Interpretation of coefficients in segmented regression for interrupted time series analyses.

Background: Segmented regression, a common model for interrupted time series (ITS) analysis, primarily utilizes two equation parametrizations. Interpretations of coefficients vary between the two segmented regression parametrizations, leading to occasional user misinterpretations. Methods: To illustrate differences in coefficient interpretation between two common parametrizations of segmented regression in ITS analysis, we derived analytical results and present an illustration evaluating the impact of a smoking regulation policy in Italy using a publicly accessible dataset. Estimated coefficients and their standard errors were obtained using two commonly used parametrizations for segmented regression with continuous outcomes. We clarified coefficient interpretations and intervention effect calculations. Results: Our investigation revealed that both parametrizations represent the same model. However, due to differences in parametrization, the immediate effect of the intervention is estimated differently under the two approaches. The key difference lies in the interpretation of the coefficient related to the binary indicator for intervention implementation, impacting the calculation of the immediate effect. Conclusions: Two common parametrizations of segmented regression represent the same model but have different interpretations of a key coefficient. Researchers employing either parametrization should exercise caution when interpreting coefficients and calculating intervention effects.

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.

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.

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.

Investigating the relationship between participation in the building infrastructure leading to diversity (BUILD) initiative and intent to pursue a science career: A cross-sectional analysis.

This paper presents an analysis of survey data to examine the association between supervised structured mentoring and students' intent to pursue a career in science. Data were collected from students in the 10 Building Infrastructure Leading to Diversity (BUILD) research training programs, developed through grants from the National Institutes of Health. Propensity score matching and multinomial logistic regression demonstrated that exposure to BUILD programs-meaning participation in undergraduate research, receipt of mentoring from a primary mentor, and/or participation as a funded scholar and/or associate of each BUILD site's training program-was associated with increased intent to pursue a science career. These findings have implications for STEM program evaluation and practice in higher education.

A semi-Markov multistate cure model for estimating intervention effects in stepped wedge design trials.

Multistate models are useful for studying exposures that affect transitions among a set of health states. However, they can be challenging to apply when exposures are time-varying. We develop a multistate model and a method of likelihood construction that allows application of the model to data in which interventions or other exposures can be time-varying and an individual may to be exposed to multiple intervention conditions while progressing through states. The model includes cure proportions, reflecting the possibility that some individuals will never leave certain states. We apply the approach to analyze patient vaccination data from a stepped wedge design trial evaluating two interventions to increase uptake of human papillomavirus vaccination. The states are defined as the number of vaccine doses the patient has received. We model state transitions as a semi-Markov process and include cure proportions to account for individuals who will never leave a given state (e.g. never receive their next dose). Multistate models typically quantify intervention effects as hazard ratios contrasting the intensities of transitions between states in intervention versus control conditions. For multistate processes, another clinically meaningful outcome is the change in the percentage of the study population that has achieved a specific state (e.g. completion of all required doses) by a specific point in time due to an intervention. We present a method for quantifying intervention effects in this manner. We apply the model to both simulated and real-world data and also explore some conditions under which such models may give biased results.

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.

Improving biobehavioral health in younger breast cancer survivors: Pathways to Wellness trial secondary outcomes.

BACKGROUND: The Pathways to Wellness trial tested the efficacy of 2 interventions for younger breast cancer survivors: mindful awareness practices (MAPs) and survivorship education (SE). This planned secondary analysis examines intervention effects on stress, positive psychological outcomes, and inflammation (Clincaltrials.gov NCT03025139). METHODS: Women diagnosed with breast cancer at or before age 50 years who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments conducted at pre- and postintervention and at 3- and 6-month follow-up measured general stress perceptions, cancer-related intrusive thoughts and worry, positive affect, meaning and peace in life, altruism and empathy, and markers of inflammation. Analyses compared change in outcomes over time in each intervention group relative to WLC using linear mixed models. RESULTS: A total 247 women were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs statistically significantly decreased intrusive thoughts and worry at postintervention and 3-month follow-up relative to WLC (P < .027) and statistically significantly increased positive affect and meaning and peace at postintervention, with positive affect persisting at 3-month follow-up (P < .027). SE statistically significantly decreased intrusive thoughts at 3-month follow-up and statistically significantly increased positive affect at 6-month follow-up relative to WLC (P < .01). Proinflammatory gene expression increased in WLC relative to MAPs (P = .016) but did not differ from SE. There were no intervention effects on other outcomes. CONCLUSION: MAPs had beneficial effects on psychological and immune outcomes in younger breast cancer survivors and is a promising approach for enhancing biobehavioral health.

Cluster-randomized trials of cancer screening interventions: Has use of appropriate statistical methods increased over time?

BACKGROUND: In a cluster randomized trial, groups of individuals (e.g., clinics, schools) are randomized to conditions. The design and analysis of cluster randomized trials can require more care than individually randomized trials. Past reviews have noted deficiencies in the use of appropriate statistical methods for such trials. METHODS: We reviewed cluster randomized trials of cancer screening interventions published 1995-2019 to determine whether appropriate statistical methods had been used for sample size calculation and outcome analysis and whether they reported intraclass correlation coefficient (ICC) values. This work expanded a previous review of articles published 1995-2010. RESULTS: Our search identified 88 articles published 1995-2020 that reported outcomes of cluster randomized trials of breast, cervix, and colorectal cancer screening interventions. There was increased reporting of the trials' sample size calculations over time, with the percentage increasing from 31% in 1995-2004 to 77% in 2014-2019. However, the percentage of calculations failing to account for cluster randomization did not change over time and was 17% of studies in 2014-2019. There was a nonsignificant trend towards increased use of outcome analysis methods that accounted for the cluster randomized design. However, in lower impact journals, use of appropriate analysis methods was only 80% in 2014-2019. Only 33% of studies reported ICC values in 2014-2019. CONCLUSION: For cluster randomized trials with cancer screening outcomes, there have been improvements in the reporting of sample size calculations but methodological and reporting deficiencies persist. Efforts to disseminate, adopt and report the use of appropriate statistical methodologies are still needed.

Health selection on self-rated health and the healthy migrant effect: Baseline and 1-year results from the health of Philippine Emigrants Study.

Studies of migration and health focus on a "healthy migrant effect" whereby migrants are healthier than individuals not migrating. Health selection remains the popular explanation of this phenomenon. However, studies are mixed on whether selection occurs and typically examine migrants post-departure. This study used a novel pre-migration dataset to identify which health and social domains differ between migrants and their non-migrant counterparts and their contribution to explaining variance in self-rated health by migrant status at pre-migration and 1-year later. Data were used from the baseline and 1-year follow-up of the Health of Philippine Emigrants Study (HoPES). We used multivariable ordinary least squares regression to examine differences in self-rated health between migrants to the U.S. and a comparable group of non-migrants at baseline (premigration) and one year later, accounting for seven domains: physical health, mental health, health behavior, demographics, socioeconomic factors and healthcare utilization, psychosocial factors, and social desirability. A migrant advantage was present for self-rated health at baseline and 1-year. Accounting for all domains, migrants reported better self-rated health compared to non-migrants both at baseline (ß = 0.32; 95% CI = 0.22, 0.43) and at 1-year (ß = 0.28; 95% CI = 0.10, 0.46). Migrant status, health behavior, and mental health accounted for most of the variance in self-rated health both at baseline and 1-year follow-up. This analysis provides evidence of migrant health selection and nuanced understanding to what is being captured by self-rated health in studies of migrant health that should be considered in future research.

Acute health-related quality of life outcomes and systemic inflammatory markers following contemporary breast cancer surgery.

Contemporary breast cancer surgical procedures vary greatly by the amount of tissue removed, anesthesia time, and reconstruction. Despite historical literature comparing the health-related quality of life (HRQOL) after lumpectomy and mastectomy, HRQOL data are limited regarding contemporary surgical procedures. Further, biological processes (e.g., inflammation) associated with HRQOL outcomes have not been described. We conducted two studies to examine differences in post-operative physical and mental functioning, pain, fatigue, and systemic inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) in women with early-stage breast cancer. Study 1 assessed women before and after surgery (n = 27) and Study 2 used a large cross-sectional sample (n = 240) to confirm findings from Study 1 and included a no-surgery comparison group. In Study 1, women who received mastectomy had lower physical functioning than lumpectomy (ps < 0.05), and those who received bilateral mastectomy had worse pain (p < 0.01) and fatigue (p = 0.029) than lumpectomy. Results were replicated in Study 2: mastectomy groups exhibited poorer physical functioning (ps < 0.01) and greater pain (ps < 0.001) than lumpectomy, and bilateral mastectomy was associated with worse fatigue (p < 0.05). Women who received bilateral mastectomy had higher levels of CRP than lumpectomy (p < 0.01) and higher TNF-α than the no-surgery group (p < 0.05). All surgery groups exhibited higher IL-6 than no-surgery (ps < 0.05). More extensive surgery is associated with poorer postoperative HRQOL. As compared to lumpectomy and no-surgery, mastectomy is associated with higher concentrations of systemic inflammatory markers.

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.

Impact of a Multi-Level, Multi-Component, System Intervention on HPV Vaccination in a Federally Qualified Health Center.

BACKGROUND: Human papillomavirus (HPV) vaccines can significantly reduce the burden of HPV-associated cancers, but remain underutilized. We evaluated a multi-component, system-level intervention to improve HPV vaccination in a large Federally Qualified Health Center (FQHC) that serves a primarily low income Latino population. METHODS: From January 2015 through March 2017, we evaluated the effectiveness of a multi-component, system-level intervention to improve HPV vaccination rates in eight clinics randomly assigned to study condition (four intervention, four usual care). The intervention included parent reminders for HPV vaccine series completion, provider training, clinic-level audit and feedback, and workflow modifications to reduce missed opportunities for vaccination. Using a difference-in-differences approach, we compared HPV vaccination rates among patients, ages 11 to 17 during a 12-month preintervention period and a 15-month intervention period. Linear mixed models were used to estimate intervention effects on vaccine initiation and completion. RESULTS: The sample included approximately 15,000 adolescents each quarter (range 14,773-15,571; mean age 14 years; 51% female, 88% Latino). A significantly greater quarterly increase in HPV vaccine initiation was observed for intervention compared with usual care clinics (0.75 percentage point greater increase, P < 0.001), corresponding to 114 additional adolescents vaccinated per quarter. The intervention led to a greater increase in HPV vaccine completion rates among boys (0.65 percentage point greater increase, P < 0.001), but not girls. CONCLUSIONS: Our system-level intervention was associated with modest improvements in HPV vaccine initiation overall and completion among boys. IMPACT: Study findings have implications for reducing HPV-related cancers in safety net populations.

Acute and Chronic Effects of Adjuvant Therapy on Inflammatory Markers in Breast Cancer Patients.

BACKGROUND: Inflammation contributes to poor behavioral, functional, and clinical outcomes in cancer survivors. We examined whether standard cancer treatments-radiation and chemotherapy-led to acute and persistent changes in circulating markers of inflammation in breast cancer patients. METHODS: A total of 192 women diagnosed with early stage breast cancer provided blood samples before and after completion of radiation and/or chemotherapy and at 6-, 12-, and 18-month posttreatment follow-ups. Samples were assayed for circulating inflammatory markers, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, downstream markers of their activity (soluble TNF receptor type II [sTNF-RII], C reactive protein), and other inflammatory mediators (IL-8, interferon-γ [IFN-γ]). Analyses evaluated within-group changes in inflammatory markers in 4 treatment groups: no radiation or chemotherapy (n = 39), radiation only (n = 77), chemotherapy only (n = 18), and chemotherapy with radiation (n = 58). RESULTS: Patients treated with chemotherapy showed statistically significant increases in circulating concentrations of TNF-α, sTNF-RII, IL-6, and IFN-γ from pre- to posttreatment, with parameter estimates in standard deviation units ranging from 0.55 to 1.20. Those who received chemotherapy with radiation also showed statistically significant increases in IL-8 over this period. Statistically significant increases in TNF-α, sTNF-RII, IL-6, IFN-γ, and IL-8 persisted at 6, 12, and 18 months posttreatment among patients treated with chemotherapy and radiation (all P < .05). Patients treated with radiation only showed a statistically significant increase in IL-8 at 18 months posttreatment; no increases in any markers were observed in patients treated with surgery only. CONCLUSIONS: Chemotherapy is associated with acute increases in systemic inflammation that persist for months after treatment completion in patients who also receive radiation therapy. These increases may contribute to common behavioral symptoms and other comorbidities in cancer survivors.

Evaluating the impact of community interventions on childhood obesity in populations living in low-income households in Los Angeles: A simulation study.

BACKGROUND: The complex multifactorial nature of childhood obesity makes community interventions difficult to evaluate using traditional approaches; innovative methods are needed. OBJECTIVE: To evaluate the impact of various interventions targeting childhood obesity-related behaviours, and classified as using a micro-level (e.g., home visitation programs) or macro-level (e.g., business practices) strategy, on obesity among children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: We simulated a population of 1500 children enrolled in WIC, with specific diet, physical activity, breastfeeding behaviours and body mass index z-scores (BMIz), following them from age 2 to 5 years. RESULTS: Combined interventions targeting breastfeeding appeared to be moderately effective, reducing BMIz by 0.03 (95% CI -005, -0.01). Two strategy-specific interventions, home visitation programs and business practices targeting obesity-related behaviours, appeared to be moderately effective at reducing BMIz by 0.04 (95% CI -0.06, -0.02) and 0.02 (95% CI -0.04, 0.00), respectively. Contrary to expectation, combining all micro and macro interventions appeared to have no impact or moderately increased the proportion of obesity/overweight among children. CONCLUSION: Interventions targeting breastfeeding behaviour were most effective when both micro and macro strategies were implemented. Interventions targeting obesity-related behaviours in general were effective for two strategies, home visitation and business practices.

Younger women are more susceptible to inflammation: A longitudinal examination of the role of aging in inflammation and depressive symptoms.

BACKGROUND: The degree to which effects of inflammation on mood and behavior vary across the lifespan remains relatively unexplored despite well-established, age-related alterations in both the immune and central nervous systems. Further, the implications of this developmental process within different symptom domains warrants careful consideration. METHODS: Women diagnosed with breast cancer (n = 188; ages 27-89) provided blood samples and reported depressive symptoms prior to adjuvant treatment, at the end of adjuvant treatment, and 6-, 12-, and 18-months after completing adjuvant treatment via the CES-D. Blood was assayed for C-reactive Protein (CRP) and interleukin (IL)-6. We used mixed linear effect models to estimate within- and between-person effects of CRP or IL-6 on 4 domains of depressive symptoms: depressed affect, low positive affect, somatic complaints, and interpersonal problems. RESULTS: High average inflammation was associated with elevated somatic complaints (CRP p = .009, IL-6: p = .05), interpersonal problems (CRP p = .002, IL-6 p < .001), and positive affect (IL-6 p = .03), but only among the youngest women in the sample (age 50 or younger). Younger women also reported more depressed affect at assessments when inflammation was higher (CRP p = .045, IL-6 p = .09). CONCLUSIONS: The association between inflammation and specific depressive symptoms is dynamic and varies across the lifespan, which may help clarify apparent inconsistencies in the extant literature as well as inform more precise interventions targeting this pathway.

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.

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.

A meta-analysis approach for evaluating the effectiveness of complex multisite programs.

The National Institutes of Health (NIH) created the Building Infrastructure Leading to Diversity (BUILD) initiative to incentivize undergraduate institutions to create innovative approaches to increasing diversity in biomedical research, with the ultimate goal of diversifying the NIH-funded research enterprise. Initiatives such as BUILD involve designing and implementing programs at multiple sites that share common objectives. Evaluation of initiatives like this often includes statistical analyses that combine data across sites to estimate the program's impact on particular outcomes. Meta-analysis is a statistical technique for combining effect estimates from different studies to obtain a single overall effect estimate and to estimate heterogeneity across studies. However, it has not been commonly applied to evaluate the impact of a program across multiple different sites. In this chapter, we use the BUILD Scholar program-one component of the broader initiative-to demonstrate the application of meta-analysis to combine effect estimates from different sites of a multisite initiative. We analyze three student outcomes using a typical "single-stage" modeling approach and a meta-analysis approach. We show how a meta-analysis approach can provide more nuanced information about program impacts on student outcomes and thus can help support a robust evaluation.