OBJECTIVES. Many contextual analyses that bridge the micro-level-macro-level gap in identifying risk factors for adverse outcomes have not used methods appropriate for multilevel data. The purpose of this paper is to illustrate the application of appropriate multi-level analytic methods and discuss their implications for public health. METHODS. A previously published individual-level model of physical violence perpetrated by male partners during the childbearing year was reanalyzed to include variables describing the neighborhoods where the women resided. Logistic regression with estimation methods of the generalized estimating equation was used for the contextual analysis. To assess the advantages of the generalized estimating equation over conventional logistic regression, both were used for the two-level model. RESULTS. The regression coefficients from the contextual model differed from the betas obtained in the individual-level model. Not only were neighborhood-level variables related to the risk of partner-perpetrated violence, but the presence of these macro-level variables in the models modified the relationships of the individual-level variables to the risk of violence. CONCLUSIONS. Two-level models that include individual- and community-level factors may be beneficial for purposes of explanation in public health research.

Importance-Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, highrisk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.Objectives-To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics.Copyright 2014 American Medical Association. All rights reserved.Corresponding Author: Dorry L. Segev, MD, PhD, Department of Transplant Surgery, Johns Hopkins Medical Institutions, 720 Rutland Ave, Ross 771B, Baltimore, MD 21205 (dorry@jhmi.edu). Author Contributions: Dr Muzaale had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Muzaale and Massie contributed equally to this article. Disclaimer:The analyses described herein are the responsibility of the authors alone and do not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government. Conclusions and Relevance-Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation. HHS Public AccessEvery year in the United States, approximately 6000 healthy adults accept the risks of donor nephrectomy to help family members, friends, or even strangers improve survival and quality of life. 1 It is imperative that the transplant community, in due diligence to donors, understands the risk of donation to the fullest extent possible and communicates known risks to those considering donation. 2,3 To date, studies have shown that perioperative death is extremely rare and subsequent survival rates are comparable with healthy nondonors. [4][5][6] However, physiologic sequelae resulting from kidney donation remain less well characterized. Recent single-center 7-9 and nationwide 10 studies suggest that live donors do not have increased risk of end-stage renal disease (ESRD) compared with the general population; however, the general population is unscreened and, as such, at higher inherent risk of ESRD than carefully screened donors. Limited by small sample sizes and lack of a healthy comparison group, previous studies have been unable to compare the risk of ESRD that a healthy individual faces after donation with the risk that individual would have faced had he or she not donated. 11 Also, although studies show higher risk of ESRD in donor subgroups including black donors 10 compared with nonblack donors and male donors 8,9 compared with female donors, these studies comparing do...

We examined if baseline level of cognitive reserve (CR) and of Alzheimer’s disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n=303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed Mild Cognitive Impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau and neurodegeneration. Higher CR scores were associated with better cognitive performance, but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI prior to symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline.

In prospective cohort studies individuals are sometimes recruited according to a certain cross-sectional sampling criterion. A prevalent cohort is defined as a group of individuals who have a certain disease at enrollment into the study. Statistical models for the analysis of prevalent cohort data are considered when the onset or diagnosis time of the disease is known. The incident proportional hazards model, where the time scale is duration with disease, is compared to the prevalent proportional hazards model, where the fundamental time scale is follow-up time. In certain cases the time of enrollment may coincide with another event (such as the initiation of treatment). This situation is also considered and its limitations highlighted. To illustrate the methodological ideas discussed in the paper, the analysis of data from an observational study of zidovudine (ZVD) in patients with the acquired immunodeficiency syndrome (AIDS) is presented.

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Introduction Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments. Methods We describe the development of a multi‐center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid‐based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16‐month intervals), as well as genetic modifiers of AD risk and progression. Results Approximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided. Discussion This represents the largest U.S.‐based, multi‐site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population.

This study evaluated the utility of baseline and longitudinal MRI measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by Apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow-up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE-ε4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE-ε4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of AD.