistic model. In the mixed logistic model, RRs were 1.4 (95% CI: 0.8, 2.5) for intermediate and 1.3 (95% CI: 0.4, 4.4) for high. Data of the most influential country showed RRs of 1.1 (95% CI: 0.5, 2.4) and 1.7 (95% CI: 0.4, 7.2) for intermediate (8 cases) and high (2 cases) exposure. DISCUSSION: Overall, evidence for an elevated risk was weak. However, small numbers and wide confidence intervals preclude strong conclusions and a risk of the magnitude observed in power line studies cannot be excluded.

Developing and Evaluating a School-Based Tobacco and E-Cigarette Prevention Program for Deaf and Hard-of-Hearing Youth.

School-based programs are an important tobacco prevention tool. Yet, existing programs are not suitable for Deaf and Hard-of-Hearing (DHH) youth. Moreover, little research has examined the use of the full range of tobacco products and related knowledge in this group. To address this gap and inform development of a school-based tobacco prevention program for this population, we conducted a pilot study among DHH middle school (MS) and high school (HS) students attending Schools for the Deaf and mainstream schools in California (n = 114). American Sign Language (ASL) administered surveys, before and after receipt of a draft curriculum delivered by health or physical education teachers, assessed product use and tobacco knowledge. Thirty-five percent of students reported exposure to tobacco products at home, including cigarettes (19%) and e-cigarettes (15%). Tobacco knowledge at baseline was limited; 35% of students knew e-cigarettes contain nicotine, and 56% were aware vaping is prohibited on school grounds. Current product use was reported by 16% of students, most commonly e-cigarettes (12%) and cigarettes (10%); overall, 7% of students reported dual use. Use was greater among HS versus MS students. Changes in student knowledge following program delivery included increased understanding of harmful chemicals in tobacco products, including nicotine in e-cigarettes. Post-program debriefings with teachers yielded specific recommendations for modifications to better meet the educational needs of DHH students. Findings based on student and teacher feedback will guide curriculum development and inform next steps in our program of research aimed to prevent tobacco use in this vulnerable and heretofore understudied population group.

Effectiveness and feasibility of three types of parent reminders to increase adolescent human papillomavirus (HPV) vaccination.

Parent reminders have produced modest improvements in human papillomavirus (HPV) vaccination among adolescents. However, little prior research has compared the effectiveness and feasibility of different HPV reminder types in resource-limited settings. We conducted a quasi-experimental study (2016-2017) to evaluate the effectiveness of three parent reminder types (mailed letters, robocalls, text messages) on next-dose HPV vaccine receipt among 12-year-olds in a large Federally Qualified Health Center in Los Angeles County. Six clinics were matched into three pairs: randomly assigning one clinic within each pair to intervention and control. Intervention clinics were randomly assigned to deliver one of the three parent reminder types. We calculated rates of next-dose vaccine receipt and assessed intervention effects using logistic regression models. We calculated the proportion of each type of reminder successfully delivered as a feasibility measure. The study sample comprised 877 12-year-olds due for an HPV vaccine dose (47% female, >85% Latino). At 4-month follow-up, 23% of intervention patients received an HPV vaccine dose compared to only 12% of control patients. Overall, receipt of any reminder increased rates of the next-needed HPV vaccine compared to usual care (p = 0.046). Significant improvements were observed for text reminders (p = 0.036) and boys (p = 0.006). Robocalls were the least feasible reminder type. Text message reminders are feasible and effective for promoting HPV vaccination. Future research is needed to assess the effectiveness and feasibility of reminders compared to other vaccine promotion strategies.

Psychosocial Resilience to Inflammation-Associated Depression: A Prospective Study of Breast-Cancer Survivors.

Stress can lead to depression, in part because of activation of inflammatory mechanisms. It is therefore critical to identify resilience factors that can buffer against these effects, but no research to date has evaluated whether psychosocial resilience mitigates the effects of stress on inflammation-associated depressive symptoms. We therefore examined psychosocial resources known to buffer against stress in a longitudinal study of women with breast cancer (N = 187). Depressive symptoms and inflammation were measured over a 2-year period extending from after diagnosis into survivorship. Cancer-related stress and psychosocial resources-social support, optimism, positive affect, mastery, self-esteem, and mindfulness-were measured after diagnosis. As hypothesized, women who reported having more psychosocial resources showed weaker associations between stress and depressive symptoms and weaker associations between stress and inflammation-related depressive symptoms. Results highlight the importance of psychosocial resilience by demonstrating a relationship between psychosocial resources and sensitivity to inflammation-associated depressive symptoms.

Socioeconomic Status and Inflammation in Women with Early-stage Breast Cancer: Mediation by Body Mass Index.

BACKGROUND: Breast cancer is the most common cancer among women in the US, and women of low socioeconomic status (SES) show markedly poorer outcomes than those of high SES. SES may influence health through inflammation, although links between SES and inflammatory biomarkers have not been investigated in women with breast cancer. This study tested the hypothesis that breast cancer patients of lower SES would show higher levels of inflammation than those of higher SES. BMI was examined as a mediator of this association. METHODS: Women recently diagnosed with early-stage breast cancer (N = 194) were recruited before neoadjuvant or adjuvant therapy. Participants completed questionnaires and provided blood samples for immune assessment. SES was indexed by participants' self-reported education and annual household income, BMI was determined by height and weight measurements, and blood was assayed for inflammatory biomarkers linked with cancer outcomes: IL-6, CRP, TNF-α, and sTNF-RII. General linear models tested associations between SES and inflammation, and mediation models examined indirect effects through BMI. RESULTS: Consistent with hypotheses, education status was associated with CRP, (F(2,185) = 4.72, p = 0.001), and sTNF-RII, (F(2,185) = 4.19, p = 0.02), such that lower education was associated with higher levels of both biomarkers. Further, BMI mediated the associations between education and CRP, (95% CIs [-0.62, -0.11; -0.76, -0.21]), sTNF-RII, (95% CIs [-0.09, -0.01; -0.10, -0.02]), and IL-6, (95% CIs [-0.32, -0.05; -0.38, -0.09]). Annual household income was not significantly associated with inflammation (ps > 0.25), and indirect effects on inflammation through BMI were not significant. CONCLUSIONS: Lower education was associated with higher levels of inflammation in this sample, which may presage poor breast cancer-related and clinical outcomes. SES should inform the development of interventions targeting BMI and inflammation in breast cancer.

Power analysis for stepped wedge trials with multiple interventions.

Stepped wedge design (SWD) trials are cluster randomized trials that feature staggered, unidirectional cross-over between treatment conditions. Existing literature on power for SWDs focuses primarily on designs with two conditions, typically a control and an intervention condition. However, SWDs with more than one treatment condition are being proposed and conducted. We present a linear mixed model for SWDs with two or more interventions, including both multiarm and factorial designs. We derive standard errors of the intervention effect coefficients, and present power calculation methods. We consider both repeated cross-sectional and cohort designs. Design features, with a focus on treatment allocations, are examined to determine their impact on power.

Randomized Controlled Pilot Trial of a Low-Touch Remotely-Delivered Values Intervention to Promote Adherence to Adjuvant Endocrine Therapy Among Breast Cancer Survivors.

BACKGROUND: Oral anti-cancer treatments such as adjuvant endocrine therapies (AET) for breast cancer survivors are commonly used but adherence is a challenge. Few low-touch, scalable interventions exist to increase ET adherence. PURPOSE: To evaluate the acceptability, feasibility, and initial efficacy of a low-touch, remotely-delivered values plus AET education intervention (REACH) to promote AET adherence. METHODS: A mixed-methods trial randomized 88 breast cancer survivors 1:1 to REACH or Education alone. Wisepill real-time electronic adherence monitoring tracked monthly AET adherence during a 1-month baseline through 6-month follow-up (FU) (primary outcome). Patient-reported outcomes were evaluated through 3- and 6-month FU (secondary). Multiple indices of intervention feasibility and acceptability were evaluated. Qualitative exit interviews (n = 38) further assessed participants' perceptions of feasibility/acceptability and recommendations for intervention adaptation. RESULTS: The trial showed strong feasibility and acceptability, with an eligible-to-enrolled rate of 85%, 100% completion of the main intervention sessions, and "good" intervention satisfaction ratings on average. For Wisepill-assessed AET adherence, REACH outperformed Education for Month 1 of FU (p = .027) and not thereafter. Participants in REACH maintained high adherence until Month 4 of FU, whereas in Education, adherence declined significantly in Month 1. Conditions did not differ in self-reported adherence, positive affective attitudes, future intentions, or necessity beliefs. REACH trended toward less negative AET attitudes than Education at 3-month FU (p = .057) reflecting improvement in REACH (p = .004) but not Education (p = .809). Exploratory moderator analyses showed that average to highly positive baseline AET affective attitudes and oncologist-patient communication each predicted higher adherence following REACH than Education; low levels did not. Participants identified recommendations to strengthen the interventions. CONCLUSIONS: REACH, a low-touch values intervention, showed good feasibility and acceptability, and initial promise in improving objectively-assessed AET adherence among breast cancer survivors (relative to education alone). Future research should target improving REACH's tailoring and endurance.

Do all patients with cancer experience fatigue? A longitudinal study of fatigue trajectories in women with breast cancer.

BACKGROUND: Fatigue is a common and expected side effect of cancer treatment. However, the majority of studies to date have focused on average levels of fatigue, which may obscure important individual differences in the severity and course of fatigue over time. The current study was designed to identify distinct trajectories of fatigue from diagnosis into survivorship in a longitudinal study of women with early-stage breast cancer. METHODS: Women with stage 0 to stage IIIA breast cancer (270 women) were recruited before (neo)adjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy and completed assessments at baseline; posttreatment; and at 6 months, 12 months, and 18 months of follow-up. Growth mixture modeling was used to identify trajectories of fatigue, and differences among the trajectory groups with regard to demographic, medical, and psychosocial variables were examined. RESULTS: Five distinct trajectories of fatigue were identified: Stable Low (66%), with low levels of fatigue across assessments; Stable High (13%), with high fatigue across assessments; Decreasing (4%), with high fatigue at baseline that resolved over time; Increasing (9%), with low fatigue at baseline that increased over time; and Reactive (8%), with increased fatigue after treatment that resolved over time. Both psychological and treatment-related factors were found to be associated with fatigue trajectories, with psychological factors most strongly linked to high fatigue at the beginning of and over the course of treatment. CONCLUSIONS: There is considerable variability in the experience of fatigue among women with early-stage breast cancer. Although the majority of women report relatively low fatigue, those with a history of depression and elevated psychological distress may be at risk of more severe and persistent fatigue.

Vulnerability to inflammation-related depressive symptoms: Moderation by stress in women with breast cancer.

BACKGROUND: Stress precipitates depression and may do so in part by increasing susceptibility to inflammation-induced depressive symptoms. However, this has not been examined among individuals facing a major life stressor. Accordingly, the present study tested the moderating role of stress on the longitudinal association between inflammation and depressive symptoms among women with breast cancer. METHODS: Women recently diagnosed with early-stage breast cancer (N = 187) were enrolled before starting adjuvant/neoadjuvant treatment. Blood draws and self-reported depressive symptoms were collected pre-treatment, post-treatment, and at 6, 12, and 18-month post-treatment follow ups. C-reactive protein (CRP) was used to index inflammation. Measures of psychological stress, including cancer-related stress, general stress perceptions, and childhood stress, were administered pre-treatment. RESULTS: Stress moderated the association between CRP and depressive symptoms, such that higher levels of CRP were associated with elevated depressive symptoms only among women who reported high cancer-related stress (ß = 0.080, p = .002) and perceived stress (ß = 0.053, p = .044); childhood stress effects were non-significant. Moreover, elevated CRP was associated with increased odds of exhibiting clinically significant depressive symptoms (OR = 1.64, p < .001) among women who reported high cancer-related stress. Results were independent of age, BMI, race and cancer-related covariates. CONCLUSIONS: Stress was found to heighten sensitivity to inflammation-associated depressive symptoms over a 2-year period, with notably stronger effects for subjective stress responses to a concurrent life event. Individuals who are most distressed following a major life event may exhibit the greatest risk for inflammation-induced depression.

Longitudinal trajectories of adiposity-related measures from age 2-5 years in a population of low-income Hispanic children.

BACKGROUND: We estimated longitudinal trajectories of body mass index (BMI) z-score and percentile, weight for height (WFH) z-score and percentile, and percentage of the 95th BMI percentile (BMIp95) among low-income Hispanic children ages 2-5 years to provide normative data for this population and compare the behavior of different measures. METHODS: Longitudinal height and weight measurements obtained from 18,072 Hispanic children aged 2-5 years enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children in Los Angeles County were analyzed. Trajectories of adiposity-related measures were estimated using mixed models, stratified by sex and BMI percentile at age 2 years. RESULTS: For children in the 5th-85th BMI percentile at age 2 years, all adiposity-related measures rose during ages 2-3.5 years; during ages 3.5-5 years, BMI-based measures increased, BMIp95 decreased, and WFH-based measures were stable. For children exceeding the 85th BMI percentile at age 2 years, measures generally trended downward during ages 2-5 years, except for BMIp95, which had variable trends. CONCLUSIONS: Adiposity measures changed at different rates as children grew during ages 2-3.5 years compared to ages 3.5-5 years, and different measures displayed different trends. Studies should consider examining multiple measures and focusing on change relative to a comparison group. IMPACT: To address the childhood obesity epidemic, information on normative trajectories of adiposity-related measures in at-risk populations of young children is needed. Longitudinal analysis of data collected from low-income Hispanic children during ages 2-5 years revealed different patterns for different adiposity measures and for ages 2-3.5 years versus 3.5-5 years. Child obesity studies should consider examining multiple adiposity measures and focus on change relative to a comparison group to avoid misinterpreting longitudinal patterns.

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.

RESUMEN: La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Residential proximity to plant nurseries and risk of childhood leukemia.

BACKGROUND: Pesticides are a potential risk factor for childhood leukemia. Studies evaluating the role of prenatal and/or early life exposure to pesticides in the development of childhood leukemia have produced a range of results. In addition to indoor use of pesticides, higher risks have been reported for children born near agricultural crops. No studies have looked at pesticide exposure based on proximity of birth residence to commercial plant nurseries, even though nurseries are located much closer to residences than agricultural crops and can potentially result in chronic year-round pesticide exposure. OBJECTIVES: To evaluate whether risk of childhood leukemia is associated with pesticide use as determined by distance of residence at birth to commercial, outdoor plant nurseries. METHODS: We conducted a large statewide, record-based case-control study of childhood leukemia in California, which included 5788 childhood leukemia cases and an equal number of controls. Pesticide exposure was based on a spatial proximity model, which combined geographic information system data with aerial satellite imagery. RESULTS: Overall, the results supported an increased childhood leukemia risk only for birth residences very close to nurseries. For birth residences less than 75 m from plant nurseries, we found an increased risk of childhood leukemia (odds ratio (OR) 2.40, 95% confidence interval (CI) 0.99-5.82) that was stronger for acute lymphocytic leukemia (OR 3.09, 95% CI 1.14-8.34). DISCUSSION: The association was robust to choices of reference group, cut points and data quality. Our findings suggest that close proximity to plant nurseries may be a risk factor for childhood leukemia and that this relationship should be further evaluated.

The role of income and neighbourhood poverty in the association between the 2009 Special Supplemental Nutrition Program for Women, Infants and Children (WIC) food package change and child obesity among WIC-participating children in Los Angeles County, 2003-2016.

OBJECTIVE: To determine whether a previously reported association between the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) food package change and reduced child obesity risk among WIC-participating children in Los Angeles County holds across levels of family income and neighbourhood poverty. DESIGN: Analysis of prospectively collected WIC administrative data. The outcome was obesity at age 4 years (BMI-for-age ≥ 95th percentile). Poisson regression was applied to a matched sample (n 79 502) to determine if the association between the WIC food package change and child obesity was modified by family income (<50 % federal poverty level (FPL), 50-100 % FPL, >100 % but <185 % FPL) and neighbourhood poverty. SETTING: Los Angeles County, California. PARTICIPANTS: Children who participated in WIC in Los Angeles County between 2003 and 2016; children were grouped as receiving the old WIC food package (2003-2009) or the new WIC food package (2010-2016). RESULTS: Receiving the new WIC food package (i.e., post-2009) was associated with 7-18 % lower obesity risk across all family income categories. Neither family income nor neighbourhood poverty significantly modified the association between the WIC food package and child obesity. However, certain sub-groups seemed to benefit more from the food package change than others. In particular, boys from families with income above poverty but residing in the poorest neighbourhoods experienced the greatest reductions in obesity risk (relative risk = 0·77; 95 % CI 0·66, 0·88). CONCLUSIONS: The WIC food package revisions were associated with reduced childhood obesity risk among all WIC-participating families in Los Angeles County, across levels of income eligibility and neighbourhood poverty.

Engaging Latino Adolescent and Young Adult (AYA) Cancer Survivors in Their Care: Piloting a Photonovela Intervention.

Latino adolescent and young adult (AYA) cancer survivors represent a growing population given the changing demographics in the USA. They experience significant healthcare disparities and barriers that warrant age-specific and culturally appropriate interventions to improve their clinical and psychosocial outcomes. This single-arm pilot study evaluated a novel intervention - a photonovela - on its ability to educate Latino AYA survivors and their family members and engage them in survivorship care. Ninety-seven participants (Latino AYA survivors and their family members) were recruited for this study. Three surveys assessing survivorship care confidence, cancer stigma, and survivorship care knowledge were administered to families before they received the photonovela, after the intervention, and at a booster phone call session. Mixed effects models were used to evaluate differences in scores at the three time points while accounting for repeated measures and family clustering. Results show that the photonovela was effective in improving survivorship care confidence and knowledge of Latino AYA survivors and their families. This pilot study indicates that the photonovela has potential to be a useful intervention for improving confidence and knowledge regarding the need to seek survivorship care for Latino AYA cancer survivors.

Disparities in cancer mortality in Los Angeles County, 1999-2013: an analysis comparing trends in under-resourced and affluent regions.

PURPOSE: While cancer mortality has declined by 27% between 1991 and 2016 in the United States, there are large disparities in cancer mortality by racial/ethnic groups, socioeconomic status and access to care. The purpose of this analysis is to compare trends in cancer mortality among regions (Service Planning Areas, SPAs) in Los Angeles (LA) County that vary with respect to racial/ethnic distribution and social determinants of health, including poverty, education and access to care. METHODS: We estimated age- and race/ethnicity-standardized mortality for lung, colorectal (CRC) and breast cancer for eight SPAs from 1999 to 2013. We calculated three recommended measures of disparities that reflect absolute, relative and between-group disparities. RESULTS: In all of LA County, statistically significant declines in age- and race/ethnicity-standardized mortality ranged from 30% for lung cancer to 20% for CRC to 15% for breast cancer. Despite some of the largest declines in the most under-resourced SPAs (South LA, East LA, South Bay), disparities between the lowest and highest mortality by SPA did not significantly change from 1999 to 2013. CONCLUSIONS: Despite significant declines in cancer mortality in LA County from 1999 to 2013, and in racial/ethnic groups, there was little progress toward reducing disparities among SPAs. Highest mortalities for the three cancers were observed in Antelope Valley, San Fernando Valley, San Gabriel Valley, South LA and East LA. Findings demonstrate the importance of examining regional differences in cancer mortality to identify areas with highest needs for interventions and policies to reduce cancer disparities.

Childhood maltreatment and monocyte gene expression among women with breast cancer.

BACKGROUND: Childhood adversity is reliably associated with immune alterations in adulthood, including increases in inflammatory processes. However, relatively few studies have investigated these associations in clinical populations such as cancer patients who are at risk for negative immune-related health outcomes. The current study tested the hypothesis that childhood maltreatment would be associated with alterations in immune-related gene expression in monocytes from women with breast cancer. METHODS: Women (n = 86) were recruited after diagnosis with early-stage breast cancer but before onset of adjuvant therapy with radiation, chemotherapy, and/or endocrine therapy. Participants completed questionnaires to assess childhood maltreatment (Childhood Trauma Questionnaire; CTQ) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) and provided blood samples for immune assessment. CD14+ monocytes were isolated for RNA extraction and gene expression analyses. RESULTS: Based on responses to the CTQ, 28% of participants were classified as experiencing physical and/or emotional abuse or neglect and 7% as experiencing sexual abuse. Genome-wide transcriptional profiling of isolated monocytes identified 202 gene transcripts that differed in average expression level by > 25% over the range of maltreatment exposure. Bioinformatics analyses of those gene transcripts identified a significantly greater prevalence of NF-κB-binding motifs within the promoters of up-regulated vs. down-regulated genes (p = .028) in women exposed to childhood maltreatment, indicating greater inflammatory signaling. Parallel analyses of Type I interferon signaling also indicated greater prevalence of Interferon Response Factor (IRF)-related binding sites in women with a childhood maltreatment history (p = .020). Results remained significant in analyses controlling for current depression; however, NF-κB and IRF-related gene expression was higher in women with both maltreatment exposure and current depression. CONCLUSIONS: In women recently diagnosed with early-stage breast cancer, childhood maltreatment was associated with increases in the classical NF-kB-related pro-inflammatory signaling pathway and with increases in the Type I interferon system. These results suggest a broad pattern of chronic immunologic activation in breast cancer patients with a history of childhood maltreatment, particularly those who are currently experiencing clinically significant depressive symptoms. These findings have implications for the long-term health and well-being of maltreatment exposed breast cancer patients.

The new child food package is associated with reduced obesity risk among formula fed infants participating in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in Los Angeles County, California, 2003-2016.

BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) changed the food packages provided to its participants in 2009, to better align them with the Dietary Guidelines for Americans. Previous research found that the 2009 WIC food package change was associated with reduced obesity risk, particularly among breastfed infants but also among those who were never breastfed. The objective of this study was to determine if the new child food package introduced in 2009, including more produce and whole grains for 1-4-year old children, was associated with healthier growth trajectories and reduced obesity risk at age 4 years among children who were exclusively formula fed during infancy. METHODS: Administrative data on WIC-participating children in Los Angeles County, 2003-2016, were used (N = 74,871), including repeated measures of weight and length (or height); child's age, gender, and race/ethnicity; maternal education and language; and family poverty. Gender-stratified spline mixed models were used to examine weight-for-height z-score (WHZ) growth trajectories from 0 to 4 years and Poisson regression models were used to assess obesity (BMI-for-age > 95th percentile) at age 4. The main independent variable was duration of receipt (dose) of the new child package, categorized as 0, > 0 to < 1, 1 to < 2, 2 to < 3, 3 to < 4, and 4 years. RESULTS: WHZ growth trajectories were similar for children across new child package dose groups. Boys and girls who were fully formula fed during infancy but received the new child food package for 4 years had a 7% (RR = 0.93; 95%CI = 0.89-0.98) and a 6% (RR = 0.94; 95%CI = 0.89-0.99) lower obesity risk, respectively, compared to children who received the new child food package for 0 years. There were no differences in obesity risk for children receiving < 4 years of the new child package vs. 0 years. CONCLUSIONS: Providing healthy foods during childhood to children who were exclusively formula fed as infants was associated with modest improvements in obesity outcomes. While breastfeeding promotion should still be prioritized among WIC participants, providing healthy foods during childhood may provide health benefits to formula fed children, who comprise a sizeable proportion of children served by WIC.

Modeling observations with a detection limit using a truncated normal distribution with censoring.

BACKGROUND: When data are collected subject to a detection limit, observations below the detection limit may be considered censored. In addition, the domain of such observations may be restricted; for example, values may be required to be non-negative. METHODS: We propose a method for estimating population mean and variance from censored observations that accounts for known domain restriction. The method finds maximum likelihood estimates assuming an underlying truncated normal distribution. RESULTS: We show that our method, tcensReg, has lower bias, Type I error rates, and mean squared error than other methods commonly used for data with detection limits such as Tobit regression and single imputation under a range of simulation settings from mild to heavy censoring and truncation. We further demonstrate the consistency of the maximum likelihood estimators. We apply our method to analyze vision quality data collected from ophthalmology clinical trials comparing different types of intraocular lenses implanted during cataract surgery. All of the methods yield similar conclusions regarding non-inferiority, but estimates from the tcensReg method suggest that there may be greater mean differences and overall variability. CONCLUSIONS: In the presence of detection limits, our new method tcensReg provides a way to incorporate known domain restrictions in dependent variables that substantially improves inferences.