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BACKGROUND: Sedentary behavior (SB) is a recognized risk factor for many chronic diseases. ActiGraph and activPAL are two commonly used wearable accelerometers in SB research. The former measures body movement and the latter measures body posture. The goal of the current study is to quantify the pattern and variation of movement (by ActiGraph activity counts) during activPAL-identified sitting events, and examine associations between patterns and health-related outcomes, such as systolic and diastolic blood pressure (SBP and DBP). METHODS: The current study included 314 overweight postmenopausal women, who were instructed to wear an activPAL (at thigh) and ActiGraph (at waist) simultaneously for 24 hours a day for a week under free-living conditions. ActiGraph and activPAL data were processed to obtain minute-level time-series outputs. Multilevel functional principal component analysis (MFPCA) was applied to minute-level ActiGraph activity counts within activPAL-identified sitting bouts to investigate variation in movement while sitting across subjects and days. The multilevel approach accounted for the nesting of days within subjects. RESULTS: At least 90% of the overall variation of activity counts was explained by two subject-level principal components (PC) and six day-level PCs, hence dramatically reducing the dimensions from the original minute-level scale. The first subject-level PC captured patterns of fluctuation in movement during sitting, whereas the second subject-level PC delineated variation in movement during different lengths of sitting bouts: shorter (< 30 minutes), medium (30 -39 minutes) or longer (> 39 minute). The first subject-level PC scores showed positive association with DBP (standardized ß ^ : 2.041, standard error: 0.607, adjusted p = 0.007), which implied that lower activity counts (during sitting) were associated with higher DBP. CONCLUSION: In this work we implemented MFPCA to identify variation in movement patterns during sitting bouts, and showed that these patterns were associated with cardiovascular health. Unlike existing methods, MFPCA does not require pre-specified cut-points to define activity intensity, and thus offers a novel powerful statistical tool to elucidate variation in SB patterns and health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03473145; Registered 22 March 2018; https://clinicaltrials.gov/ct2/show/NCT03473145 ; International Registered Report Identifier (IRRID): DERR1-10.2196/28684.
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Análisis de Componente Principal , Conducta Sedentaria , Sedestación , Dispositivos Electrónicos Vestibles , Anciano , Femenino , Humanos , Persona de Mediana Edad , Acelerometría/instrumentación , Acelerometría/métodos , Actigrafía/instrumentación , Actigrafía/métodos , Presión Sanguínea/fisiología , Ejercicio Físico/fisiología , Movimiento , Sobrepeso , Posmenopausia/fisiologíaRESUMEN
OBJECTIVE: Accumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers. METHODS: This study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011-2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer. RESULTS: On average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day. CONCLUSIONS: Among women 62-97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations.
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Acelerometría , Neoplasias , Salud de la Mujer , Humanos , Femenino , Anciano , Neoplasias/epidemiología , Neoplasias/mortalidad , Persona de Mediana Edad , Ejercicio Físico , Factores de Riesgo , Estudios de Cohortes , Caminata , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
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.
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Neoplasias de la Mama , Femenino , Humanos , Anciano , Neoplasias de la Mama/epidemiología , Incidencia , Posmenopausia , Ejercicio Físico , Salud de la Mujer , AcelerometríaRESUMEN
Functional principal component analysis (FPCA) has been widely used to capture major modes of variation and reduce dimensions in functional data analysis. However, standard FPCA based on the sample covariance estimator does not work well if the data exhibits heavy-tailedness or outliers. To address this challenge, a new robust FPCA approach based on a functional pairwise spatial sign (PASS) operator, termed PASS FPCA, is introduced. We propose robust estimation procedures for eigenfunctions and eigenvalues. Theoretical properties of the PASS operator are established, showing that it adopts the same eigenfunctions as the standard covariance operator and also allows recovering ratios between eigenvalues. We also extend the proposed procedure to handle functional data measured with noise. Compared to existing robust FPCA approaches, the proposed PASS FPCA requires weaker distributional assumptions to conserve the eigenspace of the covariance function. Specifically, existing work are often built upon a class of functional elliptical distributions, which requires inherently symmetry. In contrast, we introduce a class of distributions called the weakly functional coordinate symmetry (weakly FCS), which allows for severe asymmetry and is much more flexible than the functional elliptical distribution family. The robustness of the PASS FPCA is demonstrated via extensive simulation studies, especially its advantages in scenarios with nonelliptical distributions. The proposed method was motivated by and applied to analysis of accelerometry data from the Objective Physical Activity and Cardiovascular Health Study, a large-scale epidemiological study to investigate the relationship between objectively measured physical activity and cardiovascular health among older women.
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Análisis de Componente Principal , Anciano , Femenino , Humanos , Acelerometría , Ejercicio Físico , Sistema CardiovascularRESUMEN
INTRODUCTION: Physical activity (PA) is prospectively inversely associated with dementia risk, but few studies examined accelerometer measures of PA and sitting with rigorously-adjudicated mild cognitive impairment (MCI) and dementia risk. METHODS: We examined the associations of accelerometer measures (PA and sitting) with incident MCI/probable dementia in the Women's Health Initiative (n = 1277; mean age = 82 ± 6 years) RESULTS: Over a median follow-up of 4.2 years, 267 MCI/probable dementia cases were identified. Adjusted Cox regression HRs (95% CI) across moderate-to-vigorous PA (MVPA) min/d quartiles were 1.00 (reference), 1.28 (0.90 to 1.81), 0.79 (0.53 to 1.17), and 0.69 (0.45 to 1.06); P-trend = 0.01. Adjusted HRs (95% CI) across steps/d quartiles were 1.00 (reference), 0.73 (0.51 to 1.03), 0.64 (0.43 to 0.94), and 0.38 (0.23 to 0.61); P-trend < 0.001. The HR (95% CI) for each 1-SD increment in MVPA (31 min/d) and steps/d (1865) were 0.79 (0.67 to 0.94) and 0.67 (0.54 to 0.82), respectively. Sitting was not associated with MCI/probable dementia. DISCUSSION: Findings suggest ≥ moderate intensity PA, particularly stepping, associates with lower MCI and dementia risk. HIGHLIGHTS: Few studies have examined accelerometer-measured physical activity, including steps, and sitting with incident ADRD. Moderate-to-vigorous physical activity and steps, but not light physical activity or sitting, were inversely associated with lower ADRD risk. Among older women, at least moderate intensity physical activity may be needed to reduce ADRD risk.
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Disfunción Cognitiva , Demencia , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/epidemiología , Ejercicio Físico/psicología , Salud de la Mujer , Acelerometría , Demencia/epidemiologíaRESUMEN
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.
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Aplicaciones Móviles , Cese del Hábito de Fumar , Conductas Relacionadas con la Salud , Humanos , Teléfono Inteligente , FumarRESUMEN
Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63-97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles = .01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend = .27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p = .03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults.
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Enfermedades Cardiovasculares , Acelerometría , Accidentes por Caídas/prevención & control , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico , Terapia por Ejercicio , Femenino , HumanosRESUMEN
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.
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Estudio de Asociación del Genoma Completo , Genómica , Modelos Genéticos , Neoplasias Colorrectales/genética , Biología Computacional , Simulación por Computador , Genes Relacionados con las Neoplasias , Humanos , Análisis Numérico Asistido por Computador , Programas InformáticosRESUMEN
Background: Evidence that higher sedentary time is associated with higher risk for cardiovascular disease (CVD) is based mainly on self-reported measures. Few studies have examined whether patterns of sedentary time are associated with higher risk for CVD. Methods: Women from the Objective Physical Activity and Cardiovascular Health (OPACH) Study (n=5638, aged 63-97, mean age=79±7) with no history of myocardial infarction (MI) or stroke wore accelerometers for 4-to-7 days and were followed for up to 4.9 years for CVD events. Average daily sedentary time and mean sedentary bout duration were the exposures of interest. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for CVD using models adjusted for covariates and subsequently adjusted for potential mediators (body mass index (BMI), diabetes, hypertension, and CVD-risk biomarkers [fasting glucose, high-density lipoprotein, triglycerides, and systolic blood pressure]). Restricted cubic spline regression characterized dose-response relationships. Results: There were 545 CVD events during 19,350 person-years. Adjusting for covariates, women in the highest (≥ ~11 hr/day) vs. the lowest (≤ ~9 hr/day) quartile of sedentary time had higher risk for CVD (HR=1.62; CI=1.21-2.17; p-trend <0.001). Further adjustment for potential mediators attenuated but did not eliminate significance of these associations (p-trend<.05, each). Longer vs. shorter mean bout duration was associated with higher risks for CVD (HR=1.54; CI=1.27-2.02; p-trend=0.003) after adjustment for covariates. Additional adjustment for CVD-risk biomarkers attenuated associations resulting in a quartile 4 vs. quartile 1 HR=1.36; CI=1.01-1.83; p-trend=0.10). Dose-response associations of sedentary time and bout duration with CVD were linear (P-nonlinear >0.05, each). Women jointly classified as having high sedentary time and long bout durations had significantly higher risk for CVD (HR=1.34; CI=1.08-1.65) than women with both low sedentary time and short bout duration. All analyses were repeated for incident coronary heart disease (MI or CVD death) and associations were similar with notably stronger hazard ratios. Conclusions: Both high sedentary time and long mean bout durations were associated in a dose-response manner with increased CVD risk in older women, suggesting that efforts to reduce CVD burden may benefit from addressing either or both component(s) of sedentary behavior.
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Enfermedades Cardiovasculares/epidemiología , Ejercicio Físico , Conducta Sedentaria , Salud de la Mujer , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Femenino , Estado de Salud , Estilo de Vida Saludable , Humanos , Incidencia , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Factores Sexuales , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Sedentary behavior (SB) is linked to negative health outcomes in older adults. Most studies use summary values, e.g., total sedentary minutes/day. Diurnal timing of SB accumulation may further elucidate SB-health associations. METHODS: Six thousand two hundred four US women (mean age = 79 ± 7; 50% White, 34% African-American) wore accelerometers for 7-days at baseline, yielding 41,356 person-days with > 600 min/day of data. Annual follow-up assessments of health, including physical functioning, were collected from participants for 6 years. A novel two-phase clustering procedure discriminated participants' diurnal SB patterns: phase I grouped day-level SB trajectories using longitudinal k-means; phase II determined diurnal SB patterns based on proportion of phase I trajectories using hierarchical clustering. Mixed models tested associations between SB patterns and longitudinal physical functioning, adjusted for covariates including total sedentary time. Effect modification by moderate-vigorous-physical activity (MVPA) was tested. RESULTS: Four diurnal SB patterns were identified: p1 = high-SB-throughout-the-day; p2 = moderate-SB-with-lower-morning-SB; p3 = moderate-SB-with-higher-morning-SB; p4 = low-SB-throughout-the-day. High MVPA mitigated physical functioning decline and correlated with better baseline and 6-year trajectory of physical functioning across patterns. In low MVPA, p2 had worse 6-year physical functioning decline compared to p1 and p4. In high MVPA, p2 had similar 6-year physical functioning decline compared to p1, p3, and p4. CONCLUSIONS: In a large cohort of older women, diurnal SB patterns were associated with rates of physical functioning decline, independent of total sedentary time. In particular, we identified a specific diurnal SB subtype defined by less SB earlier and more SB later in the day, which had the steepest decline in physical functioning among participants with low baseline MVPA. Thus, diurnal timing of SB, complementary to total sedentary time and MVPA, may offer additional insights into associations between SB and physical health, and provide physicians with early warning of patients at high-risk of physical function decline.
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Ritmo Circadiano , Rendimiento Físico Funcional , Conducta Sedentaria , Acelerometría/instrumentación , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Femenino , Humanos , Estudios Prospectivos , Dispositivos Electrónicos Vestibles , Salud de la Mujer/estadística & datos numéricosRESUMEN
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.
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Supervivientes de Cáncer/psicología , Glioma/psicología , Adulto , Niño , Escolaridad , Empleo , Femenino , Glioma/radioterapia , Glioma/cirugía , Humanos , Renta , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Hermanos , Clase SocialRESUMEN
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.
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Interacción Gen-Ambiente , Modelos Genéticos , Modelos Estadísticos , Análisis de Secuencia de ADN/estadística & datos numéricos , HumanosRESUMEN
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).
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Internet/instrumentación , Cese del Hábito de Fumar/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fumar , Factores de TiempoRESUMEN
Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012-2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women's Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.
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Ejercicio Físico/fisiología , Leucocitos/ultraestructura , Conducta Sedentaria , Telómero/ultraestructura , Acelerometría , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Autoinforme , Población BlancaRESUMEN
We study threshold regression models that allow the relationship between the outcome and a covariate of interest to change across a threshold value in the covariate. In particular, we focus on continuous threshold models, which experience no jump at the threshold. Continuous threshold regression functions can provide a useful summary of the association between outcome and the covariate of interest, because they offer a balance between flexibility and simplicity. Motivated by collaborative works in studying immune response biomarkers of transmission of infectious diseases, we study estimation of continuous threshold models in this article with particular attention to inference under model misspecification. We derive the limiting distribution of the maximum likelihood estimator, and propose both Wald and test-inversion confidence intervals. We evaluate finite sample performance of our methods, compare them with bootstrap confidence intervals, and provide guidelines for practitioners to choose the most appropriate method in real data analysis. We illustrate the application of our methods with examples from the HIV-1 immune correlates studies.
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Modelos Estadísticos , VIH-1 , Humanos , Funciones de VerosimilitudRESUMEN
Functional data arise frequently in biomedical studies, where it is often of interest to investigate the association between functional predictors and a scalar response variable. While functional linear models (FLM) are widely used to address these questions, hypothesis testing for the functional association in the FLM framework remains challenging. A popular approach to testing the functional effects is through dimension reduction by functional principal component (PC) analysis. However, its power performance depends on the choice of the number of PCs, and is not systematically studied. In this article, we first investigate the power performance of the Wald-type test with varying thresholds in selecting the number of PCs for the functional covariates, and show that the power is sensitive to the choice of thresholds. To circumvent the issue, we propose a new method of ordering and selecting principal components to construct test statistics. The proposed method takes into account both the association with the response and the variation along each eigenfunction. We establish its theoretical properties and assess the finite sample properties through simulations. Our simulation results show that the proposed test is more robust against the choice of threshold while being as powerful as, and often more powerful than, the existing method. We then apply the proposed method to the cerebral white matter tracts data obtained from a diffusion tensor imaging tractography study.
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Modelos Lineales , Imagen de Difusión Tensora , Análisis de Componente PrincipalRESUMEN
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.
Asunto(s)
Envejecimiento , Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico , Acelerometría , Anciano , Anciano de 80 o más Años , Etnicidad , Femenino , Servicios de Salud para Ancianos , Humanos , Persona de Mediana Edad , Proyectos de Investigación , Encuestas y Cuestionarios , Estados Unidos , Servicios de Salud para MujeresRESUMEN
BACKGROUND: The consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations. OBJECTIVE: We examined the association between variation across the genome and serum concentrations of lycopene in a multiethnic population. METHODS: Participants included African (n = 914), Hispanic (n = 464), and European (n = 1203) American postmenopausal women from the Women's Health Initiative. We analyzed â¼7 million single nucleotide polymorphisms (SNPs). Linear regression models were used to assess associations between each SNP and serum concentrations (log transformed, continuous) of lycopene; we adjusted for age, body mass index, and population substructure. Models were run separately by ethnicity, and results were combined in a transethnic fixed-effects meta-analysis. RESULTS: In the meta-analysis, the scavenger receptor class B, member 1 (SCARB1) gene, which encodes for a cholesterol membrane transporter, was significantly associated with lycopene concentrations (rs1672879; P < 2.68 × 10(-9)). Each additional G allele resulted in a 12% decrease in lycopene concentrations for African Americans, 20% decrease for Hispanic Americans, and 9% decrease for European Americans. In addition, 2 regions were significantly associated with serum lycopene concentrations in African Americans: the slit homolog 3 gene (SLIT3), which serves as a molecular guidance cue in cellular migration, and the dehydrogenase/reductase (SDR family) member 2 (DHRS2) gene, which codes for an oxidoreductase that mitigates the breakdown of steroids. CONCLUSIONS: We found 3 novel loci associated with serum lycopene concentrations, 2 of which were specific to African Americans. Future functional studies looking at these specific genes may provide insight into the metabolism and underlying function of lycopene in humans, which may further elucidate lycopene's influence on disease risk and health. This trial was registered at clinicaltrials.gov as NCT00000611.
Asunto(s)
Negro o Afroamericano/genética , Carotenoides/sangre , Variación Genética , Hispánicos o Latinos/genética , Población Blanca/genética , Anciano , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo , Alelos , Índice de Masa Corporal , Carbonil Reductasa (NADPH) , Colesterol/sangre , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Técnicas de Genotipaje , Humanos , Modelos Lineales , Licopeno , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Estudios Observacionales como Asunto , Polimorfismo de Nucleótido Simple , Posmenopausia , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Receptores Depuradores de Clase B/genética , Receptores Depuradores de Clase B/metabolismoRESUMEN
A threshold effect takes place in situations where the relationship between an outcome variable and a predictor variable changes as the predictor value crosses a certain threshold/change point. Threshold effects are often plausible in a complex biological system, especially in defining immune responses that are protective against infections such as HIV-1, which motivates the current work. We study two hypothesis testing problems in change point models. We first compare three different approaches to obtaining a p-value for the maximum of scores test in a logistic regression model with change point variable as a main effect. Next, we study the testing problem in a logistic regression model with the change point variable both as a main effect and as part of an interaction term. We propose a test based on the maximum of likelihood ratios test statistic and obtain its reference distribution through a Monte Carlo method. We also propose a maximum of weighted scores test that can be more powerful than the maximum of likelihood ratios test when we know the direction of the interaction effect. In simulation studies, we show that the proposed tests have a correct type I error and higher power than several existing methods. We illustrate the application of change point model-based testing methods in a recent study of immune responses that are associated with the risk of mother to child transmission of HIV-1.
Asunto(s)
Interpretación Estadística de Datos , Modificador del Efecto Epidemiológico , Funciones de Verosimilitud , Modelos Logísticos , Simulación por Computador , Infecciones por VIH/transmisión , VIH-1/inmunología , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Método de MontecarloRESUMEN
Total energy consumption and activity-related energy expenditure (AREE) estimates that have been calibrated using biomarkers to correct for measurement error were simultaneously associated with the risks of cardiovascular disease, cancer, and diabetes among postmenopausal women who were enrolled in the Women's Health Initiative at 40 US clinical centers and followed from 1994 to the present. Calibrated energy consumption was found to be positively related, and AREE inversely related, to the risks of various cardiovascular diseases, cancers, and diabetes. These associations were not evident in most corresponding analyses that did not correct for measurement error. However, an important analytical caveat relates to the role of body mass index (BMI) (weight (kg)/height (m)(2)). In the calibrated variable analyses, BMI was regarded, along with self-reported data, as a source of information on energy consumption and physical activity, and BMI was otherwise excluded from the disease risk models. This approach cannot be fully justified with available data, and the analyses herein imply a need for improved dietary and physical activity assessment methods and for longitudinal self-reported and biomarker data to test and relax modeling assumptions. Estimated hazard ratios for 20% increases in total energy consumption and AREE, respectively, were as follows: 1.49 (95% confidence interval: 1.18, 1.88) and 0.80 (95% confidence interval: 0.69, 0.92) for total cardiovascular disease; 1.43 (95% confidence interval: 1.17, 1.73) and 0.84 (95% confidence interval: 0.73, 0.96) for total invasive cancer; and 4.17 (95% confidence interval: 2.68, 6.49) and 0.60 (95% confidence interval: 0.44, 0.83) for diabetes.