A generalized linear mixed model for longitudinal binary data with a marginal logit link function

Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis [Biometrika 90 (2003) 765--775] proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall's $\tau$. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS390 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Sex differences in circumstances and consequences of outdoor and indoor falls in older adults in the MOBILIZE Boston cohort study

Background: Despite extensive research on risk factors associated with falling in older adults, and current fall prevention interventions focusing on modifiable risk factors, there is a lack of detailed accounts of sex differences in risk factors, circumstances and consequences of falls in the literature. We examined the circumstances, consequences and resulting injuries of indoor and outdoor falls according to sex in a population study of older adults. Methods: Men and women 65 years and older (N = 743) were followed for fall events from the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston prospective cohort study. Baseline measurements were collected by comprehensive clinical assessments, home visits and questionnaires. During the follow-up (median = 2.9 years), participants recorded daily fall occurrences on a monthly calendar, and fall circumstances were determined by a telephone interview. Falls were categorized by activity and place of falling. Circumstance-specific annualized fall rates were calculated and compared between men and women using negative binomial regression models. Results: Women had lower rates of outdoor falls overall (Crude Rate Ratio (RR): 0.72, 95% Confidence Interval (CI): 0.56-0.92), in locations of recreation (RR: 0.34, 95% CI: 0.17-0.70), during vigorous activity (RR: 0.38, 95% CI: 0.18-0.81) and on snowy or icy surfaces (RR: 0.55, 95% CI: 0.36-0.86) compared to men. Women and men did not differ significantly in their rates of falls outdoors on sidewalks, streets, and curbs, and during walking. Compared to men, women had greater fall rates in the kitchen (RR: 1.88, 95% CI: 1.04-3.40) and while performing household activities (RR: 3.68, 95% CI: 1.50-8.98). The injurious outdoor fall rates were equivalent in both sexes. Women’s overall rate of injurious indoor falls was nearly twice that of men’s (RR: 1.98, 95% CI: 1.44-2.72), especially in the kitchen (RR: 6.83, 95% CI: 2.05-22.79), their own home (RR: 1.84, 95% CI: 1.30-2.59) and another residential home (RR: 4.65, 95% CI: 1.05-20.66) or other buildings (RR: 2.29, 95% CI: 1.18-4.44). Conclusions: Significant sex differences exist in the circumstances and injury potential when older adults fall indoors and outdoors, highlighting a need for focused prevention strategies for men and women

Euglycemic Hyperinsulinemia Alters the Response to Orthostatic Stress in Older Adults With Type 2 Diabetes

OBJECTIVE—Insulin has opposing influences on blood pressure by simultaneously increasing adrenergic activity and vasodilatating peripheral blood vessels. In this study, we sought to determine whether hyperinsulinemia affects tilt table responses in older adults with type 2 diabetes not complicated by orthostatic hypotension

Patterns, Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background: Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. Methods: We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. Results: We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years. Conclusions: Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures

Fall Risk is Not Black and White

Objective: To determine whether previously reported racial differences in fall rates between White and Black/African American is explained by differences in health status and neighborhood characteristics. Design: Prospective cohort Setting: Community Participants: The study included 550 White and 116 Black older adults in the Greater Boston area (mean age: 78 years; 36% men) who were English-speaking, able to walk across a room, and without severe cognitive impairment. Measurements: Falls were prospectively reported using monthly fall calendars. The location of each fall and fall-related injuries were asked during telephone interviews. At baseline, we assessed risk factors for falls, including sociodemographic characteristics, physiologic risk factors, physical activity, and community-level characteristics. Results: Over the mean follow-up of 1,048 days, 1,539 falls occurred (incidence: 806/1,000 person-years). Whites were more likely than Blacks to experience any falls (867 versus 504 falls per 1,000 person-years; RR [95% CI]: 1.77 [1.33, 2.36]), outdoor falls (418 versus 178 falls per 1,000 person-years; 1.78 [1.08, 2.92]), indoor falls (434 versus 320 falls per 1,000 person-years; 1.44 [1.02, 2.05]), and injurious falls (367 versus 205 falls per 1,000 person-years; 1.79 [1.30, 2.46]). With exception of injurious falls, higher fall rates in Whites than Blacks were substantially attenuated with adjustment for risk factors and community-level characteristics: any fall (1.24 [0.81, 1.89]), outdoor fall (1.57 [0.86, 2.88]), indoor fall (1.08 [0.64, 1.81]), and injurious fall (1.77 [1.14, 2.74]). Conclusion: Our findings suggest that the racial differences in fall rates may be largely due to confounding by individual-level and community-level characteristics

Geographic Variation Within the Military Health System

Background: This study seeks to quantify variation in healthcare utilization and per capita costs using system-defined geographic regions based on enrollee residence within the Military Health System (MHS). Methods: Data for fiscal years 2007 – 2010 were obtained from the Military Health System under a data sharing agreement with the Defense Health Agency (DHA). DHA manages all aspects of the Department of Defense Military Health System, including TRICARE. Adjusted rates were calculated for per capita costs and for two procedures with high interest to the MHS- back surgery and Cesarean sections for TRICARE Prime and Plus enrollees. Coefficients of variation (CoV) and interquartile ranges (IQR) were calculated and analyzed using residence catchment area as the geographic unit. Catchment areas anchored by a Military Treatment Facility (MTF) were compared to catchment areas not anchored by a MTF. Results: Variation, as measured by CoV, was 0.37 for back surgery and 0.13 for C-sections in FY 2010- comparable to rates documented in other healthcare systems. The 2010 CoV (and average cost) for per capita costs was 0.26 ($3,479.51). Procedure rates were generally lower and CoVs higher in regions anchored by a MTF compared with regions not anchored by a MTF, based on both system-wide comparisons and comparisons of neighboring areas. Conclusions: In spite of its centrally managed system and relatively healthy beneficiaries with very robust health benefits, the MHS is not immune to unexplained variation in utilization and cost of healthcare

Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR

The increase of the functional entropy of the human brain with age

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy

Persistent fluctuations in stride intervals under fractal auditory stimulation

Copyright @ 2014 Marmelat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.Commission of the European Community and the Netherlands Organisation for Scientific Research