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

Structure calculation, refinement and validation using CcpNmr Analysis

CcpNmr Analysis provides a streamlined pipeline for both NMR chemical shift assignment and structure determination of biological macromolecules. In addition, it encompasses tools to analyse the many additional experiments that make NMR such a pivotal technique for research into complex biological questions. This report describes how CcpNmr Analysis can seamlessly link together all of the tasks in the NMR structure-determination process. It details each of the stages from generating NMR restraints [distance, dihedral,hydrogen bonds and residual dipolar couplings (RDCs)],exporting these to and subsequently re-importing them from structure-calculation software (such as the programs CYANA or ARIA) and analysing and validating the results obtained from the structure calculation to, ultimately, the streamlined deposition of the completed assignments and the refined ensemble of structures into the PDBe repository. Until recently, such solution-structure determination by NMR has been quite a laborious task, requiring multiple stages and programs. However, with the new enhancements to CcpNmr Analysis described here, this process is now much more intuitive and efficient and less error-prone

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

Ambient Air Pollution and Depressive Symptoms in Older Adults: Results from the MOBILIZE Boston Study

Background: Exposure to ambient air pollution, particularly from traffic, has been associated with adverse cognitive outcomes, but the association with depressive symptoms remains unclear. Objectives: We investigated the association between exposure to ambient air and traffic pollution and the presence of depressive symptoms among 732 Boston-area adults ≥ 65 years of age (78.1 ± 5.5 years, mean ± SD). Methods: We assessed depressive symptoms during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). We estimated residential distance to the nearest major roadway as a marker of long-term exposure to traffic pollution and assessed short-term exposure to ambient fine particulate matter (PM2.5), sulfates, black carbon (BC), ultrafine particles, and gaseous pollutants, averaged over the 2 weeks preceding each assessment. We used generalized estimating equations to estimate the odds ratio (OR) of a CESD-R score ≥ 16 associated with exposure, adjusting for potential confounders. In sensitivity analyses, we considered CESD-R score as a continuous outcome and mean annual residential BC as an alternate marker of long-term exposure to traffic pollution. Results: We found no evidence of a positive association between depressive symptoms and long-term exposure to traffic pollution or short-term changes in pollutant levels. For example, we found an OR of CESD-R score ≥ 16 of 0.67 (95% CI: 0.46, 0.98) per interquartile range (3.4 μg/m3) increase in PM2.5 over the 2 weeks preceding assessment. Conclusions: We found no evidence suggesting that ambient air pollution is associated with depressive symptoms among older adults living in a metropolitan area in attainment of current U.S. regulatory standards. Citation: Wang Y, Eliot MN, Koutrakis P, Gryparis A, Schwartz JD, Coull BA, Mittleman MA, Milberg WP, Lipsitz LA, Wellenius GA. 2014. Ambient air pollution and depressive symptoms in older adults: results from the MOBILIZE Boston Study. Environ Health Perspect 122:553–558; http://dx.doi.org/10.1289/ehp.120590

The yield of head CT in syncope: a pilot study

Although head CT is often routinely performed in emergency department (ED) patients with syncope, few studies have assessed its value

Hidden Disunities and Uncanny Resemblances: Connections and Disconnections in the Music of Lera Auerbach and Michael Nyman

Does stylistic appropriation serve to create a sense of unity or disunity, continuity or fragmentation? Taking George Lipsitz's notion of �families of resemblance� and intertextuality's dialogic qualities (as shown in the writings of Mikhail Bakhtin and Julia Kristeva), this article will put forward the argument that certain forms of quotation result in a kind of halfway house�an in-between state�where the text seemingly announces its own independence despite its (inter)dependence on a whole host of other intertexts. Unlike the collage-like, so-called polystylistic compositions of the late 1960s, which also used quotation, an altogether different and more deeply embedded form has developed since then, where the quoted material is integrated to a much greater extent on the surface, only to lay bare its �difference� at a deeper level. Such �hidden discontinuities� will be examined in relation to a single work, Lera Auerbach's Sogno di Stabat Mater (2005/2008), before applying Lipsitz's principle as a case study to Michael Nyman's oeuvre

Predicting risk of hospital and emergency department use for home care elderly persons through a secondary analysis of cross-national data

Abstract Background Older adults remain the highest utilization group with unplanned visits to emergency departments and hospital admissions. Many have considered what leads to this high utilization and the answers provided have depended upon the independent measures available in the datasets used. This project was designed to further understanding of the reasons for older adult ED visits and admissions to acute care hospitals. Methods A secondary analysis of data from a cross-national sample of community residing elderly, 60 years of age or older, and most of whom received services from a local home-care program was conducted. The assessment instrument used in this study is the interRAI HC (home care), designed for use in assessing elderly home care recipients. The model specification stage of the study identified the baseline independent variables that do and do not predict the follow-up measure of hospitalization and ED use. Stepwise logistic regression was used next to identify characteristics that best identified elders who subsequently entered a hospital or visited an ED. The items generated from the final multivariate logistic equation using the interRAI home care measures comprise the interRAI Hospital-ED Risk Index. Results Independent measures in three key domains of clinical complications, disease diagnoses and specialized treatments were related to subsequent hospitalization or ED use. Among the eighteen clinical complication measures with higher, meaningful odds ratios are pneumonia, urinary tract infection, fever, chest pain, diarrhea, unintended weight loss, a variety of skin conditions, and subject self-reported poor health. Disease diagnoses with a meaningful relationship with hospital/ED use include coronary artery disease, congestive heart failure, cancer, emphysema and renal failure. Specialized treatments with the highest odds ratios were blood transfusion, IV infusion, wound treatment, radiation and dialysis. Two measures, Alzheimer’s disease and day care appear to have a protective effect for hospitalization/ED use with lower odds ratios. Conclusions Examination into “preventable” hospitalizations and re-hospitalizations for older adults who have the highest rates of utilization are occurring beneath an umbrella of assuring the highest quality of care and controlling costs. The interRAI Hospitalization-ED Risk Index offers an effective approach to predicting hospitalization utilization among community dwelling older adults.http://deepblue.lib.umich.edu/bitstream/2027.42/109520/1/12913_2014_Article_519.pd

Predictors of Mortality Up to 1 Year After Emergency Major Abdominal Surgery in Older Adults

ackground The number of older patients who undergo emergent major abdominal procedures is expected to increase yet little is known about mortality beyond 30 days after surgery. Objective Identify factors associated with mortality among older patients at 30, 180 and 365 days after emergency major abdominal surgery. Design A retrospective study of the Health and Retirement Study (HRS) linked to Medicare Claims from 2000-2010. Setting N/A Participants Medicare beneficiaries > 65.5 years enrolled in the Health and Retirement Study (HRS) from 2000-2010, with at least one urgent/emergent major abdominal surgery and a core interview from the HRS within 3 years prior to surgery. Main Outcomes and Measures Survival analysis was used to describe all-cause mortality at 30, 180 and 365 days after surgery. Complementary log-log regression was used to identify patient characteristics and postoperative events associated with worse survival. Results 400 patients had one of the urgent/emergent surgeries of interest. Of these 24% were > 85 years; 50% had coronary artery disease, 48% had cancer, and 33% had congestive heart failure; and 37% experienced a postoperative complication. Postoperative mortality was 20%, 31% and 34% at 30, 180 days and 365 days. Among those > 85 years, 50% were dead one year after surgery. After multivariate adjustment including postoperative complications, dementia (Hazard ratio (HR) 2.02, 95%CI 1.24-3.31), hospitalization within 6 months before surgery (HR 1.63, 95% CI 1.12-2.28) and complications (HR 3.45, 95%CI (2.32-5.13) were independently associated with worse one-year survival. Conclusion Overall mortality is high up to one year after surgery in many older patients undergoing emergency major abdominal surgery. The occurrence of a complication is the clinical factor most strongly associated with worse survival

Interictal Spiking Increases with Sleep Depth in Temporal Lobe Epilepsy

Purpose : To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. Methods: At the time of study, subjects were seizure-free for 224 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. Conclusions: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65422/1/j.1528-1157.1998.tb01329.x.pd

Sustained Benefit of Alternate Behavioral Interventions to Improve Hypertension Control: A Randomized Clinical Trial

Little is known about the long-term effects of behavioral interventions to improve blood pressure (BP) control. We evaluated whether a telephone-delivered, behavioral stage-matched intervention (SMI), or a nontailored health education intervention (HEI) delivered for 6 months improves BP control (or lowers systolic BP) over 12 months, as well as its sustainability 6 months after intervention implementation ended, compared with usual care in participants with repeated uncontrolled BP at baseline. A 3-arm, randomized controlled trial was designed to evaluate the effectiveness of 2 interventions, each compared with a usual-care control group. Participants were 533 adults with persistent uncontrolled BP who were treated at 2 Veterans Affairs Medical Centers. The intervention was implemented for 6 months, followed by 6 months of observation. Compared with usual care, the odds of having BP under control over 12 months in SMI were 84% higher (odds ratio, 1.84 [95% CI, 1.28–2.67]; P=0.001), and 48% higher in HEI (odds ratio, 1.48 [95% CI, 1.02–2.14]; P=0.04).Over the 12 months, compared with usual care, systolic blood pressure was 2.80 mm Hg lower in SMI ([95% CI, 0.27 to 5.33]; P=0.03) while it was 2.58 mm Hg lower in HEI ([95% CI, −0.40 to 5.55]; P=0.09). From 6 to 12 months, SMI sustained improved BP control and lower systolic blood pressure, while HEI, which did not have significantly better BP control or lower systolic blood pressure at 6 months, appeared to improve BP control and lower systolic blood pressure. SMI and HEI are promising interventions that can be implemented in clinical practice to improve BP management