NONPARAMETRIC ESTIMATION OF BIVARIATE FAILURE TIME ASSOCIATIONS IN THE PRESENCE OF A COMPETING RISK

There has been much research on the study of associations among paired failure times. Most has either assumed time invariance of association or been based on complex measures or estimators. Little has accommodated failures arising amid competing risks. This paper targets the conditional cause specific hazard ratio, a recent modification of the conditional hazard ratio to accommodate competing risks data. Estimation is accomplished by an intuitive, nonparametric method that localizes Kendall’s tau. Time variance is accommodated through a partitioning of space into “bins” between which the strength of association may differ. Inferential procedures are researched, small sample performance evaluated, and methods applied to investigate familial association in dementia onset. The proposed methodology augments existing methodology with an approach that may be more readily applied and interpreted, thus facilitate dissemination of methodology addressing failure time associations into the substantive literatur

Multilevel Latent Class Models with Dirichlet Mixing Distribution

Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we develop multilevel latent class model, in which subpopulation mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when either the number of classes or the cluster size is large. We propose a maximum pairwise likelihood (MPL) approach via a modified EM algorithm for this case. We also show that a simple latent class analysis, combined with robust standard errors, provides another consistent, robust, but less efficient inferential procedure. Simulation studies suggest that the three methods work well in finite samples, and that the MPL estimates often enjoy comparable precision as the ML estimates. We apply our methods to the analysis of comorbid symptoms in the Obsessive Compulsive Disorder study. Our models\u27 random effects structure has more straightforward interpretation than those of competing methods, thus should usefully augment tools available for latent class analysis of multilevel data

MODELING DIFFERENTIATED TREATMENT EFFECTS FOR MULTIPLE OUTCOMES DATA

Multiple outcomes data are commonly used to characterize treatment effects in medical research, for instance, multiple symptoms to characterize potential remission of a psychiatric disorder. Often either a global, i.e. symptom-invariant, treatment effect is evaluated. Such a treatment effect may over generalize the effect across the outcomes. On the other hand individual treatment effects, varying across all outcomes, are complicated to interpret, and their estimation may lose precision relative to a global summary. An effective compromise to summarize the treatment effect may be through patterns of the treatment effects, i.e. differentiated effects. In this paper we propose a two-category model to differentiate treatment effects into two groups. A model fitting algorithm and simulation study are presented, and several methods are developed to analyze heterogeneity presenting in the treatment effects. The method is illustrated using an analysis of schizophrenia symptom data

Relationship between continuity of care and adverse outcomes varies by number of chronic conditions among older adults with diabetes

Background: Continuity of care is a basic tenant of primary care practice. However, the evidence on the importance of continuity of care for older adults with complex conditions is mixed. Objective: To assess the relationship between measurement of continuity of care, number of chronic conditions, and health outcomes. Design: We analyzed data from a cohort of 1,600 US older adults with diabetes and ≥1 other chronic condition in a private Medicare health plan from July 2010 to December 2011. Multivariate regression models were used to examine the association of baseline continuity (the first 6 months) and the composite outcome of any emergency room use or inpatient hospitalization occurring in the following 12-month period. Results: After adjusting for baseline covariates, high known provider continuity (KPC) was associated with an 84% (adjusted odds ratio 0.16; 95% confidence interval 0.09–0.26) reduction in the risk of the composite outcome. High KPC was significantly associated with a lower risk of the composite outcome among individuals with ≥6 conditions. However, the usual provider of care and continuity of care indices were not significantly related with the composite outcome in the overall sample or in those with ≥6 conditions. Conclusion: The relationship between continuity of care and adverse outcomes depends on the measure of continuity of care employed. High morbidity patients are more likely to benefit from continuity of care interventions as measured by the KPC, which measures the proportion of a patient’s visits that are with the same providers over time. Journal of Comorbidity 2016;6(2):65–7

SURROGATE SCREENING MODELS FOR THE LOW PHYSICAL ACTIVITY CRITERION OF FRAILTY

Background and Aims. Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women’s Health and Aging Study (WHAS). Methods. Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by “relative influence” in predicting low physical activity. We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. Results. Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. Conclusions. We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included

A prospective, population-based study of the role of visual impairment in motor vehicle crashes among older drivers: the SEE study.

PURPOSE: To determine the role of vision and visual attention factors in automobile crash involvement. METHODS: Drivers aged 65 to 84 years were identified during the baseline interview (1993-1995) of the Salisbury Eye Evaluation (SEE) Study. Crash involvement through December 1997 was determined from Maryland State motor vehicle records. Vision tests at baseline included distance acuity at normal and low luminance, contrast sensitivity, glare sensitivity, stereoacuity, and visual fields. Visual attention was evaluated with the Useful Field of View Test (UFOV; Visual Awareness, Chicago, IL). Survival analysis was used to determine the relative risk of a crash as a function of demographic variables, miles driven, vision, and visual attention. RESULTS: One hundred twenty (6.7%) of the 1801 drivers were involved in a crash during the observation interval. Glare sensitivity and binocular field loss were significant predictors of crash involvement (P < 0.05). For those with moderate or better vision (<3 letters for glare sensitivity and <20 points missed for binocular visual fields) increased glare sensitivity or reduced visual fields were, paradoxically, associated with a reduction in crash risk, whereas for those with poorer levels of vision, increased glare sensitivity or reduced visual fields were associated with increased crash risk. Worse UFOV score was associated with increased crash risk. CONCLUSIONS: Glare sensitivity, visual field loss, and UFOV were significant predictors of crash involvement. Acuity, contrast sensitivity, and stereoacuity were not associated with crashes. These results suggest that current vision screening for drivers' licensure, based primarily on visual acuity, may miss important aspects of visual impairment

Systemic inflammation, body composition, and physical performance in old community-dwellers

Background Chronic inflammation, changes in body composition, and declining physical function are hallmarks of the ageing process. The aim of the present study was to provide a preliminary characterisation of the relationship among these age-related phenomena via multivariate modelling. Methods Thirty-five old adults (OAs) and 17 young adults (YAs) were enrolled. The volume of skeletal muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) of the thigh was quantified by three-dimensional magnetic resonance imaging. Muscle strength was measured by knee extension strength testing. In OAs, physical performance was further assessed via the Short Physical Performance Battery (SPPB). Multi-block partial least squares-discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory profiles and functional and imaging parameters. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. Results The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 92.3% in calibration (94.1% in YAs and 91.4% in OAs), 84.6% in internal validation (95.3% in YAs and 78.5% in OAs), and 82.6% in external validation (94% in YAs and 76.9% in OAs). Relative to YAs, OAs were characterised by smaller muscle volume, greater IMAT volume, lower muscle strength, and higher levels of myeloperoxidase, P-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Compared with OAs with SPPB &gt;8, those scoring 8 were characterised by smaller muscle volume, greater SAT volume, lower muscle strength, and higher levels of interleukin 1 beta, 6, 10, 12, 13, tumour necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor. Conclusions Multi-block PLS-DA identified distinct patterns of relationships among circulating cytokines and functional and imaging parameters in persons of different ages and varying levels of physical performance. The longitudinal implementation of such an innovative strategy could allow for the tracking of health status over time, the early detection of deviations in health trajectories, and the monitoring of response to treatments

Prevalence of frailty and disability:findings from the English Longitudinal Study of Ageing

OBJECTIVE: to examine the prevalence of frailty and disability in people aged 60 and over and the proportion of those with disabilities who receive help or use assistive devices.METHODS: participants were 5,450 people aged 60 and over from the English Longitudinal Study of Ageing. Frailty was defined according to the Fried criteria. Participants were asked about difficulties with mobility or other everyday activities. Those with difficulties were asked whether they received help or used assistive devices.RESULTS: the overall weighted prevalence of frailty was 14%. Prevalence rose with increasing age, from 6.5% in those aged 60-69 years to 65% in those aged 90 or over. Frailty occurred more frequently in women than in men (16 versus 12%). Mobility difficulties were very common: 93% of frail individuals had such difficulties versus 58% of the non-frail individuals. Among frail individuals, difficulties in performing activities or instrumental activities of daily living were reported by 57 or 64%, respectively, versus 13 or 15%, respectively, among the non-frail individuals. Among those with difficulties with mobility or other daily activities, 71% of frail individuals and 31% of non-frail individuals said that they received help. Of those with difficulties, 63% of frail individuals and 20% of non-frail individuals used a walking stick, but the use of other assistive devices was uncommon.CONCLUSIONS: frailty becomes increasingly common in older age groups and is associated with a sizeable burden as regards difficulties with mobility and other everyday activities.<br/

Association of IGF-I Levels with Muscle Strength and Mobility in Older Women

The functional consequences of the age-associated decline in IGF-I are unknown. We hypothesized that low IGF-I levels in older women would be associated with poor muscle strength and mobility. We assessed this question in a population representative of the full spectrum of health in the community, obtaining serum IGF-I levels from women aged 70–79 yr, enrolled in the Women’s Health and Aging Study I or II. Cross-sectional analyses were performed using 617 women with IGF-I levels drawn within 90 d of measurement of outcomes. After adjustment for age, there was an association between IGF-I and knee extensor strength (P = 0.004), but not anthropometry or other strength measures. We found a positive relationship between IGF-I levels and walking speed for IGF-I levels below 50 μg/liter (P < 0.001), but no relationship above this threshold. A decline in IGF-I level was associated with self-reported difficulty in mobility tasks. All findings were attenuated after multivariate adjustment. In summary, in a study population including frail and healthy older women, low IGF-I levels were associated with poor knee extensor muscle strength, slow walking speed, and self-reported difficulty with mobility tasks. These findings suggest a role for IGF-I in disability as well as a potential target population for interventions to raise IGF-I levels