Multiple imputation for estimating hazard ratios and predictive abilities in case-cohort surveys

<p>Abstract</p> <p>Background</p> <p>The weighted estimators generally used for analyzing case-cohort studies are not fully efficient and naive estimates of the predictive ability of a model from case-cohort data depend on the subcohort size. However, case-cohort studies represent a special type of incomplete data, and methods for analyzing incomplete data should be appropriate, in particular multiple imputation (MI).</p> <p>Methods</p> <p>We performed simulations to validate the MI approach for estimating hazard ratios and the predictive ability of a model or of an additional variable in case-cohort surveys. As an illustration, we analyzed a case-cohort survey from the Three-City study to estimate the predictive ability of D-dimer plasma concentration on coronary heart disease (CHD) and on vascular dementia (VaD) risks.</p> <p>Results</p> <p>When the imputation model of the phase-2 variable was correctly specified, MI estimates of hazard ratios and predictive abilities were similar to those obtained with full data. When the imputation model was misspecified, MI could provide biased estimates of hazard ratios and predictive abilities. In the Three-City case-cohort study, elevated D-dimer levels increased the risk of VaD (hazard ratio for two consecutive tertiles = 1.69, 95%CI: 1.63-1.74). However, D-dimer levels did not improve the predictive ability of the model.</p> <p>Conclusions</p> <p>MI is a simple approach for analyzing case-cohort data and provides an easy evaluation of the predictive ability of a model or of an additional variable.</p

Transitions and trajectories in frailty states over time: a systematic review of the European Joint Action ADVANTAGE

Introduction. Frailty is a dynamic syndrome and may be reversible. Despite this, little is known about trajectories or transitions between different stages of frailty. Methods. A systematic review was conducted, selecting studies reporting frailty trajectories or transition states for adults in any settings in European ADVANTAGE Joint Action Member States. Results. Only three papers were included. Data were from longitudinal communitybased cohorts in the United Kingdom, Netherlands and Italy. The English study investigated the effect of physical activity on the progression of frailty over a 10-year period. Two presented data on the proportion of participants experiencing at least one frailty transition over time (32.6% in the Italian sample aged ≥ 65 years followed for 4.4 years; 34.3% in the Dutch sample aged 65-75 years, followed for 2 years). Conclusions. Data on frailty trajectories and transition states were limited and heterogeneous. Well-designed prospective studies and harmonized approaches to data collection are now needed

Hormone Treatment, Estrogen Receptor Polymorphisms and Mortality: A Prospective Cohort Study

International audienceBACKGROUND: The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18-0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23-8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572. CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT

Prevalence of frailty at population level in European ADVANTAGE Joint Action Member States: a systematic review and meta-analysis

Introduction. Although frailty is common among community-dwelling older adults, its prevalence in Europe and how this varies between countries is unclear. Methods. A systematic review and meta-analysis of literature on frailty prevalence in 22 European countries involved in the Joint Action ADVANTAGE was conducted. Results. Sixty-two papers, representing 68 unique datasets were included. Meta-analysis showed an overall estimated frailty prevalence of 18% (95% confidence interval, CI, 15- 21%). The prevalence in community (n = 53) vs non-community based studies (n = 15) was 12% (95% CI 10-15%) and 45% (95% CI 27-63%), respectively. Pooled prevalence in community studies adopting a physical phenotype was 12% (95% CI 10-14%, n = 45) vs 16% (95% CI 7-29%, n = 8) for all other definitions. Sub-analysis of a subgroup of studies assessed as high-quality (n = 47) gave a pooled estimate of 17% (95% CI 13-21%). Conclusions. The considerable and significant heterogeneity found warrants the development of common methodological approaches to provide accurate and comparable frailty prevalence estimates at population-level

Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging

BACKGROUND: Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. METHODS: We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. RESULTS: In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. CONCLUSION: There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved

Estimating and characterizing the burden of multimorbidity in the community: A comprehensive multistep analysis of two large nationwide representative surveys in France

10.1371/journal.pmed.1003584PLOS MEDICINE18

Dimensionality and invariance of ADL, IADL, BI-M2/WG-SS, and GALI in large surveys in France (2008–2014) and implications for measuring disability in epidemiology

Abstract Background The epidemiological investigation and surveillance of disability requires well-constructed, invariant, and, if possible, exchangeable measures. However, the current or recommended measures have not been thoroughly investigated with respect to these issues. Here we examined the dimensional structure and invariance of four measures across sociodemographic groups: Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Budapest Initiative Mark 2 (BI-M2) and Washington Group on Disability Statistics Short Set (WG-SS), and Global Activity Limitation Indicator (GALI). Methods We used data from three large nationwide representative surveys conducted in France between 2008 and 2014. The surveys included these four measures and classical and modern approaches (correlations, principal component analysis, Rasch modeling) were used to assess their dimensional structure as well as their invariance through differential item functioning (DIF) for sociodemographic characteristics. Polytomous logistic regression models were used to assess gradients in health inequalities associated with these measures. Results For many items of ADL, IADL, and BI-M2/WG-SS, we consistently observed disordered response thresholds, rejection of unidimensionality, and DIF evidence for sociodemographic characteristics across the survey samples. Health inequality gradients were erratic. In addition, it was impossible to identify a common continuum for GALI, ADL, IADL, and BI-M2/WG-SS or their constituent items. Conclusion This study warns against the current practice of investigating disability in epidemiology using measures that are unsuitable for epidemiological use, incommensurable, and inadequate regarding the basic requisites of dimensionality and invariance. Developing invariant measures and equating them along a common continuum to enlarge the common bases of measurement should therefore be a priority

Synergism between non-O blood group and oral estrogen in the risk of venous thromboembolism among postmenopausal women: The ESTHER study.: Bloog group, hormone therapy and risk of venous thromboembolis

International audienc

Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort.

OBJECTIVES: To assess the effects of treatment for memory impairment and the Ginkgo biloba extract (EGb 761) on dementia, mortality, and survival without dementia. DESIGN: Prospective community-based cohort study. SETTING: France. PARTICIPANTS: Three thousand five hundred thirty-four subjects aged 65 and older. MEASUREMENTS: Information on drug consumption was obtained by interview and visual assessment of patients' medicine chests. Active screening of dementia was performed every 2 years over a 13-year period. The independent effects of treatment for memory impairment and the Ginkgo biloba extract on the risks of dementia and death were estimated using Cox proportional hazards models, adjusted for potentially confounding factors (including comorbidities). RESULTS: The initial consumption of Ginkgo biloba did not modify the risk of dementia (relative risk (RR)=1.16, 95% confidence interval (CI)=0.84-1.60), whereas the consumption of other treatments for memory impairment was associated with a higher risk of dementia (RR=1.35, 95% CI=1.11-1.63). Subjects who took Ginkgo biloba had a significantly lower risk of mortality in the long term (RR=0.76, 95% CI=0.62-0.93), even after adjustment for potentially confounding factors. The initial consumption of treatment for memory impairment other than Ginkgo biloba did not modify the risk of mortality. CONCLUSION: These results suggest that treatment with EGb 761 may increase the probability of survival in the elderly population. These findings need to be corroborated and further assessed using randomized, controlled trials