Correlates of physical activity and sedentary behavior among cancer survivors and cancer-free women: The Women's Health Accelerometry Collaboration.

BACKGROUND: Describing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population. OBJECTIVE: To describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women. METHODS: Women from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other. RESULTS: In unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB. CONCLUSION: Several sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.

Accelerometer-measured physical activity and postmenopausal breast cancer incidence in the Women's Health Accelerometry Collaboration.

BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women's Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women's Health Study [WHS]; 5714 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64-0.99), 0.84 (95% CI, 0.69-1.02), 0.89 (95% CI, 0.73-1.08), and 0.81 (95% CI, 0.64-1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than <30 kg/m2 for LPA. CONCLUSION: Greater levels of accelerometer-assessed PA were associated with lower BC risk. Associations varied by age and obesity and were not independent of BMI or physical function.

A digital health intervention to improve nutrition and physical activity in breast cancer survivors: Rationale and design of the Cook and Move for Your Life pilot and feasibility randomized controlled trial.

BACKGROUND: The design of a randomized pilot trial evaluating the feasibility of two doses of a digital health intervention promoting changes in nutrition and physical activity in breast cancer (BC) survivors is described. METHODS: Eligible women were adults with history of early-stage breast cancer and > 60 days post-treatment, consumed <5 servings/day of fruits/vegetables and/or engaged in <150 min/week of aerobic moderate-to-vigorous physical activity, and had internet access. Participants were randomized to 6 months of either a "low" (1 session) or "high" (12 sessions) dose digital health intervention. Zoom-delivered sessions focused on improving diet and physical activity through didactic and experiential classes delivered by a registered dietitian, chef, exercise physiologist, and culinary educator. All study participants received weekly motivational texts, a Fitbit, and study website access. Diet, accelerometry, anthropometric, psychosocial, and biospecimen data were collected remotely at baseline and six months. Primary outcome was feasibility measured via accrual rate, adherence, retention, and acceptability. RESULTS: Recruitment began in December 2019, was suspended in March 2020 due to the COVID-19 pandemic, resumed September 2020, and concluded in January 2021. Women were identified from the local BC registry and flyers posted in the oncology clinic. Of 929 women recruited, 321 completed the screening assessment, and of these, 138 were eligible. A total of 74 women were enrolled and randomized to the study. CONCLUSION: BC survivors were successfully enrolled in a digital health nutrition and physical activity intervention. If feasible, this intervention will be tested in larger and more diverse populations of cancer survivors. TRIAL REGISTRATION: ClinicalTrials.govNCT04200482.

Smoking Cessation Smartphone App Use Over Time: Predicting 12-Month Cessation Outcomes in a 2-Arm Randomized Trial.

BACKGROUND: Little is known about how individuals engage over time with smartphone app interventions and whether this engagement predicts health outcomes. OBJECTIVE: In the context of a randomized trial comparing 2 smartphone apps for smoking cessation, this study aimed to determine distinct groups of smartphone app log-in trajectories over a 6-month period, their association with smoking cessation outcomes at 12 months, and baseline user characteristics that predict data-driven trajectory group membership. METHODS: Functional clustering of 182 consecutive days of smoothed log-in data from both arms of a large (N=2415) randomized trial of 2 smartphone apps for smoking cessation (iCanQuit and QuitGuide) was used to identify distinct trajectory groups. Logistic regression was used to determine the association of group membership with the primary outcome of 30-day point prevalence of smoking abstinence at 12 months. Finally, the baseline characteristics associated with group membership were examined using logistic and multinomial logistic regression. The analyses were conducted separately for each app. RESULTS: For iCanQuit, participants were clustered into 3 groups: "1-week users" (610/1069, 57.06%), "4-week users" (303/1069, 28.34%), and "26-week users" (156/1069, 14.59%). For smoking cessation rates at the 12-month follow-up, compared with 1-week users, 4-week users had 50% higher odds of cessation (30% vs 23%; odds ratio [OR] 1.50, 95% CI 1.05-2.14; P=.03), whereas 26-week users had 397% higher odds (56% vs 23%; OR 4.97, 95% CI 3.31-7.52; P<.001). For QuitGuide, participants were clustered into 2 groups: "1-week users" (695/1064, 65.32%) and "3-week users" (369/1064, 34.68%). The difference in the odds of being abstinent at 12 months for 3-week users versus 1-week users was minimal (23% vs 21%; OR 1.16, 95% CI 0.84-1.62; P=.37). Different baseline characteristics predicted the trajectory group membership for each app. CONCLUSIONS: Patterns of 1-, 3-, and 4-week smartphone app use for smoking cessation may be common in how people engage in digital health interventions. There were significantly higher odds of quitting smoking among 4-week users and especially among 26-week users of the iCanQuit app. To improve study outcomes, strategies for detecting users who disengage early from these interventions (1-week users) and proactively offering them a more intensive intervention could be fruitful.

Accelerometer-Derived Daily Life Movement Classified by Machine Learning and Incidence of Cardiovascular Disease in Older Women: The OPACH Study.

Background Current physical activity guidelines focus on volume and intensity for CVD prevention rather than common behaviors responsible for movement, including those for daily living activities. We examined the associations of a machine-learned, accelerometer-measured behavior termed daily life movement (DLM) with incident CVD. Methods and Results Older women (n=5416; mean age, 79±7 years; 33% Black, 17% Hispanic) in the Women's Health Initiative OPACH (Objective Physical Activity and Cardiovascular Health) study without prior CVD wore ActiGraph GT3X+ accelerometers for up to 7 days from May 2012 to April 2014 and were followed for physician-adjudicated incident CVD through February 28th, 2020 (n=616 events). DLM was defined as standing and moving in a confined space such as performing housework or gardening. Cox models estimated hazard ratios (HR) and 95% CI, adjusting for age, race and ethnicity, education, alcohol use, smoking, multimorbidity, self-rated health, and physical function. Restricted cubic splines examined the linearity of the DLM-CVD dose-response association. We examined effect modification by age, body mass index, Reynolds Risk Score, and race and ethnicity. Adjusted HR (95% CIs) across DLM quartiles were: 1.00 (reference), 0.68 (0.55-0.84), 0.70 (0.56-0.87), and 0.57 (0.45-0.74); p-trend<0.001. The HR (95% CI) for each 1-hour increment in DLM was 0.86 (0.80-0.92) with evidence of a linear dose-response association (p non-linear>0.09). There was no evidence of effect modification by age, body mass index, Reynolds Risk Score, or race and ethnicity. Conclusions Higher DLM was independently associated with a lower risk of CVD in older women. Describing the beneficial associations of physical activity in terms of common behaviors could help older adults accumulate physical activity.

Cohort profile: the Women's Health Accelerometry Collaboration.

PURPOSE: This paper describes the Women's Health Accelerometry Collaboration, a consortium of two prospective cohort studies of women age 62 years or older, harmonised to explore the association of accelerometer-assessed physical activity and sedentary behaviour with cancer incidence and mortality. PARTICIPANTS: A total of 23 443 women (age mean 73.4, SD 6.8) living in the USA and participating in an observational study were included; 17 061 from the Women's Health Study (WHS) and 6382 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health (WHI/OPACH) Study. FINDINGS TO DATE: Accelerometry, cancer outcomes and covariate harmonisation was conducted to align the two cohort studies. Physical activity and sedentary behaviour were measured using similar procedures with an ActiGraph GT3X+ accelerometer, worn at the hip for 1 week, during 2011-2014 for WHS and 2012-2014 for WHI/OPACH. Cancer outcomes were ascertained via ongoing surveillance using physician adjudicated cancer diagnosis. Relevant covariates were measured using questionnaire or physical assessments. Among 23 443 women who wore the accelerometer for at least 10 hours on a single day, 22 868 women wore the accelerometer at least 10 hours/day on ≥4 of 7 days. The analytical sample (n=22 852) averaged 4976 (SD 2669) steps/day and engaged in an average of 80.8 (SD 46.5) min/day of moderate-to-vigorous, 105.5 (SD 33.3) min/day of light high and 182.1 (SD 46.1) min/day of light low physical activity. A mean of 8.7 (SD 1.7) hours/day were spent in sedentary behaviour. Overall, 11.8% of the cohort had a cancer diagnosis (other than non-melanoma skin cancer) at the time of accelerometry measurement. During an average of 5.9 (SD 1.6) years of follow-up, 1378 cancer events among which 414 were fatal have occurred. FUTURE PLANS: Using the harmonised cohort, we will access ongoing cancer surveillance to quantify the associations of physical activity and sedentary behaviour with cancer incidence and mortality.

The short physical performance battery and incident heart failure among older women: the OPACH study.

OBJECTIVE: Reduced functional capacity is a hallmark of early pre-clinical stages of heart failure (HF). The Short Physical Performance Battery (SPPB) is a valid measure of lower extremity physical function, has relatively low implementation burden, and is associated with cardiovascular disease and mortality. However, the SPPB-HF association is understudied in older women among whom HF burden is high. METHODS: Women (n = 5325; mean age 79 ± 7 years; 34% Black, 18% Hispanic, and 49% White) without prior HF completed the SPPB consisting of standing balance, strength, and walking tests that were summarized as a composite score from 0 (lowest) to 12 (highest), categorized as very low (0-3), low (4-6), medium (7-9), or high (10-12). Participants were followed for up to 8 years for incident HF (306 cases identified). Cox proportional hazards regression estimated hazard ratios (HR) adjusting for age, race/ethnicity, education, smoking, alcohol, diabetes, hypertension, COPD, osteoarthritis, depression, BMI, systolic blood pressure, lipids, glucose, and accelerometer-measured moderate-vigorous physical activity (MVPA) and sedentary time. RESULTS: Incident HF cases (crude rate per 1000 person-years) in the four SPPB categories (very low to high) were 34 (26.0), 79 (14.5), 128 (9.3), and 65 (5.6). Corresponding multivariable-adjusted HRs (95% CIs) were 2.22 (1.34-3.66), 1.63 (1.11-2.38), 1.39 (1.00-1.94), and 1.00 (referent; P-trend<0.001). Higher HF risk was associated with lower SPPB in women with major modifiable HF risk factors including obesity (HR per 3-unit SPPB decrement: present HR = 1.41, absent HR = 1.41), hypertension (present HR = 1.45, absent HR = 1.30), diabetes (present HR = 1.32, absent HR = 1.44), and lower accelerometer-measured MVPA (<45 min/day HR = 1.29, ≥45 min/day HR = 1.60); all P-interaction>0.10. CONCLUSION: Lower SPPB scores were associated with greater risk of incident HF in older women even after accounting for differences in HF risk factors and objectively measured PA. Implementing the SPPB in clinical settings could potentially enhance individual-level HF risk assessment, which should be further explored.

Risk of metabolic syndrome and metabolic phenotypes in relation to biomarker-calibrated estimates of energy and protein intakes: an investigation from the Women's Health Initiative.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures. OBJECTIVES: To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes. METHODS: Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity. RESULTS: For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15-1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00-1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02-1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95-1.03). No differences were seen when examining metabolic phenotypes. CONCLUSIONS: We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.

Feasibility of a behavioral intervention using mobile health applications to reduce cardiovascular risk factors in cancer survivors: a pilot randomized controlled trial.

PURPOSE: Determine the feasibility of a remotely delivered mobile health (mHealth)-supported intervention to improve diet and physical activity in hematologic malignancy survivors. METHODS: Pilot randomized controlled trial of a 16-week intervention for improving diet and physical activity: individualized goal-setting (daily steps, sodium, saturated fat, added sugar intake) per feedback from mHealth trackers (Fitbit for activity; Healthwatch360 for diet), supplemented by a Facebook peer support group. Controls accessed the trackers without goal-setting or peer support. Everyone received standardized survivorship counseling with tailored advice from a clinician. Actigraphy and food frequency questionnaires assessed activity and diet at baseline and follow-up. RESULTS: Forty-one participants (51.2% male; median age 45.1 years; 7.0 years from treatment) were randomized (24 intervention; 17 control). Fitbit and Healthwatch360 use were more common among intervention versus control participants (75.0% versus 70.6% and 50.0% versus 17.7% of eligible days, respectively). Most intervention participants (66.7%) engaged with Facebook; overall, 91.7% interacted with the study's mHealth applications. While no comparisons in activity or dietary outcomes between intervention versus control group met statistical significance, the intervention was associated with greater reductions in the targeted dietary factors and improvements in Healthy Eating Index-2015 score, moderate-vigorous physical activity time, and daily steps. Participant retention at 6 months was 90.2%. CONCLUSIONS: An intervention for cardiovascular risk reduction based on individualized goal-setting enhanced by mHealth and social media peer support was feasible and acceptable among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Effective and easily disseminated strategies that improve diet and physical activity in this population are needed. TRIAL REGISTRATION: Registered in ClinicalTrials.gov (NCT03574012) on June 29, 2018.

Neuropsychological and socioeconomic outcomes in adult survivors of pediatric low-grade glioma.

BACKGROUND: Current estimates suggest that 75% of children diagnosed with a central nervous system (CNS) tumor will become 5-year survivors. However, survivors of childhood CNS tumors are at increased risk for long-term morbidity. METHODS: To determine long-term neuropsychological and socioeconomic status (SES) outcomes, adult survivors of pediatric low-grade gliomas (n = 181) in the Childhood Cancer Survivor Study and a sibling comparison group that was frequency-matched by age and sex (n = 105) completed a comprehensive battery of standardized neuropsychological tests and an SES assessment. Multivariable regression models compared treatment-specific groups for neuropsychological and SES outcomes and evaluated associations with tumor location, age at diagnosis, sex, and age at evaluation. RESULTS: In adjusted models, survivors treated with surgery and radiotherapy (surgery+RT; median age at diagnosis, 7 years; median age at assessment, 41 years) scored lower on estimated IQ than survivors treated with surgery only, who scored lower than siblings (surgery+RT, 93.9; surgery only, 101.2; siblings, 108.5; all P values <.0001). Survivors diagnosed at younger ages had low scores for all outcomes (P < .05) except for attention/processing speed. For SES outcomes, survivors treated with surgery+RT had lower occupation scores (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-5.9), lower income (OR, 2.6; 95% CI, 1.3-5.0), and less education (OR, 2.1; 95% CI, 1.1-4.0) than those treated with surgery only. CONCLUSIONS: Decades after treatment, survivors treated with radiotherapy and at younger ages had poorer neuropsychological and SES outcomes. Lifelong surveillance of survivors of pediatric low-grade gliomas may be warranted as life events, stages, and transitions (employment, family, and aging) present new challenges and risks.

Association of Light Physical Activity Measured by Accelerometry and Incidence of Coronary Heart Disease and Cardiovascular Disease in Older Women.

Importance: To our knowledge, no studies have examined light physical activity (PA) measured by accelerometry and heart disease in older women. Objective: To investigate whether higher levels of light PA were associated with reduced risks of coronary heart disease (CHD) or cardiovascular disease (CVD) in older women. Design, Setting, and Participants: Prospective cohort study of older women from baseline (March 2012 to April 2014) through February 28, 2017, for up to 4.91 years. The setting was community-dwelling participants from the Women's Health Initiative. Participants were ambulatory women with no history of myocardial infarction or stroke. Exposures: Data from accelerometers worn for a requested 7 days were used to measure light PA. Main Outcomes and Measures: Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% CIs for physician-adjudicated CHD and CVD events across light PA quartiles adjusting for possible confounders. Light PA was also analyzed as a continuous variable with and without adjustment for moderate to vigorous PA (MVPA). Results: Among 5861 women (mean [SD] age, 78.5 [6.7] years), 143 CHD events and 570 CVD events were observed. The HRs for CHD in the highest vs lowest quartiles of light PA were 0.42 (95% CI, 0.25-0.70; P for trend <.001) adjusted for age and race/ethnicity and 0.58 (95% CI, 0.34-0.99; P for trend = .004) after additional adjustment for education, current smoking, alcohol consumption, physical functioning, comorbidity, and self-rated health. Corresponding HRs for CVD in the highest vs lowest quartiles of light PA were 0.63 (95% CI, 0.49-0.81; P for trend <.001) and 0.78 (95% CI, 0.60-1.00; P for trend = .004). The HRs for a 1-hour/day increment in light PA after additional adjustment for MVPA were 0.86 (95% CI, 0.73-1.00; P for trend = .05) for CHD and 0.92 (95% CI, 0.85-0.99; P for trend = .03) for CVD. Conclusions and Relevance: The present findings support the conclusion that all movement counts for the prevention of CHD and CVD in older women. Large, pragmatic randomized trials are needed to test whether increasing light PA among older women reduces cardiovascular risk.

A Mixed-Effects Model for Powerful Association Tests in Integrative Functional Genomics.

Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and shown promise for discovering novel variants. One such approach, PrediXcan, is to use predicted gene expression through genetic regulation. However, there are limitations in this approach. The predicted gene expression may be biased, resulting from regularized regression applied to moderately sample-sized reference studies. Further, some variants can individually influence disease risk through alternative functional mechanisms besides expression. Thus, testing only the association of predicted gene expression as proposed in PrediXcan will potentially lose power. To tackle these challenges, we consider a unified mixed effects model that formulates the association of intermediate phenotypes such as imputed gene expression through fixed effects, while allowing residual effects of individual variants to be random. We consider a set-based score testing framework, MiST (mixed effects score test), and propose two data-driven combination approaches to jointly test for the fixed and random effects. We establish the asymptotic distributions, which enable rapid calculation of p values for genome-wide analyses, and provide p values for fixed and random effects separately to enhance interpretability over GWASs. Extensive simulations demonstrate that our approaches are more powerful than existing ones. We apply our approach to a large-scale GWAS of colorectal cancer and identify two genes, POU5F1B and ATF1, which would have otherwise been missed by PrediXcan, after adjusting for all known loci.

Trajectories of 12-Month Usage Patterns for Two Smoking Cessation Websites: Exploring How Users Engage Over Time.

BACKGROUND: Little is known about how individuals engage with electronic health (eHealth) interventions over time and whether this engagement predicts health outcomes. OBJECTIVE: The objectives of this study, by using the example of a specific type of eHealth intervention (ie, websites for smoking cessation), were to determine (1) distinct groups of log-in trajectories over a 12-month period, (2) their association with smoking cessation, and (3) baseline user characteristics that predict trajectory group membership. METHODS: We conducted a functional clustering analysis of 365 consecutive days of log-in data from both arms of a large (N=2637) randomized trial of 2 website interventions for smoking cessation (WebQuit and Smokefree), with a primary outcome of 30-day point prevalence smoking abstinence at 12 months. We conducted analyses for each website separately. RESULTS: A total of 3 distinct trajectory groups emerged for each website. For WebQuit, participants were clustered into 3 groups: 1-week users (682/1240, 55.00% of the sample), 5-week users (399/1240, 32.18%), and 52-week users (159/1240, 12.82%). Compared with the 1-week users, the 5- and 52-week users had 57% higher odds (odds ratio [OR] 1.57, 95% CI 1.13-2.17; P=.007) and 124% higher odds (OR 2.24, 95% CI 1.45-3.43; P<.001), respectively, of being abstinent at 12 months. Smokefree users were clustered into 3 groups: 1-week users (645/1309, 49.27% of the sample), 4-week users (395/1309, 30.18%), and 5-week users (269/1309, 20.55%). Compared with the 1-week users, 5-week users (but not 4-week users; P=.99) had 48% higher odds (OR 1.48, 95% CI 1.05-2.07; P=.02) of being abstinent at 12 months. In general, the WebQuit intervention had a greater number of weekly log-ins within each of the 3 trajectory groups as compared with those of the Smokefree intervention. Baseline characteristics associated with trajectory group membership varied between websites. CONCLUSIONS: Patterns of 1-, 4-, and 5-week usage of websites may be common for how people engage in eHealth interventions. The 5-week usage of either website, and 52-week usage only of WebQuit, predicted a higher odds of quitting smoking. Strategies to increase eHealth intervention engagement for 4 more weeks (ie, from 1 week to 5 weeks) could be highly cost effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT01812278; https://www.clinicaltrials.gov/ct2/show/NCT01812278 (Archived by WebCite at http://www.webcitation.org/6yPO2OIKR).

Accelerometer-Measured Physical Activity and Mortality in Women Aged 63 to 99.

OBJECTIVES: To prospectively examine associations between accelerometer-measured physical activity (PA) and mortality in older women, with an emphasis on light-intensity PA. DESIGN: Prospective cohort study with baseline data collection between March 2012 and April 2014. SETTING: Women's Health Initiative cohort in the United States. PARTICIPANTS: Community-dwelling women aged 63 to 99 (N = 6,382). MEASUREMENTS: Minutes per day of usual PA measured using hip-worn triaxial accelerometers, physical functioning measured using the Short Physical Performance Battery, mortality follow-up for a mean 3.1 years through September 2016 (450 deaths). RESULTS: When adjusted for accelerometer wear time, age, race-ethnicity, education, smoking, alcohol, self-rated health, and comorbidities, relative risks (95% confidence intervals) for all-cause mortality across PA tertiles were 1.00 (referent), 0.86 (0.69, 1.08), 0.80 (0.62, 1.03) trend P = .07, for low light; 1.00, 0.57 (0.45, 0.71), 0.47 (0.35, 0.61) trend P < .001, for high light; and, 1.00, 0.63 (0.50, 0.79), 0.42 (0.30, 0.57) trend P < .001, for moderate-to-vigorous PA (MVPA). Associations remained significant for high light-intensity PA and MVPA (P < .001) after further adjustment for physical function. Each 30-min/d increment in light-intensity (low and high combined) PA and MVPA was associated, on average, with multivariable relative risk reductions of 12% and 39%, respectively (P < .01). After further simultaneous adjusting for light intensity and MVPA, the inverse associations remained significant (light-intensity PA: RR = 0.93, 95% CI = 0.89-0.97; MVPA: RR = 0.67, 95% CI = 0.58-0.78). These relative risks did not differ between subgroups for age or race and ethnicity (interaction, P ≥ .14, all). CONCLUSION: When measured using accelerometers, light-intensity and MVPA are associated with lower mortality in older women. These findings suggest that replacing sedentary time with light-intensity PA is a public health strategy that could benefit an aging society and warrants further investigation.

Leisure-time physical activity and leukocyte telomere length among older women.

BACKGROUND: Shortened leukocyte telomere length (LTL), a purported marker of cellular aging, is associated with morbidity and mortality. However, the association of physical activity, a modifiable lifestyle behavior, with LTL has not been adequately studied among older adults. METHODS: In this cross-sectional study, we examined associations of various intensity levels of leisure-time physical activity with LTL among 1476 older white and African American women from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health study. Self-reported physical activity was assessed by questionnaire, and LTL was measured by Southern blot. The association between physical activity and LTL was evaluated using multiple linear regression models adjusted for demographic characteristics, lifestyle behaviors, and health-related variables. RESULTS: Women were on average aged 79.2 (standard deviation 6.7) years old. In the final model adjusted for age, race/ethnicity, education, marital status, smoking, alcohol, body mass index, a history of chronic diseases, and hormone therapy use, LTL was on average 110 (95% confidence interval, 20-190) base pairs longer among women in the highest (≥17.00MET-hours/week) compared with the lowest (<1.25MET-hours/week) level of total leisure-time physical activity (P for trend=0.02). Higher levels of moderate-to-vigorous physical activity (P for trend=0.04) and faster walking speed (P for trend=0.03) were also associated with longer LTL in the fully-adjusted models. CONCLUSION: Older women participating in greater amounts of total leisure-time physical activity and moderate-to-vigorous physical activity had longer LTL.

Association of Accelerometer-Measured Physical Activity With Leukocyte Telomere Length Among Older Women.

BACKGROUND: Previous studies on physical activity and telomere length have relied largely upon self-reported physical activity data, and few studies have examined older adults. The association of objectively measured physical activity with leukocyte telomere length (LTL) is currently unknown. METHODS: In this study, we examined cross-sectional associations between accelerometer-measured total, light, and moderate-to-vigorous physical activity (MVPA) and LTL, measured using Southern blot. The sample included 1,405 older (64-95 years old) white and African American women from the Women's Health Initiative. Multiple linear regression models adjusting for potential confounders were used to determine the association between accelerometer-measured physical activity and LTL. RESULTS: Overall, the mean (standard deviation) of total, light, and moderate-to-vigorous activity was 5.5 (1.6), 4.7 (1.3), and 0.8 (0.5) h/d, respectively. Adjusting for accelerometer wear time, age, race/ethnicity, education, marital status, smoking, alcohol, body mass index, a history of chronic diseases, and hormone therapy use, LTL was 80 (95% confidence interval: 9, 150) base pairs longer among women with ≥2.5 compared with <2.5 h/wk of MVPA. Light activity was not significantly associated with LTL. For total activity, the most physically active women had significantly longer LTL than the least active women after adjustment for demographic and lifestyle characteristics; however, findings were not significant after further adjustment for health-related factors. CONCLUSIONS: Older women meeting current recommendations of ≥2.5 h/wk of MVPA, as assessed by accelerometer, had longer LTL. Additional studies using accelerometers in large, diverse cohorts of older women are needed to confirm and extend these findings.

The Objective Physical Activity and Cardiovascular Disease Health in Older Women (OPACH) Study.

BACKGROUND: Limited evidence exists to inform physical activity (PA) and sedentary behavior guidelines for older people, especially women. Rigorous evidence on the amounts, intensities, and movement patterns associated with better health in later life is needed. METHODS/DESIGN: The Objective PA and Cardiovascular Health (OPACH) Study is an ancillary study to the Women's Health Initiative (WHI) Program that examines associations of accelerometer-assessed PA and sedentary behavior with cardiovascular and fall events. Between 2012 and 2014, 7048 women aged 63-99 were provided with an ActiGraph GT3X+ (Pensacola, Florida) triaxial accelerometer, a sleep log, and an OPACH PA Questionnaire; 6489 have accelerometer data. Most women were in their 70s (40%) or 80s (46%), while approximately 10% were in their 60s and 4% were age 90 years or older. Non-Hispanic Black or Hispanic/Latina women comprise half of the cohort. Follow-up includes 1-year of falls surveillance with monthly calendars and telephone interviews of fallers, and annual follow-up for outcomes with adjudication of incident cardiovascular disease (CVD) events through 2020. Over 63,600 months of calendar pages were returned by 5,776 women, who reported 5,980 falls. Telephone interviews were completed for 1,492 women to ascertain the circumstances, injuries and medical care associated with falling. The dataset contains extensive information on phenotypes related to healthy aging, including inflammatory and CVD biomarkers, breast and colon cancer, hip and other fractures, diabetes, and physical disability. DISCUSSION: This paper describes the study design, methods, and baseline data for a diverse cohort of postmenopausal women who wore accelerometers under free-living conditions as part of the OPACH Study. By using accelerometers to collect more precise and complete data on PA and sedentary behavior in a large cohort of older women, this study will contribute crucial new evidence about how much, how vigorous, and what patterns of PA are necessary to maintain optimal cardiovascular health and to avoid falls in later life. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00000611 . Registered 27 October 1999.

Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

Background: Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized. Methods: The Childhood Cancer Survivor Study (CCSS) includes 380 five-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models. Results: Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66). Conclusions: Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority.

A unified powerful set-based test for sequencing data analysis of GxE interactions.

The development of next-generation sequencing technologies has allowed researchers to study comprehensively the contribution of genetic variation particularly rare variants to complex diseases. To date many sequencing analyses of rare variants have focused on marginal genetic effects and have not explored the potential role environmental factors play in modifying genetic risk. Analysis of gene-environment interaction (GxE) for rare variants poses considerable challenges because of variant rarity and paucity of subjects who carry the variants while being exposed. To tackle this challenge, we propose a hierarchical model to jointly assess the GxE effects of a set of rare variants for example, in a gene or regulatory region, leveraging the information across the variants. Under this model, GxE is modeled by two components. The first component incorporates variant functional information as weights to calculate the weighted burden of variant alleles across variants, and then assess their GxE interaction with the environmental factor. Since this information is a priori known, this component is fixed effects in the model. The second component involves residual GxE effects that have not been accounted for by the fixed effects. In this component, the residual GxE effects are postulated to follow an unspecified distribution with mean 0 and variance [Formula: see text] We develop a novel testing procedure by deriving two independent score statistics for the fixed effects and the variance component separately. We propose two data-adaptive combination approaches for combining these two score statistics and establish the asymptotic distributions. An extensive simulation study shows that the proposed approaches maintain the correct type I error and the power is comparable to or better than existing methods under a wide range of scenarios. Finally we illustrate the proposed methods by a exome-wide GxE analysis with NSAIDs use in colorectal cancer.

Behavioral, Social, and Emotional Symptom Comorbidities and Profiles in Adolescent Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

PURPOSE: In the general population, psychological symptoms frequently co-occur; however, profiles of symptom comorbidities have not been examined among adolescent survivors of childhood cancer. PATIENTS AND METHODS: Parents of 3,893 5-year survivors of childhood cancer who were treated between 1970 and 1999 and who were assessed in adolescence (age 12 to 17 years) completed the Behavior Problems Index. Age- and sex-standardized z scores were calculated for symptom domains by using the Childhood Cancer Survivor Study sibling cohort. Latent profile analysis identified profiles of comorbid symptoms, and multivariable multinomial logistic regression modeling examined associations between cancer treatment exposures and physical late effects and identified symptom profiles. Odds ratios (ORs) and 95% CIs for latent class membership were estimated and analyses were stratified by cranial radiation therapy (CRT; CRT or no CRT). RESULTS: Four symptoms profiles were identified: no significant symptoms (CRT, 63%; no CRT, 70%); elevated anxiety and/or depression, social withdrawal, and attention problems (internalizing; CRT, 31%; no CRT, 16%); elevated headstrong behavior and attention problems (externalizing; CRT, no observed; no CRT, 9%); and elevated internalizing and externalizing symptoms (global symptoms; CRT, 6%; no CRT, 5%). Treatment with ≥ 30 Gy CRT conferred greater risk of internalizing (OR, 1.7; 95% CI, 1.0 to 2.8) and global symptoms (OR, 3.2; 95% CI, 1.2 to 8.4). Among the no CRT group, corticosteroid treatment was associated with externalizing symptoms (OR, 1.9; 95% CI, 1.2 to 2.8) and ≥ 4.3 g/m(2) intravenous methotrexate exposure was associated with global symptoms (OR, 1.5; 95% CI, 0.9 to 2.4). Treatment late effects, including obesity, cancer-related pain, and sensory impairments, were significantly associated with increased risk of comorbid symptoms. CONCLUSION: Behavioral, emotional, and social symptoms frequently co-occur in adolescent survivors of childhood cancer and are associated with treatment exposures and physical late effects. Assessment and consideration of symptom profiles are essential for directing appropriate mental health treatment for adolescent survivors.