Estimating piecewise exponential frailty model with changing prior for baseline hazard function
NASA Astrophysics Data System (ADS)
Thamrin, Sri Astuti; Lawi, Armin
2016-02-01
Piecewise exponential models provide a very flexible framework for modelling univariate survival data. It can be used to estimate the effects of different covariates which are influenced by the survival data. Although in a strict sense it is a parametric model, a piecewise exponential hazard can approximate any shape of a parametric baseline hazard. In the parametric baseline hazard, the hazard function for each individual may depend on a set of risk factors or explanatory variables. However, it usually does not explain all such variables which are known or measurable, and these variables become interesting to be considered. This unknown and unobservable risk factor of the hazard function is often termed as the individual's heterogeneity or frailty. This paper analyses the effects of unobserved population heterogeneity in patients' survival times. The issue of model choice through variable selection is also considered. A sensitivity analysis is conducted to assess the influence of the prior for each parameter. We used the Markov Chain Monte Carlo method in computing the Bayesian estimator on kidney infection data. The results obtained show that the sex and frailty are substantially associated with survival in this study and the models are relatively quite sensitive to the choice of two different priors.
Akazawa, K; Nakamura, T; Moriguchi, S; Shimada, M; Nose, Y
1991-07-01
Small sample properties of the maximum partial likelihood estimates for Cox's proportional hazards model depend on the sample size, the true values of regression coefficients, covariate structure, censoring pattern and possibly baseline hazard functions. Therefore, it would be difficult to construct a formula or table to calculate the exact power of a statistical test for the treatment effect in any specific clinical trial. The simulation program, written in SAS/IML, described in this paper uses Monte-Carlo methods to provide estimates of the exact power for Cox's proportional hazards model. For illustrative purposes, the program was applied to real data obtained from a clinical trial performed in Japan. Since the program does not assume any specific function for the baseline hazard, it is, in principle, applicable to any censored survival data as long as they follow Cox's proportional hazards model.
Defining the baseline for inhibition concentration calculations for hormetic hazards.
Bailer, A J; Oris, J T
2000-01-01
The use of endpoint estimates based on modeling inhibition of test organism response relative to a baseline response is an important tool in the testing and evaluation of aquatic hazards. In the presence of a hormetic hazard, the definition of the baseline response is not clear because non-zero levels of the hazard stimulate an enhanced response prior to inhibition. In the present study, the methodology and implications of how one defines a baseline response for inhibition concentration estimation in aquatic toxicity tests was evaluated. Three possible baselines were considered: the control response level; the pooling of responses, including controls and all concentration conditions with responses enhanced relative to controls; and, finally, the maximal response. The statistical methods associated with estimating inhibition relative to the first two baseline definitions were described and a method for estimating inhibition relative to the third baseline definition was derived. These methods were illustrated with data from a standard aquatic zooplankton reproductive toxicity test in which the number of young produced in three broods of a cladoceran exposed to effluent was modeled as a function of effluent concentration. Copyright 2000 John Wiley & Sons, Ltd.
McDermott, Mary McGrae; Ferrucci, Luigi; Simonsick, Eleanor M; Balfour, Jennifer; Fried, Linda; Ling, Shari; Gibson, Daniel; Guralnik, Jack M
2002-02-01
To define the association between baseline ankle brachial index (ABI) level and subsequent onset of severe disability. Prospective cohort study. Baltimore community. Eight hundred forty-seven disabled women aged 65 and older participating in the Women's Health and Aging Study. At baseline, participants underwent measurement of ABI and lower extremity functioning. Measures of lower extremity functioning included patient's report of their ability to walk one-quarter of a mile, number of city blocks walked last week, number of stair flights climbed last week, and performance-based measures including walking speed over 4 meters, five repeated chair stands, and a summary performance score. Functioning was remeasured every 6 months for 3 years. Definitions of severe disability were developed a priori, and participants who met these definitions at baseline were excluded from subsequent analyses. Participants with an ABI of less than 0.60 at baseline had significantly higher cumulative probabilities of developing severe disability than participants with a baseline ABI of 0.90 to 1.50 for walking-specific outcomes (ability to walk a quarter of a mile, number of city blocks walked last week, and walking velocity) but not for the remaining functional outcomes. In age-adjusted Cox proportional hazards analyses, hazard ratios for participants with a baseline ABI of less than 0.60 were 1.63 for becoming unable to walk a quarter of a mile (P = .044), 2.00 for developing severe disability in the number of blocks walked last week (P = .004), and 1.61 for developing severe disability in walking speed (P = .041), compared with participants with a baseline ABI of 0.90 to 1.50. Adjusting for age, race, baseline performance, and comorbidities, an ABI of less than 0.60 remained associated with becoming severely disabled in the number of blocks walked last week (hazard ratio = 1.97, P = .009) and nearly significantly associated with becoming unable to walk a quarter of a mile (hazard ratio = 1.54, P = .09). In fully adjusted random effects models, a baseline ABI of less than 0.60 was associated with significantly greater decline in walking speed per year (P = .019) and nearly significantly greater decline in number of blocks walked last week per year (P = .053) compared with a baseline ABI of 0.90 to 1.50. In community-dwelling disabled older women, a low ABI is associated with a greater incidence of severe disability in walking-specific but not other lower extremity functional outcomes, compared with persons with a normal ABI over 3 years.
Semi-parametric regression model for survival data: graphical visualization with R
2016-01-01
Cox proportional hazards model is a semi-parametric model that leaves its baseline hazard function unspecified. The rationale to use Cox proportional hazards model is that (I) the underlying form of hazard function is stringent and unrealistic, and (II) researchers are only interested in estimation of how the hazard changes with covariate (relative hazard). Cox regression model can be easily fit with coxph() function in survival package. Stratified Cox model may be used for covariate that violates the proportional hazards assumption. The relative importance of covariates in population can be examined with the rankhazard package in R. Hazard ratio curves for continuous covariates can be visualized using smoothHR package. This curve helps to better understand the effects that each continuous covariate has on the outcome. Population attributable fraction is a classic quantity in epidemiology to evaluate the impact of risk factor on the occurrence of event in the population. In survival analysis, the adjusted/unadjusted attributable fraction can be plotted against survival time to obtain attributable fraction function. PMID:28090517
Sun, Jianguo; Feng, Yanqin; Zhao, Hui
2015-01-01
Interval-censored failure time data occur in many fields including epidemiological and medical studies as well as financial and sociological studies, and many authors have investigated their analysis (Sun, The statistical analysis of interval-censored failure time data, 2006; Zhang, Stat Modeling 9:321-343, 2009). In particular, a number of procedures have been developed for regression analysis of interval-censored data arising from the proportional hazards model (Finkelstein, Biometrics 42:845-854, 1986; Huang, Ann Stat 24:540-568, 1996; Pan, Biometrics 56:199-203, 2000). For most of these procedures, however, one drawback is that they involve estimation of both regression parameters and baseline cumulative hazard function. In this paper, we propose two simple estimation approaches that do not need estimation of the baseline cumulative hazard function. The asymptotic properties of the resulting estimates are given, and an extensive simulation study is conducted and indicates that they work well for practical situations.
Wang, Wei; Albert, Jeffrey M
2017-08-01
An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.
Joeng, Hee-Koung; Chen, Ming-Hui; Kang, Sangwook
2015-01-01
Discrete survival data are routinely encountered in many fields of study including behavior science, economics, epidemiology, medicine, and social science. In this paper, we develop a class of proportional exponentiated link transformed hazards (ELTH) models. We carry out a detailed examination of the role of links in fitting discrete survival data and estimating regression coefficients. Several interesting results are established regarding the choice of links and baseline hazards. We also characterize the conditions for improper survival functions and the conditions for existence of the maximum likelihood estimates under the proposed ELTH models. An extensive simulation study is conducted to examine the empirical performance of the parameter estimates under the Cox proportional hazards model by treating discrete survival times as continuous survival times, and the model comparison criteria, AIC and BIC, in determining links and baseline hazards. A SEER breast cancer dataset is analyzed in details to further demonstrate the proposed methodology. PMID:25772374
A general framework for parametric survival analysis.
Crowther, Michael J; Lambert, Paul C
2014-12-30
Parametric survival models are being increasingly used as an alternative to the Cox model in biomedical research. Through direct modelling of the baseline hazard function, we can gain greater understanding of the risk profile of patients over time, obtaining absolute measures of risk. Commonly used parametric survival models, such as the Weibull, make restrictive assumptions of the baseline hazard function, such as monotonicity, which is often violated in clinical datasets. In this article, we extend the general framework of parametric survival models proposed by Crowther and Lambert (Journal of Statistical Software 53:12, 2013), to incorporate relative survival, and robust and cluster robust standard errors. We describe the general framework through three applications to clinical datasets, in particular, illustrating the use of restricted cubic splines, modelled on the log hazard scale, to provide a highly flexible survival modelling framework. Through the use of restricted cubic splines, we can derive the cumulative hazard function analytically beyond the boundary knots, resulting in a combined analytic/numerical approach, which substantially improves the estimation process compared with only using numerical integration. User-friendly Stata software is provided, which significantly extends parametric survival models available in standard software. Copyright © 2014 John Wiley & Sons, Ltd.
2013-01-01
Background An inverse relationship between experience and risk of injury has been observed in many occupations. Due to statistical challenges, however, it has been difficult to characterize the role of experience on the hazard of injury. In particular, because the time observed up to injury is equivalent to the amount of experience accumulated, the baseline hazard of injury becomes the main parameter of interest, excluding Cox proportional hazards models as applicable methods for consideration. Methods Using a data set of 81,301 hourly production workers of a global aluminum company at 207 US facilities, we compared competing parametric models for the baseline hazard to assess whether experience affected the hazard of injury at hire and after later job changes. Specific models considered included the exponential, Weibull, and two (a hypothesis-driven and a data-driven) two-piece exponential models to formally test the null hypothesis that experience does not impact the hazard of injury. Results We highlighted the advantages of our comparative approach and the interpretability of our selected model: a two-piece exponential model that allowed the baseline hazard of injury to change with experience. Our findings suggested a 30% increase in the hazard in the first year after job initiation and/or change. Conclusions Piecewise exponential models may be particularly useful in modeling risk of injury as a function of experience and have the additional benefit of interpretability over other similarly flexible models. PMID:23841648
Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya
2018-05-30
Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.
Bancks, Michael P; Alonso, Alvaro; Gottesman, Rebecca F; Mosley, Thomas H; Selvin, Elizabeth; Pankow, James S
2017-12-01
Diabetes is prospectively associated with cognitive decline. Whether lower cognitive function and worse brain structure are prospectively associated with incident diabetes is unclear. We analyzed data for 10,133 individuals with cognitive function testing (1990-1992) and 1212 individuals with brain magnetic resonance imaging (1993-1994) from the Atherosclerosis Risk in Communities cohort. We estimated hazard ratios for incident diabetes through 2014 after adjustment for traditional diabetes risk factors and cohort attrition. Higher level of baseline cognitive function was associated with lower risk for diabetes (per 1 standard deviation, hazard ratio = 0.94; 95% confidence interval = 0.90, 0.98). This association did not persist after accounting for baseline glucose level, case ascertainment methods, and cohort attrition. No association was observed between any brain magnetic resonance imaging measure and incident diabetes. This is one of the first studies to prospectively evaluate the association between both cognitive function and brain structure and the incidence of diabetes. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Lin, Feng-Chang; Zhu, Jun
2012-01-01
We develop continuous-time models for the analysis of environmental or ecological monitoring data such that subjects are observed at multiple monitoring time points across space. Of particular interest are additive hazards regression models where the baseline hazard function can take on flexible forms. We consider time-varying covariates and take into account spatial dependence via autoregression in space and time. We develop statistical inference for the regression coefficients via partial likelihood. Asymptotic properties, including consistency and asymptotic normality, are established for parameter estimates under suitable regularity conditions. Feasible algorithms utilizing existing statistical software packages are developed for computation. We also consider a simpler additive hazards model with homogeneous baseline hazard and develop hypothesis testing for homogeneity. A simulation study demonstrates that the statistical inference using partial likelihood has sound finite-sample properties and offers a viable alternative to maximum likelihood estimation. For illustration, we analyze data from an ecological study that monitors bark beetle colonization of red pines in a plantation of Wisconsin.
Hanley, James A
2008-01-01
Most survival analysis textbooks explain how the hazard ratio parameters in Cox's life table regression model are estimated. Fewer explain how the components of the nonparametric baseline survivor function are derived. Those that do often relegate the explanation to an "advanced" section and merely present the components as algebraic or iterative solutions to estimating equations. None comment on the structure of these estimators. This note brings out a heuristic representation that may help to de-mystify the structure.
A baseline-free procedure for transformation models under interval censorship.
Gu, Ming Gao; Sun, Liuquan; Zuo, Guoxin
2005-12-01
An important property of Cox regression model is that the estimation of regression parameters using the partial likelihood procedure does not depend on its baseline survival function. We call such a procedure baseline-free. Using marginal likelihood, we show that an baseline-free procedure can be derived for a class of general transformation models under interval censoring framework. The baseline-free procedure results a simplified and stable computation algorithm for some complicated and important semiparametric models, such as frailty models and heteroscedastic hazard/rank regression models, where the estimation procedures so far available involve estimation of the infinite dimensional baseline function. A detailed computational algorithm using Markov Chain Monte Carlo stochastic approximation is presented. The proposed procedure is demonstrated through extensive simulation studies, showing the validity of asymptotic consistency and normality. We also illustrate the procedure with a real data set from a study of breast cancer. A heuristic argument showing that the score function is a mean zero martingale is provided.
Modeling Rabbit Responses to Single and Multiple Aerosol ...
Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev
Ng, S K; McLachlan, G J
2003-04-15
We consider a mixture model approach to the regression analysis of competing-risks data. Attention is focused on inference concerning the effects of factors on both the probability of occurrence and the hazard rate conditional on each of the failure types. These two quantities are specified in the mixture model using the logistic model and the proportional hazards model, respectively. We propose a semi-parametric mixture method to estimate the logistic and regression coefficients jointly, whereby the component-baseline hazard functions are completely unspecified. Estimation is based on maximum likelihood on the basis of the full likelihood, implemented via an expectation-conditional maximization (ECM) algorithm. Simulation studies are performed to compare the performance of the proposed semi-parametric method with a fully parametric mixture approach. The results show that when the component-baseline hazard is monotonic increasing, the semi-parametric and fully parametric mixture approaches are comparable for mildly and moderately censored samples. When the component-baseline hazard is not monotonic increasing, the semi-parametric method consistently provides less biased estimates than a fully parametric approach and is comparable in efficiency in the estimation of the parameters for all levels of censoring. The methods are illustrated using a real data set of prostate cancer patients treated with different dosages of the drug diethylstilbestrol. Copyright 2003 John Wiley & Sons, Ltd.
Comparison of methods for estimating the attributable risk in the context of survival analysis.
Gassama, Malamine; Bénichou, Jacques; Dartois, Laureen; Thiébaut, Anne C M
2017-01-23
The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points. Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort. In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears appropriate.
Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D
2017-11-01
Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.
Habibi, Mohammadali; Samiei, Sanaz; Ambale Venkatesh, Bharath; Opdahl, Anders; Helle-Valle, Thomas M; Zareian, Mytra; Almeida, Andre L C; Choi, Eui-Young; Wu, Colin; Alonso, Alvaro; Heckbert, Susan R; Bluemke, David A; Lima, João A C
2016-08-01
Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development. © 2016 American Heart Association, Inc.
Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R
2016-02-01
Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Change in motor function and adverse health outcomes in older African-Americans.
Buchman, Aron S; Wilson, Robert S; Leurgans, Sue E; Bennett, David A; Barnes, Lisa L
2015-10-01
We tested whether declining motor function accelerates with age in older African-Americans. Eleven motor performances were assessed annually in 513 older African-Americans. During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/year (Estimate, -0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p's<0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African-Americans. Copyright © 2015 Elsevier Inc. All rights reserved.
Change in Motor Function and Adverse Health Outcomes in Older African Americas
Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.; Barnes, Lisa L.
2015-01-01
Objective We tested whether declining motor function accelerates with age in older African Americans. Methods Eleven motor performances were assessed annually in 513 older African Americans. Results During follow-up of 5 years, linear mixed-effect models showed that motor function declined by about 0.03 units/yr (Estimate, −0.026, p<0.001); about 4% more rapidly for each additional year of age at baseline. A proportional hazard model showed that both baseline motor function level and its rate of change were independent predictors of death and incident disability (all p’s <0.001). These models showed that the additional annual amount of motor decline in 85 year old persons at baseline versus 65 year old persons was associated with a 1.5-fold higher rate of death and a 3-fold higher rate of developing Katz disability. Conclusions The rate of declining motor function accelerates with increasing age and its rate of decline predicts adverse health outcomes in older African Americans. PMID:26209439
Epstein, Noam U; Guo, Rong; Farlow, Martin R; Singh, Jaswinder P; Fisher, Morris
2014-02-01
Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications, which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer's disease (AD) patients and association with falls is limited. We examined the association between falls and medication use in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in the ADNI, including healthy controls and subjects with mild cognitive impairment or Alzheimer's. Reports detailing adverse event falls were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of the first fall. Age (p < 0.0001), Functional Activities Questionnaire (p = 0.035), Beers List (p = 0.0477) and medications for treating cognitive symptoms of Alzheimer's (p = 0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer's medication use (p = 0.0005) was associated with hazard of fall. Medication was changed by the clinician after an adverse fall event in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. We found a significant association between the use of symptomatic medication treating cognitive symptoms in AD and hazard of fall after adjusting for age and Beers List medication use. Additional pharmacovigilance of the association between falls and Alzheimer's medication use is warranted.
Epstein, Noam U.; Guo, Rong; Farlow, Martin R.; Singh, Jaswinder P.; Fisher, Morris
2014-01-01
Background Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer’s patients and association with falls is limited. Objective We examined the association between falls and medication use in the Alzheimer’s Disease Neuro-Imaging Initiative (ADNI). Methods Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in ADNI including healthy controls and subjects with mild cognitive impairment or Alzheimer’s. Adverse event fall reports were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of first fall. Results Age (p<0.0001), functional activities questionnaire (p=0.035), Beers list (p=0.0477) and medications for treating cognitive symptoms of Alzheimer’s (p=0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer’s medication use (p=0.0005) was associated with hazard of fall. Medication was changed after an adverse fall event by the clinician in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. Conclusion We found a significant association between use of symptomatic medication treating cognitive symptoms in Alzheimer’s disease and hazard of fall after adjusting for age and Beers list medication use. Additional pharmaco-vigilance of the association between falls and Alzheimer’s medication use is warranted. PMID:24357133
Katz, Ronit; Dalrymple, Lorien; de Boer, Ian; DeFilippi, Christopher; Kestenbaum, Bryan; Park, Meyeon; Sarnak, Mark; Seliger, Stephen; Shlipak, Michael
2015-01-01
Background and objectives Elevations in N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated. Design, setting, participants, & measurements N-terminal pro–B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors. Results In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro–B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50). Conclusions Elevated N-terminal pro–B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association. PMID:25605700
Cox Regression Models with Functional Covariates for Survival Data.
Gellar, Jonathan E; Colantuoni, Elizabeth; Needham, Dale M; Crainiceanu, Ciprian M
2015-06-01
We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge and daily measures of disease severity collected in the intensive care unit, among survivors of acute respiratory distress syndrome.
Fredman, Lisa; Lyons, Jennifer G; Cauley, Jane A; Hochberg, Marc; Applebaum, Katie M
2015-09-01
Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62-0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38-0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52-0.88, 5-year lag hazard ratios = 0.76, 0.60-0.95). Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Kidane, Biniam; Sulman, Joanne; Xu, Wei; Kong, Qin Quinn; Wong, Rebecca; Knox, Jennifer J; Darling, Gail E
2016-06-01
Functional Assessment of Cancer Therapy-Esophagus is a health-related quality of life instrument validated in patients with esophageal cancer. It is composed of a general component and an esophageal cancer subscale. Our objective was to determine whether the baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores are associated with survival in patients with stage II and III cancer of the gastroesophageal junction or thoracic esophagus. Data from 4 prospective studies in Canadian academic hospitals were combined. These included consecutive patients with stage II and III esophageal cancer who received neoadjuvant therapy followed by surgery or chemoradiation/radiation alone. All patients completed baseline Functional Assessment of Cancer Therapy-Esophagus. Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores were dichotomized on the basis of median scores. Cox regression analyses were performed. There were 207 patients treated between 1996 and 2014. Mean age was 61 ± 10.6 years. Approximately 69.6% of patients (n = 144) had adenocarcinoma. All patients had more than 9 months of follow-up. In patients with stage II and III, 93 deaths were observed. When treated as continuous variables, baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were associated with survival with hazard ratios of 0.89 (95% confidence interval [CI], 0.81-0.96; P = .005) and 0.68 (95% CI, 0.56-0.82; P < .001), respectively. When dichotomized, they were also associated with survival with a hazard ratio of 0.58 (95% CI, 0.38-0.89; P = .01) and 0.43 (95% CI, 0.28-0.67; P < .001), respectively. In patients with stage II and III esophageal cancer being considered for therapy, higher baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were independently associated with longer survival, even after adjusting for age, stage, histology, and therapy received. Further study is needed, but Functional Assessment of Cancer Therapy-Esophagus may be useful as a prognostic tool to inform patient decision-making and patient selection criteria for studies. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Renal Function Changes Following Left Ventricular Assist Device Implantation.
Daimee, Usama A; Wang, Meng; Papernov, Anna; Sherazi, Saadia; McNitt, Scott; Vidula, Himabindu; Chen, Leway; Alexis, Jeffrey D; Kutyifa, Valentina
2017-12-15
Limited data assessing the clinical significance of post-left ventricular assist device (LVAD) in renal function are available. We aimed to investigate the impact of changes in renal function after LVAD implantation on subsequent long-term outcomes. We followed 184 patients with HeartMate II LVADs implanted between May 2008 and November 2014. Serial assessment of renal function, was performed at baseline and at day 1, day 7, 1 month, 3 months, 6 months, 1 year, and 2 years after implantation. Effects of 1-month GFR and changes in GFR from baseline to 1 month on long-term mortality and hospital re-admission were evaluated. There were 30 patients with GFR <45 (low), 44 with GFR 45 to 59 (intermediate), and 110 with GFR ≥60 (normal) at baseline. Only patients with baseline GFR <45 experienced significant improvement in GFR after 2 years of follow-up (p = 0.012). At 1 month, a higher GFR category was significantly associated with a 31% reduction in mortality (hazard ratio [HR] 0.69, CI 0.49 to 0.98, p = 0.036), but not re-admission. Patients with baseline low and intermediate GFR who had no improvement in renal function category at 1 month experienced significantly greater risk of mortality (HR 1.95, CI 1.10 to 3.43, p = 0.022) and re-admission (HR 1.75, CI 1.07 to 2.84, p = 0.025), relative to patients whose GFR was normal at baseline and 1 month. In conclusion, renal function after LVAD implantation improves in patients with GFR <45. Change in renal function from baseline to 1 month after implantation is a powerful marker of long-term outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
Lanfear, David E; Peterson, Edward L; Campbell, Janis; Phatak, Hemant; Wu, David; Wells, Karen; Spertus, John A; Williams, L Keoki
2011-01-01
Worsened renal function (WRF) during heart failure (HF) hospitalization is associated with in-hospital mortality, but there are limited data regarding its relation to long-term outcomes after discharge. The influence of WRF resolution is also unknown. This retrospective study analyzed patients who received care from a large health system and had a primary hospital discharge diagnosis of HF from January 2000 to June 2008. Renal function was estimated from creatinine levels during hospitalization. The first available value was considered baseline. WRF was defined a creatinine increase ≥ 0.3 mg/dl on any subsequent hospital day compared to baseline. Persistent WRF was defined as having WRF at discharge. Proportional hazards regression, adjusting for baseline renal function and potential confounding factors, was used to assess time to rehospitalization or death. Of 2,465 patients who survived to discharge, 887 (36%) developed WRF. Median follow-up was 2.1 years. In adjusted models, WRF was associated with higher rates of postdischarge death or rehospitalization (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02 to 1.22). Of those with WRF, 528 (60%) had persistent WRF, whereas 359 (40%) recovered. Persistent WRF was significantly associated with higher postdischarge event rates (HR 1.14, 95% CI 1.02 to 1.27), whereas transient WRF showed only a nonsignificant trend toward risk (HR 1.09, 95% CI 0.96 to 1.24). In conclusion, in patients surviving hospitalization for HF, WRF was associated with increased long-term mortality and rehospitalization, particularly if renal function did not recover by the time of discharge. Copyright © 2011 Elsevier Inc. All rights reserved.
A method for analyzing clustered interval-censored data based on Cox's model.
Kor, Chew-Teng; Cheng, Kuang-Fu; Chen, Yi-Hau
2013-02-28
Methods for analyzing interval-censored data are well established. Unfortunately, these methods are inappropriate for the studies with correlated data. In this paper, we focus on developing a method for analyzing clustered interval-censored data. Our method is based on Cox's proportional hazard model with piecewise-constant baseline hazard function. The correlation structure of the data can be modeled by using Clayton's copula or independence model with proper adjustment in the covariance estimation. We establish estimating equations for the regression parameters and baseline hazards (and a parameter in copula) simultaneously. Simulation results confirm that the point estimators follow a multivariate normal distribution, and our proposed variance estimations are reliable. In particular, we found that the approach with independence model worked well even when the true correlation model was derived from Clayton's copula. We applied our method to a family-based cohort study of pandemic H1N1 influenza in Taiwan during 2009-2010. Using the proposed method, we investigate the impact of vaccination and family contacts on the incidence of pH1N1 influenza. Copyright © 2012 John Wiley & Sons, Ltd.
TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects.
Jun, Ji Eun; Jin, Sang-Man; Jee, Jae Hwan; Bae, Ji Cheol; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Sun Wook; Kim, Jae Hyeon
2017-03-01
Thyroid function is known to influence glucose metabolism, and thyroid-stimulating hormone is the most useful parameter in screening for thyroid dysfunction. Therefore, the aim of this study was to investigate the incidence of type 2 diabetes according to baseline thyroid-stimulating hormone level and thyroid-stimulating hormone change in euthyroid subjects. We identified and enrolled 17,061 euthyroid subjects without diabetes among participants who had undergone consecutive thyroid function tests between 2006 and 2012 as a part of yearly health check-up program. Thyroid-stimulating hormone changes were determined by subtracting baseline thyroid-stimulating hormone level from thyroid-stimulating hormone level at 1 year before diagnosis of diabetes or at the end of follow-up in subjects who did not develope diabetes. During 84,595 person-years of follow-up, there were 956 new cases of type 2 diabetes. Cox proportional hazards models showed the risk of incident type 2 diabetes was significantly increased with each 1 μIU/mL increment in TSH after adjustment for multiple confounding factors (hazard ratio = 1.13, 95% confidence interval: 1.07-1.20, P < 0.001). Compared with individuals in the lowest tertile (-4.08 to 0.34 μIU/mL), those in the highest thyroid-stimulating hormone change tertile (0.41-10.84 μIU/mL) were at greater risk for incident type 2 diabetes (hazard ratio = 1.25, 95% confidence interval: 1.05-1.48, P for trend = 0.011). However, baseline thyroid-stimulating hormone level and tertile were not associated with the risk for diabetes. Prominent increase in thyroid-stimulating hormone concentration can be an additional risk factor for the development of type 2 diabetes in euthyroid subjects.
Outcome of intracerebral hemorrhage associated with different oral anticoagulants
Wilson, Duncan; Seiffge, David J.; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C.; Rizos, Timolaos; Sobowale, Oluwaseun A.; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y.; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H.B.M.; Perry, Luke A.; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R.; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M.C.; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T.; Parry-Jones, Adrian R.; Meretoja, Atte
2017-01-01
Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH). Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]). Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. PMID:28381513
Outcome of intracerebral hemorrhage associated with different oral anticoagulants.
Wilson, Duncan; Seiffge, David J; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C; Rizos, Timolaos; Sobowale, Oluwaseun A; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H B M; Perry, Luke A; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M C; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T; Parry-Jones, Adrian R; Meretoja, Atte; Werring, David J
2017-05-02
In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH ( p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [ p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [ p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [ p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [ p = 0.11]). In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
A 10-Year Follow-Up Study of Social Ties and Functional Health among the Old: The AGES Project
Murata, Chiyoe; Saito, Tami; Tsuji, Taishi; Saito, Masashige
2017-01-01
In Asian nations, family ties are considered important. However, it is not clear what happens among older people with no such ties. To investigate the association, we used longitudinal data from the Aichi Gerontological Evaluation Study (AGES) project. Functionally independent older people at baseline (N = 14,088) in 10 municipalities were followed from 2003 to 2013. Social ties were assessed by asking about their social support exchange with family, relatives, friends, or neighbors. Cox proportional hazard models were employed to investigate the association between social ties and the onset of functional disability adjusting for age, health status, and living arrangement. We found that social ties with co-residing family members, and those with friends or neighbors, independently protected functional health with hazard ratios of 0.81 and 0.85 among men. Among women, ties with friend or neighbors had a stronger effect on health compared to their male counterparts with a hazard ratio of 0.89. The fact that social ties with friends or neighbors are associated with a lower risk of functional decline, independent of family support, serves to underscore the importance of promoting social ties, especially among those lacking family ties. PMID:28671627
The association between mental health, physical function, and hemodialysis mortality.
Knight, Eric L; Ofsthun, Norma; Teng, Ming; Lazarus, J Michael; Curhan, Gary C
2003-05-01
Mortality rates for individuals on chronic hemodialysis remain very high; therefore, strategies are needed to identify individuals at greatest risk for mortality so preventive strategies can be implemented. One such approach is to stratify individuals by self-reported mental health and physical function. Examining these parameters at baseline, and over time, may help identify individuals at greater risk for mortality. We enrolled 14,815 individuals with end-stage renal disease (ESRD) and followed these individuals for up to 2 years. The mean age was 61.0 +/- 15.4 years (range, 20 to 96 years) and 31% were African Americans. The SF-36 Health Survey was administered 1 to 3 months after hemodialysis initiation and 6 months later. We examined the associations between the initial SF-36 Health Survey mental component summary (MCS) and physical component summary (PCS) scores and mortality during the follow-up period, and examined the associations between 6-month decline in PCS and MCS scores and subsequent mortality. We also examined the interactions between age and MCS and PCS scores. The general population-based mean of each of these scores was 50 with a standard deviation of 10. The main outcome measurement was death. Self-reported baseline mental health (MCS score) and physical function (PCS score) were both independently associated with increased mortality, and 6-month decline in these parameters was also associated with increased mortality. The multivariate hazard ratios for 1-year mortality for MCS scores of less than 30, 30 to 39, and 40 to 49 were 1.48 (95% CI, 1.32 to 1.64), 1.23 (95% CI, 1.14 to 1.32) and 1.18 (95% CI, 1.10 to 1.26) compared with a MCS score of 50 or more. The hazard ratios for PCS scores of less than 20, 20 to 29, and 30 to 39 were 1.97 (95% CI, 1.64 to 2.36), 1.62 (95% CI, 1.36 to 1.92), and 1.32 (95% CI, 1.11 to 1.57) compared with a PCS score of 50 or more. Six-month decline in self-reported mental health (hazard ratio, 1.07; 95% CI, 1.02 to 1.12, per 10-point decline in MCS score) and physical function (hazard ratio, 1.25; 95% CI, 1.18 to 1.33, per 10-point decline in PCS score) were also both significantly associated with an additional increase in mortality beyond baseline risk. We also found a significant interaction between age and physical function (P = 0.02). Specifically, there was a graded response between the PCS score category and mortality in most age strata, but this relationship was not observed in the oldest age (85 years old or older). In individuals newly initiated on chronic hemodialysis, self-reported baseline mental health and physical function are important, independent predictors of mortality, and there is a graded relationship between these parameters and mortality risk. Following these parameters over time provides additional information on mortality risk. One must also consider age when interpreting the relationship between physical function and mortality.
Validation of a heteroscedastic hazards regression model.
Wu, Hong-Dar Isaac; Hsieh, Fushing; Chen, Chen-Hsin
2002-03-01
A Cox-type regression model accommodating heteroscedasticity, with a power factor of the baseline cumulative hazard, is investigated for analyzing data with crossing hazards behavior. Since the approach of partial likelihood cannot eliminate the baseline hazard, an overidentified estimating equation (OEE) approach is introduced in the estimation procedure. It by-product, a model checking statistic, is presented to test for the overall adequacy of the heteroscedastic model. Further, under the heteroscedastic model setting, we propose two statistics to test the proportional hazards assumption. Implementation of this model is illustrated in a data analysis of a cancer clinical trial.
Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon
2015-11-01
To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.
Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease
Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon
2015-01-01
Abstract To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD). Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline. After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97–1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88–0.99). The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD. PMID:26559259
van der Velde, A Rogier; Gullestad, Lars; Ueland, Thor; Aukrust, Pål; Guo, Yu; Adourian, Aram; Muntendam, Pieter; van Veldhuisen, Dirk J; de Boer, Rudolf A
2013-03-01
In several cross-sectional analyses, circulating baseline levels of galectin-3, a protein involved in myocardial fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with heart failure (HF). The importance and clinical use of repeated measurements of galectin-3 have not yet been reported. Plasma galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324). Patient results were analyzed by categorical and percentage changes in galectin-3 level. A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients. Increasing galectin-3 levels over time, from a low to high galectin-3 category, were associated with significantly more HF hospitalization and mortality compared with stable or decreasing galectin-3 levels (hazard ratio in CORONA, 1.60; 95% confidence interval, 1.13-2.25; P=0.007; hazard ratio in COACH, 2.38; 95% confidence interval, 1.02-5.55; P=0.046). In addition, patients whose galectin-3 increased by >15% between measurements had a 50% higher relative hazard of adverse event than those whose galectin-3 stayed within ±15% of the baseline value, independent of age, sex, diabetes mellitus, left ventricular ejection fraction, renal function, medication (β-blocker, angiotensin converting enzyme inhibitor, and angiotensin receptor blocker), and N-terminal probrain natriuretic peptide (hazard ratio in CORONA, 1.50; 95% confidence interval, 1.17-1.92; P=0.001). The impact of changing galectin-3 levels on other secondary end points was comparable. In 2 large cohorts of patients with chronic and acute decompensated HF, repeated measurements of galectin-3 level provided important and significant prognostic value in identifying patients with HF at elevated risk for subsequent HF morbidity and mortality.
Clarke, Megan M; Dorsch, Michael P; Kim, Susie; Aaronson, Keith D; Koelling, Todd M; Bleske, Barry E
2013-06-01
To identify baseline predictors of worsening renal function (WRF) in an acute decompensated heart failure (ADHF) patient population receiving continuous infusion loop diuretics. Retrospective observational analysis. Academic tertiary medical center. A total of 177 patients with ADHF receiving continuous infusion loop diuretics from January 2006 through June 2009. The mean patient age was 61 years, 63% were male, ~45% were classified as New York Heart Association functional class III, and the median length of loop diuretic infusion was 4 days. Forty-eight patients (27%) developed WRF, and 34 patients (19%) died during hospitalization. Cox regression time-to-event analysis was used to determine the time to WRF based on different demographic and clinical variables. Baseline serum albumin 3 g/dl or less was the only significant predictor of WRF (hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.60-5.16, p=0.0004), which remained significant despite adjustments for other covariates. Serum albumin 3 g/dl or less is a practical baseline characteristic associated with the development of WRF in patients with ADHF receiving continuous infusion loop diuretics. © 2013 Pharmacotherapy Publications, Inc.
Navarro, Albert; Casanovas, Georgina; Alvarado, Sergio; Moriña, David
Researchers in public health are often interested in examining the effect of several exposures on the incidence of a recurrent event. The aim of the present study is to assess how well the common-baseline hazard models perform to estimate the effect of multiple exposures on the hazard of presenting an episode of a recurrent event, in presence of event dependence and when the history of prior-episodes is unknown or is not taken into account. Through a comprehensive simulation study, using specific-baseline hazard models as the reference, we evaluate the performance of common-baseline hazard models by means of several criteria: bias, mean squared error, coverage, confidence intervals mean length and compliance with the assumption of proportional hazards. Results indicate that the bias worsen as event dependence increases, leading to a considerable overestimation of the exposure effect; coverage levels and compliance with the proportional hazards assumption are low or extremely low, worsening with increasing event dependence, effects to be estimated, and sample sizes. Common-baseline hazard models cannot be recommended when we analyse recurrent events in the presence of event dependence. It is important to have access to the history of prior-episodes per subject, it can permit to obtain better estimations of the effects of the exposures. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.
Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A
2017-07-07
Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.
Motor Function Is Associated With Incident Disability in Older African Americans
Wilson, Robert S.; Yu, Lei; Boyle, Patricia A.; Bennett, David A.; Barnes, Lisa L.
2016-01-01
Background: Disability in older African American adults is common, but its basis is unclear. We tested the hypothesis that the level of motor function is associated with incident disability in older African Americans after adjusting for cognition. Methods: A prospective observational cohort study of 605 older community-dwelling African American adults without dementia was carried out. Baseline global motor score summarized 11 motor performances, cognition was based on 19 cognitive tests, and self-reported disability was obtained annually. We examined the association of motor function with incident disability (instrumental activities of daily living [IADL], activities of daily living [ADL], and mobility disability) with a series of Cox proportional hazards models which controlled for age, sex, and education. Results: Average follow-up was about 5 years. In proportional hazards models, a 1-SD increase in baseline level of global motor score was associated with about a 50% decrease in the risk of subsequent IADL, ADL, and mobility disability (all p values < .001). These associations were unchanged in analyses controlling for cognition and other covariates. Further, the association of global motor score and incident ADL disability varied with the level of cognition (estimate −5.541, SE 1.634, p < .001), such that higher motor function was more protective at higher levels of cognition. Mobility and dexterity components of global motor score were more strongly associated with incident disability than strength (all p values < .001). Conclusions: Better motor function in older African Americans is associated with a decreased risk of developing disability. Moreover, the association of motor function and disability is stronger in individuals with better cognitive function. PMID:26525087
Jensen, Annette S; Broberg, Craig S; Rydman, Riikka; Diller, Gerhard-Paul; Li, Wei; Dimopoulos, Konstantinos; Wort, Stephen J; Pennell, Dudley J; Gatzoulis, Michael A; Babu-Narayan, Sonya V
2015-12-01
Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up. © 2015 American Heart Association, Inc.
Association between late-life social activity and motor decline in older adults.
Buchman, Aron S; Boyle, Patricia A; Wilson, Robert S; Fleischman, Debra A; Leurgans, Sue; Bennett, David A
2009-06-22
Loss of motor function is a common consequence of aging, but little is known about the factors that predict idiopathic motor decline. Our objective was to test the hypothesis that late-life social activity is related to the rate of change in motor function in old age. Longitudinal cohort study with a mean follow-up of 4.9 years with 906 persons without stroke, Parkinson disease, or dementia participating in the Rush Memory and Aging Project. At baseline, participants rated the frequency of their current participation in common social activities from which a summary measure of social activity was derived. The main outcome measure was annual change in a composite measure of global motor function, based on 9 measures of muscle strength and 9 motor performances. Mean (SD) social activity score at baseline was 2.6 (0.58), with higher scores indicating more frequent participation in social activities. In a generalized estimating equation model, controlling for age, sex, and education, global motor function declined by approximately 0.05 U/y (estimate, 0.016; 95% confidence interval [CI], -0.057 to 0.041 [P = .02]). Each 1-point decrease in social activity was associated with approximately a 33% more rapid rate of decline in motor function (estimate, 0.016; 95% CI, 0.003 to 0.029 [P = .02]). The effect of each 1-point decrease in the social activity score at baseline on the rate of change in global motor function was the same as being approximately 5 years older at baseline (age estimate, -0.003; 95% CI, -0.004 to -0.002 [P<.001]). Furthermore, this amount of motor decline per year was associated with a more than 40% increased risk of death (hazard ratio, 1.44; 95% CI, 1.30 to 1.60) and a 65% increased risk of incident Katz disability (hazard ratio, 1.65; 95% CI, 1.48 to 1.83). The association of social activity with the rate of global motor decline did not vary along demographic lines and was unchanged (estimate, 0.025; 95% CI, 0.005 to 0.045 [P = .01]) after controlling for potential confounders including late-life physical and cognitive activity, disability, global cognition depressive symptoms, body composition, and chronic medical conditions. Less frequent participation in social activities is associated with a more rapid rate of motor function decline in old age.
2014-01-01
Background Alcohol use has a detrimental impact on the HIV epidemic, especially in sub-Saharan Africa. HIV counseling and testing (HCT) may provide a contact opportunity to intervene with hazardous alcohol use; however, little is known about how alcohol consumption changes following HCT. Methods We utilized data from 2056 participants of a randomized controlled trial comparing two methods of HCT and subsequent linkage to HIV care conducted at Mulago Hospital in Kampala, Uganda. Those who had not previously tested positive for HIV and whose last HIV test was at least one year in the past were eligible. Participants were asked at baseline when they last consumed alcohol, and prior three month alcohol consumption was measured using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) at baseline and quarterly for one year. Hazardous alcohol consumption was defined as scoring ≥3 or ≥4 for women and men, respectively. We examined correlates of alcohol use at baseline, and of hazardous and non-hazardous drinking during the year of follow-up using multinomial logistic regression, clustered at the participant level to account for repeated measurements. Results Prior to HCT, 30% were current drinkers (prior three months), 27% were past drinkers (>3 months ago), and 44% were lifetime abstainers. One-third (35%) of the current drinkers met criteria for hazardous drinking. Hazardous and non-hazardous self-reported alcohol consumption declined after HCT, with 16% of baseline current drinkers reporting hazardous alcohol use 3 months after HCT. Independent predictors (p < 0.05) of continuing non-hazardous and hazardous alcohol consumption after HCT were sex (male), alcohol consumption prior to HCT (hazardous), and HIV status (negative). Among those with HIV, non-hazardous drinking was less likely among those taking antiretroviral therapy (ART). Conclusions HCT may be an opportune time to intervene with alcohol consumption. Those with HIV experienced greater declines in alcohol consumption after HCT, and non-hazardous drinking decreased for those with HIV initiating ART. HCT and ART initiation may be ideal times to intervene with alcohol consumption. Screening and brief intervention (SBI) to reduce alcohol consumption should be considered for HCT and HIV treatment venues. PMID:25038830
Covariate Measurement Error Correction Methods in Mediation Analysis with Failure Time Data
Zhao, Shanshan
2014-01-01
Summary Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This paper focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error and error associated with temporal variation. The underlying model with the ‘true’ mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling design. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. PMID:25139469
Covariate measurement error correction methods in mediation analysis with failure time data.
Zhao, Shanshan; Prentice, Ross L
2014-12-01
Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. © 2014, The International Biometric Society.
Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction.
Sato, Masaaki; Waddell, Thomas K; Wagnetz, Ute; Roberts, Heidi C; Hwang, David M; Haroon, Ayesha; Wagnetz, Dirk; Chaparro, Cecilia; Singer, Lianne G; Hutcheon, Michael A; Keshavjee, Shaf
2011-07-01
Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated. Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used. Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07). RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Cremer, Paul C; Zhang, Yiran; Alu, Maria; Rodriguez, L Leonardo; Lindman, Brian R; Zajarias, Alan; Hahn, Rebecca T; Lerakis, Stamatios; Malaisrie, S Chris; Douglas, Pamela S; Pibarot, Philippe; Svensson, Lars G; Leon, Martin B; Jaber, Wael A
2018-05-08
In patients randomized to transcatheter or surgical aortic valve replacement (TAVR, SAVR), we sought to determine whether SAVR is associated with worsening right ventricular (RV) function and whether RV deterioration is associated with mortality. In 1376 patients from PARTNERIIA with paired baseline and 30-day core lab echocardiograms, worsening RV function was defined as decline by at least one grade from baseline to 30 days. Our primary outcome was all-cause mortality from 30 days to 2 years. Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) (P < 0.0001). In a multivariable model, SAVR [odds ratio (OR) 4.05, 95% confidence interval (CI) 2.55-6.44], a dilated RV (OR 2.38, 95% CI 1.37-4.14), and more than mild tricuspid regurgitation (TR) (OR 2.58, 95% CI 1.25-5.33) were associated with worsening RV function. There were 169 deaths, and patients with worsening RV function had higher all-cause mortality [hazard ratio (HR) 1.98, 95% CI 1.40-2.79]. This association remained robust after adjusting for clinical and echocardiographic variables. Among patients with worsening RV function, there was no mortality difference between TAVR and SAVR (HR 1.16, 95% CI 0.61-2.18). The development of moderate or severe RV dysfunction from baseline normal RV function conferred the worst prognosis (HR 2.87, 95% CI 1.40-5.89). After aortic valve replacement, worsening RV function is more common in patients with baseline RV dilation, more than mild TR, and in patients treated with SAVR. Worsening RV function and the magnitude of deterioration have important prognostic implications.
Parametric regression model for survival data: Weibull regression model as an example
2016-01-01
Weibull regression model is one of the most popular forms of parametric regression model that it provides estimate of baseline hazard function, as well as coefficients for covariates. Because of technical difficulties, Weibull regression model is seldom used in medical literature as compared to the semi-parametric proportional hazard model. To make clinical investigators familiar with Weibull regression model, this article introduces some basic knowledge on Weibull regression model and then illustrates how to fit the model with R software. The SurvRegCensCov package is useful in converting estimated coefficients to clinical relevant statistics such as hazard ratio (HR) and event time ratio (ETR). Model adequacy can be assessed by inspecting Kaplan-Meier curves stratified by categorical variable. The eha package provides an alternative method to model Weibull regression model. The check.dist() function helps to assess goodness-of-fit of the model. Variable selection is based on the importance of a covariate, which can be tested using anova() function. Alternatively, backward elimination starting from a full model is an efficient way for model development. Visualization of Weibull regression model after model development is interesting that it provides another way to report your findings. PMID:28149846
Maximum Likelihood Estimations and EM Algorithms with Length-biased Data
Qin, Jing; Ning, Jing; Liu, Hao; Shen, Yu
2012-01-01
SUMMARY Length-biased sampling has been well recognized in economics, industrial reliability, etiology applications, epidemiological, genetic and cancer screening studies. Length-biased right-censored data have a unique data structure different from traditional survival data. The nonparametric and semiparametric estimations and inference methods for traditional survival data are not directly applicable for length-biased right-censored data. We propose new expectation-maximization algorithms for estimations based on full likelihoods involving infinite dimensional parameters under three settings for length-biased data: estimating nonparametric distribution function, estimating nonparametric hazard function under an increasing failure rate constraint, and jointly estimating baseline hazards function and the covariate coefficients under the Cox proportional hazards model. Extensive empirical simulation studies show that the maximum likelihood estimators perform well with moderate sample sizes and lead to more efficient estimators compared to the estimating equation approaches. The proposed estimates are also more robust to various right-censoring mechanisms. We prove the strong consistency properties of the estimators, and establish the asymptotic normality of the semi-parametric maximum likelihood estimators under the Cox model using modern empirical processes theory. We apply the proposed methods to a prevalent cohort medical study. Supplemental materials are available online. PMID:22323840
Alashi, Alaa; Mentias, Amgad; Patel, Krishna; Gillinov, A Marc; Sabik, Joseph F; Popović, Zoran B; Mihaljevic, Tomislav; Suri, Rakesh M; Rodriguez, L Leonardo; Svensson, Lars G; Griffin, Brian P; Desai, Milind Y
2016-07-01
In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm(2), 58±13 cc/m(2), and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and -20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (χ(2) for longer-term mortality increased from 31-47 to 61; P<0.001). In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors. © 2016 American Heart Association, Inc.
Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken
2007-07-01
Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.
Log-normal frailty models fitted as Poisson generalized linear mixed models.
Hirsch, Katharina; Wienke, Andreas; Kuss, Oliver
2016-12-01
The equivalence of a survival model with a piecewise constant baseline hazard function and a Poisson regression model has been known since decades. As shown in recent studies, this equivalence carries over to clustered survival data: A frailty model with a log-normal frailty term can be interpreted and estimated as a generalized linear mixed model with a binary response, a Poisson likelihood, and a specific offset. Proceeding this way, statistical theory and software for generalized linear mixed models are readily available for fitting frailty models. This gain in flexibility comes at the small price of (1) having to fix the number of pieces for the baseline hazard in advance and (2) having to "explode" the data set by the number of pieces. In this paper we extend the simulations of former studies by using a more realistic baseline hazard (Gompertz) and by comparing the model under consideration with competing models. Furthermore, the SAS macro %PCFrailty is introduced to apply the Poisson generalized linear mixed approach to frailty models. The simulations show good results for the shared frailty model. Our new %PCFrailty macro provides proper estimates, especially in case of 4 events per piece. The suggested Poisson generalized linear mixed approach for log-normal frailty models based on the %PCFrailty macro provides several advantages in the analysis of clustered survival data with respect to more flexible modelling of fixed and random effects, exact (in the sense of non-approximate) maximum likelihood estimation, and standard errors and different types of confidence intervals for all variance parameters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
National-Level Multi-Hazard Risk Assessments in Sub-Saharan Africa
NASA Astrophysics Data System (ADS)
Murnane, R. J.; Balog, S.; Fraser, S. A.; Jongman, B.; Van Ledden, M.; Phillips, E.; Simpson, A.
2017-12-01
National-level risk assessments can provide important baseline information for decision-making on risk management and risk financing strategies. In this study, multi-hazard risk assessments were undertaken for 9 countries in Sub-Saharan Africa: Cape Verde, Ethiopia, Kenya, Niger, Malawi, Mali, Mozambique, Senegal and Uganda. The assessment was part of the Building Disaster Resilience in Sub-Saharan Africa Program and aimed at supporting the development of multi-risk financing strategies to help African countries make informed decisions to mitigate the socio-economic, fiscal and financial impacts of disasters. The assessments considered hazards and exposures consistent with the years 2010 and 2050. We worked with multiple firms to develop the hazard, exposure and vulnerability data and the risk results. The hazards include: coastal flood, drought, earthquake, landslide, riverine flood, tropical cyclone wind and storm surge, and volcanoes. For hazards expected to vary with climate, the 2050 hazard is based on the IPCC RCP 6.0. Geolocated exposure data for 2010 and 2050 at a 15 arc second ( 0.5 km) resolution includes: structures as a function of seven development patterns; transportation networks including roads, bridges, tunnels and rail; critical facilities such as schools, hospitals, energy facilities and government buildings; crops; population; and, gross domestic product (GDP). The 2050 exposure values for population are based on the IPCC SSP 2. Values for other exposure data are a function of population change. Vulnerability was based on openly available vulnerability functions. Losses were based on replacement values (e.g., cost/m2 or cost/km). Risk results are provided in terms of annual average loss and a variety of return periods at the national and Admin 1 levels. Assessments of recent historical events are used to validate the model results. In the future, it would be useful to use hazard footprints of historical events for validation purposes. The results will be visualized in a set of national risk profile documents intended to form the basis for conversations with governments on risk reduction and risk financing strategies.
Formiga, Francesc; Ferrer, Assumpta; Padros, Gloria; Montero, Abelardo; Gimenez-Argente, Carme; Corbella, Xavier
2016-01-01
Objective To investigate the predictive value of functional impairment, chronic conditions, and laboratory biomarkers of aging for predicting 5-year mortality in the elderly aged 85 years. Methods Predictive value for mortality of different geriatric assessments carried out during the OCTABAIX study was evaluated after 5 years of follow-up in 328 subjects aged 85 years. Measurements included assessment of functional status comorbidity, along with laboratory tests on vitamin D, cholesterol, CD4/CD8 ratio, hemoglobin, and serum thyrotropin. Results Overall, the mortality rate after 5 years of follow-up was 42.07%. Bivariate analysis showed that patients who survived were predominantly female (P=0.02), and they showed a significantly better baseline functional status for both basic (P<0.001) and instrumental (P<0.001) activities of daily living (Barthel and Lawton index), better cognitive performance (Spanish version of the Mini-Mental State Examination) (P<0.001), lower comorbidity conditions (Charlson) (P<0.001), lower nutritional risk (Mini Nutritional Assessment) (P<0.001), lower risk of falls (Tinetti gait scale) (P<0.001), less percentage of heart failure (P=0.03) and chronic obstructive pulmonary disease (P=0.03), and took less chronic prescription drugs (P=0.002) than nonsurvivors. Multivariate Cox regression analysis identified a decreased score in the Lawton index (hazard ratio 0.86, 95% confidence interval: 0.78–0.91) and higher comorbidity conditions (hazard ratio 1.20, 95% confidence interval: 1.08–1.33) as independent predictors of mortality at 5 years in the studied population. Conclusion The ability to perform instrumental activities of daily living and the global comorbidity assessed at baseline were the predictors of death, identified in our 85-year-old community-dwelling subjects after 5 years of follow-up. PMID:27143867
Premorbid functional development and conversion to psychosis in clinical high-risk youths
Tarbox, Sarah I.; Addington, Jean; Cadenhead, Kristin S.; Cannon, Tyrone D.; Cornblatt, Barbara A.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming T.; Walker, Elaine F.; Heinssen, Robert; Mcglashan, Thomas H.; Woods, Scott W.
2014-01-01
Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention. PMID:24229556
Calcaterra, Susan L; Beaty, Brenda; Mueller, Shane R; Min, Sung-Joon; Binswanger, Ingrid A
2014-07-01
Social stressors are associated with relapse to substance use among people receiving addiction treatment and people with substance use risk behaviors. The relationship between social stressors and drug use/hazardous drinking in former prisoners has not been studied. We interviewed former prisoners at baseline, 1 to 3 weeks post prison release, and follow up, between 2 and 9 months following the baseline interview. Social stressors were characterized by unemployment, homelessness, unstable housing, problems with family, friends, and/or significant others, being single, or major symptoms of depression. Associations between baseline social stressors and follow-up drug use and hazardous drinking were analyzed using multivariable logistic regression. Problems with family, friends, and/or significant others were associated with reported drug use (AOR 3.01, 95% CI 1.18-7.67) and hazardous drinking (AOR 2.69, 95% CI 1.05-6.87) post release. Further research may determine whether interventions and policies targeting social stressors can reduce relapse among former inmates. Copyright © 2014 Elsevier Inc. All rights reserved.
Neurobehavioral Functioning and Survival Following Lung Transplantation
Blumenthal, James A.; Carney, Robert M.; Freedland, Kenneth E.; O’Hayer, C. Virginia F.; Trulock, Elbert P.; Martinu, Tereza; Schwartz, Todd A.; Hoffman, Benson M.; Koch, Gary G.; Davis, R. Duane; Palmer, Scott M.
2014-01-01
Background: Neurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients. Methods: The sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments. Results: One hundred eleven patients died over a mean follow-up of 10.8 years (SD = 0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR] = 1.09, P = .012) and memory performance (HR = 1.11, P = .030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored > 13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR = 1.85 [95% CI, 1.04, 3.28], P = .036). Conclusions: Neurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation. Trial registry: ClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov PMID:24233282
Lundin, A; Modig, K; Halldin, J; Carlsson, A C; Wändell, P; Theobald, H
2016-08-01
An increased mortality risk associated with mental disorder has been reported for patients, but there are few studies are based on random samples with interview-based psychiatric diagnoses. Part of the increased mortality for those with mental disorder may be attributable to worse somatic health or hazardous health behaviour - consequences of the disorder - but somatic health information is commonly lacking in psychiatric samples. This study aims to examine long-term mortality risk for psychiatric diagnoses in a general population sample and to assess mediation by somatic ill health and hazardous health behaviour. We used a double-phase stratified random sample of individuals aged 18-65 in Stockholm County 1970-1971 linked to vital records. First phase sample was 32 186 individuals screened with postal questionnaire and second phase was 1896 individuals (920 men and 976 women) that participated in a full-day examination (participation rate 88%). Baseline examination included both a semi-structured interview with a psychiatrist, with mental disorders set according to the 8th version of the International Classification of Disease (ICD-8), and clinical somatic examination, including measures of body composition (BMI), hypertension, fasting blood glucose, pulmonary function and self-reported tobacco smoking. Information on vital status was obtained from the Total Population Register for the years 1970-2011. Associations with mortality were studied with Cox proportional hazard analyses. A total of 883 deaths occurred among the participants during the 41-year follow-up. Increased mortality rates were found for ICD-8 functional psychoses (hazard ratio, HR = 2.22, 95% confidence interval (95% CI): 1.15-4.30); psycho-organic symptoms (HR = 1.94, 95% CI: 1.31-2.87); depressive neuroses (HR = 1.71, 95% CI: 1.23-2.39); alcohol use disorder (HR = 1.91, 95% CI: 1.40-2.61); drug dependence (HR = 3.71, 95% CI: 1.80-7.65) and psychopathy (HR = 2.88, 95% CI: 1.02-8.16). Non-participants (n = 349) had mortality rates similar to participants (HR = 0.98, 95% CI: 0.81-1.18). In subgroup analyses of those with psychoses, depression or alcohol use disorder, adjusting for the potential mediators smoking and pulmonary function, showed only slight changes in the HRs. This study confirms the increased risk of mortality for several psychiatric diagnoses in follow-up studies on American, Finnish and Swedish population-based samples. Only a small part of the increased mortality hazard was attributable to differences in somatic health or hazardous health behaviour measured at baseline.
Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.
Fufaa, Gudeta D; Weil, E Jennifer; Lemley, Kevin V; Knowler, William C; Brosius, Frank C; Yee, Berne; Mauer, Michael; Nelson, Robert G
2016-02-05
Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes. Copyright © 2016 by the American Society of Nephrology.
Right ventricular dysfunction affects survival after surgical left ventricular restoration.
Couperus, Lotte E; Delgado, Victoria; Palmen, Meindert; van Vessem, Marieke E; Braun, Jerry; Fiocco, Marta; Tops, Laurens F; Verwey, Harriëtte F; Klautz, Robert J M; Schalij, Martin J; Beeres, Saskia L M A
2017-04-01
Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Aronson, Doron; Burger, Andrew J
2010-07-01
Worsening renal function (WRF) is an ominous complication in patients with acute heart failure syndrome (AHFS). Few data are available with regard to the clinical implications of transient versus persistent WRF in this setting. We studied 467 patients with AHFS and creatinine measurements at baseline and on days 2, 5, 14, and 30. WRF (>/= 0.5 mg/dL increase in serum creatinine above baseline at any time point) was defined as persistent when serum creatinine remained >/= 0.5 mg/dL above baseline throughout day 30, and transient when creatinine levels subsequently decreased to < 0.5 mg/dL above baseline. WRF occurred in 115 patients, and was transient in 39 patients (33.9%). The 6-month mortality rates were 17.3%, 20.5%, and 46.1% in patients without WRF, transient WRF, and persistent WRF, respectively. In a multivariable Cox model, compared with patients with stable renal function, the adjusted hazard ratio for mortality was 0.8 (95% CI 0.4-1.7; P = .58) in patients with transient WRF and 3.2 (95% CI 2.1-5.0; P < .0001) in patients with persistent WRF. Transient WRF is frequent among patients with AHFS. Whereas persistent WRF portends increased mortality, transient WRF appears to be associated with a better outcome as compared with persistent renal failure. Copyright 2010 Elsevier Inc. All rights reserved.
Regression dilution in the proportional hazards model.
Hughes, M D
1993-12-01
The problem of regression dilution arising from covariate measurement error is investigated for survival data using the proportional hazards model. The naive approach to parameter estimation is considered whereby observed covariate values are used, inappropriately, in the usual analysis instead of the underlying covariate values. A relationship between the estimated parameter in large samples and the true parameter is obtained showing that the bias does not depend on the form of the baseline hazard function when the errors are normally distributed. With high censorship, adjustment of the naive estimate by the factor 1 + lambda, where lambda is the ratio of within-person variability about an underlying mean level to the variability of these levels in the population sampled, removes the bias. As censorship increases, the adjustment required increases and when there is no censorship is markedly higher than 1 + lambda and depends also on the true risk relationship.
Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis
Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana
2017-01-01
Objective Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). Methods AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. Results More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. Conclusion In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. Trial registration number ClinicalTrials.gov identifier: NCT00092677 PMID:28698175
Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis.
Thomassen, Henrik K; Cioffi, Giovanni; Gerdts, Eva; Einarsen, Eigir; Midtbø, Helga Bergljot; Mancusi, Costantino; Cramariuc, Dana
2017-10-01
Sex differences in risk factors of aortic valve calcification (AVC) by echocardiography have not been reported from a large prospective study in aortic stenosis (AS). AVC was assessed using a prognostically validated visual score and grouped into none/mild or moderate/severe AVC in 1725 men and women with asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis study. The severity of AS was assessed by the energy loss index (ELI) taking pressure recovery in the aortic root into account. More men than women had moderate/severe AVC at baseline despite less severe AS by ELI (p<0.01). Moderate/severe AVC at baseline was independently associated with lower aortic compliance and more severe AS in both sexes, and with increased high-sensitive C reactive protein (hs-CRP) only in men (all p<0.01). In Cox regression analyses, moderate/severe AVC at baseline was associated with a 2.5-fold (95% CI 1.64 to 3.80) higher hazard rate of major cardiovascular events in women, and a 2.2-fold higher hazard rate in men (95% CI 1.54 to 3.17) (both p<0.001), after adjustment for age, hypertension, study treatment, aortic compliance, left ventricular (LV) mass and systolic function, AS severity and hs-CRP. Moderate/severe AVC at baseline also predicted a 1.8-fold higher hazard rate of all-cause mortality in men (95% CI 1.04 to 3.06, p<0.05) independent of age, AS severity, LV mass and aortic compliance, but not in women. In conclusion, AVC scored by echocardiography has sex-specific characteristics in AS. Moderate/severe AVC is associated with higher cardiovascular morbidity in both sexes, and with higher all-cause mortality in men. ClinicalTrials.gov identifier: NCT00092677. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Association between Late-Life Social Activity and Motor Decline in Older Adults
Buchman, Aron S.; Boyle, Patricia A.; Wilson, Robert S.; Fleischman, Debra A.; Leurgans, Sue; Bennett, David A.
2009-01-01
Background Loss of motor function is a common consequence of aging, but little is known about factors that predict idiopathic motor decline. Methods We studied 906 persons without dementia, history of stroke or Parkinson's disease participating in the Rush Memory and Aging Project. At baseline, they rated their frequency of participation in common social activities. Outcome was annual change in global motor function, based on nine measures of muscle strength and nine motor performances. Results Mean social activity score at baseline was 2.6 (SD=0.58), with higher scores indicating more frequent participation in social activities. In a generalized estimating equation model, controlling for age, sex and education, motor function declined by about 0.05 unit/year [Estimate, 0.016; 95%CI (-0.057, -0.041); p=0.017]. Each 1-point decrease in social activity was associated with about a 33% more rapid rate of decline in motor function [Estimate, 0.016; 95%CI (0.003, 0.029); p=0.017)]. This amount of annual motor decline was associated with a more than 40% increased risk of death (Hazard Ratio: 1.44; 95%CI: 1.30, 1.60) and 65% increased risk of incident Katz disability (Hazard Ratio: 1.65; 95%CI: 1.48, 1.83). The association of social activity with change in motor function did not vary along demographic lines and was unchanged after controlling for potential confounders including late-life physical and cognitive activity, disability, global cognition, depressive symptoms, body composition and chronic medical conditions [Estimate, 0.025; 95%CI (0.005, 0.045); p=0.010]. Conclusion Less frequent participation in social activities is associated with a more rapid rate of motor decline in old age. PMID:19546415
Amin, Amit P; Spertus, John A; Reid, Kimberly J; Lan, Xiao; Buchanan, Donna M; Decker, Carole; Masoudi, Frederick A
2010-12-01
Although an acute worsening in renal function (WRF) commonly occurs among patients hospitalized for acute myocardial infarction (AMI), its long-term prognostic significance is unknown. We examined predictors of WRF and its association with 4-year mortality. Acute myocardial infarction patients from the multicenter PREMIER study (N=2,098) who survived to hospital discharge were followed for at least 4 years. Worsening in renal function was defined as an increase in creatinine during hospitalization of ≥0.3 mg/dL above the admission value. Correlates of WRF were determined with multivariable logistic regression models and used, along with other important clinical covariates, in Cox proportional hazards models to define the independent association between WRF and mortality. Worsening in renal function was observed in 393 (18.7%) of AMI survivors. Diabetes, left ventricular systolic dysfunction, and a history of chronic kidney disease (documented history of renal failure with baseline creatinine>2.5 mg/dL) were independently associated with WRF. During 4-year follow-up, 386 (18.6%) patients died. Mortality was significantly higher in the WRF group (36.6% vs 14.4% in those without WRF, P<.001). After adjusting for other factors associated with WRF and long-term mortality, including baseline creatinine, WRF was independently associated with a higher risk of death (hazard ratio=1.64, 95% CI 1.23-2.19). Worsening in renal function occurs in approximately 1 of 6 AMI survivors and is independently associated with an adverse long-term prognosis. Further studies on interventions to minimize WRF or to more aggressively treat patients developing WRF should be tested. Copyright © 2010 Mosby, Inc. All rights reserved.
Makizako, Hyuma; Shimada, Hiroyuki; Doi, Takehiko; Tsutsumimoto, Kota; Nakakubo, Sho; Hotta, Ryo; Suzuki, Takao
2017-04-01
Lower extremity functioning is important for maintaining activity in elderly people. Optimal cutoff points for standard measurements of lower extremity functioning would help identify elderly people who are not disabled but have a high risk of developing disability. The purposes of this study were: (1) to determine the optimal cutoff points of the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test for predicting the development of disability and (2) to examine the impact of poor performance on both tests on the prediction of the risk of disability in elderly people dwelling in the community. This was a prospective cohort study. A population of 4,335 elderly people dwelling in the community (mean age = 71.7 years; 51.6% women) participated in baseline assessments. Participants were monitored for 2 years for the development of disability. During the 2-year follow-up period, 161 participants (3.7%) developed disability. The optimal cutoff points of the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test for predicting the development of disability were greater than or equal to 10 seconds and greater than or equal to 9 seconds, respectively. Participants with poor performance on the Five-Times Sit-to-Stand Test (hazard ratio = 1.88; 95% CI = 1.11-3.20), the Timed "Up & Go" Test (hazard ratio = 2.24; 95% CI = 1.42-3.53), or both tests (hazard ratio = 2.78; 95% CI = 1.78-4.33) at the baseline assessment had a significantly higher risk of developing disability than participants who had better lower extremity functioning. All participants had good initial functioning and participated in assessments on their own. Causes of disability were not assessed. Assessments of lower extremity functioning with the Five-Times Sit-to-Stand Test and the Timed "Up & Go" Test, especially poor performance on both tests, were good predictors of future disability in elderly people dwelling in the community. © 2017 American Physical Therapy Association
Aspergillus sensitization or carriage in cystic fibrosis patients.
Fillaux, Judith; Brémont, François; Murris, Marlène; Cassaing, Sophie; Tétu, Laurent; Segonds, Christine; Pipy, Bernard; Magnaval, Jean-François
2014-07-01
Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.
A novel concurrent pictorial choice model of mood-induced relapse in hazardous drinkers.
Hardy, Lorna; Hogarth, Lee
2017-12-01
This study tested whether a novel concurrent pictorial choice procedure, inspired by animal self-administration models, is sensitive to the motivational effect of negative mood induction on alcohol-seeking in hazardous drinkers. Forty-eight hazardous drinkers (scoring ≥7 on the Alcohol Use Disorders Inventory) recruited from the community completed measures of alcohol dependence, depression, and drinking coping motives. Baseline alcohol-seeking was measured by percent choice to enlarge alcohol- versus food-related thumbnail images in two alternative forced-choice trials. Negative and positive mood was then induced in succession by means of self-referential affective statements and music, and percent alcohol choice was measured after each induction in the same way as baseline. Baseline alcohol choice correlated with alcohol dependence severity, r = .42, p = .003, drinking coping motives (in two questionnaires, r = .33, p = .02 and r = .46, p = .001), and depression symptoms, r = .31, p = .03. Alcohol choice was increased by negative mood over baseline (p < .001, ηp2 = .280), and matched baseline following positive mood (p = .54, ηp2 = .008). The negative mood-induced increase in alcohol choice was not related to gender, alcohol dependence, drinking to cope, or depression symptoms (ps ≥ .37). The concurrent pictorial choice measure is a sensitive index of the relative value of alcohol, and provides an accessible experimental model to study negative mood-induced relapse mechanisms in hazardous drinkers. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M
2018-05-15
Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.
10 CFR 850.21 - Hazard assessment.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 10 Energy 4 2011-01-01 2011-01-01 false Hazard assessment. 850.21 Section 850.21 Energy DEPARTMENT... assessment. (a) If the baseline inventory establishes the presence of beryllium, the responsible employer must conduct a beryllium hazard assessment that includes an analysis of existing conditions, exposure...
Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D
2016-09-01
The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.
Association of Physical Activity History With Physical Function and Mortality in Old Age
Koster, Annemarie; Valkeinen, Heli; Patel, Kushang V.; Bandinelli, Stefania; Guralnik, Jack M.; Ferrucci, Luigi
2016-01-01
Background. We examined whether physical activity in early adulthood, late midlife, and old age as well as cumulative physical activity history are associated with changes in physical functioning and mortality in old age. Methods. Data are from participants aged 65 years or older enrolled in the InCHIANTI study who were followed up from 1998–2000 to 2007–2008 (n = 1,149). At baseline, participants recalled their physical activity levels at ages 20–40, 40–60, and in the previous year, and they were categorized as physically inactive, moderately active, and physically active. Physical performance was assessed with the Short Physical Performance Battery and self-reported mobility disability was evaluated at the 3-, 6- and 9-year follow-up. Mortality follow-up was assessed until the end of 2010. Results. Physical inactivity at baseline was associated with greater decline in Short Physical Performance Battery score (mean 9-year change: −2.72, 95% CI: −3.08, −2.35 vs −0.98, 95% −1.57, −0.39) and greater rate of incident mobility disability (hazard ratio 4.66, 95% CI 1.14–19.07) and mortality (hazard ratio 2.18, 95% CI 1.01–4.70) compared to physically active participants at baseline. Being physically active throughout adulthood was associated with smaller decline in physical performance as well as with lower risk of incident mobility disability and premature death compared with those who had been less active during their adult life. Conclusions. Higher cumulative physical activity over the life course was associated with less decline in physical performance and reduced rate of incident mobility disability and mortality in older ages. PMID:26290538
Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas
2017-11-28
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.
Grob, J-J; Amonkar, M M; Martin-Algarra, S; Demidov, L V; Goodman, V; Grotzinger, K; Haney, P; Kämpgen, E; Karaszewska, B; Mauch, C; Miller, W H; Millward, M; Mirakhur, B; Rutkowski, P; Chiarion-Sileni, V; Swann, S; Hauschild, A
2014-07-01
In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18-0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial. The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits. For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks. This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. ClinicalTrials.gov Identifier: NCT01227889. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
The Collision Auto Repair Safety Study (CARSS): a health and safety intervention.
Parker, David L; Bejan, Anca; Brosseau, Lisa M; Skan, Maryellen; Xi, Min
2015-01-01
Collision repair employs approximately 205,500 people in 33,400 shops. Workers are exposed to a diverse array of chemical, physical, and ergonomic hazards. CARSS was based on a random and purposeful sample. Baseline and one baseline and one-year evaluations consisted of 92 questions addressing issues, such as Right-to-Know, fire protection, painting-related hazards, ergonomics, electrical safety, and personal protective equipment. Owners received a report and selected at least 30% of items found deficient for remediation. In-person and web-based services were provided. Forty-nine shops were evaluated at baseline and 45 at follow-up. At baseline, 54% of items were present. This improved to 71% at follow-up (P < 0.0001). Respiratory protection improved 37% (P < 0.0001) and Right-to-Know training increased 30% (P < 0.0001). Owners completed 61% of items they selected for remediation. Small businesses' interventions should address the lack of personnel and administrative infrastructure. Tailored information regarding hazards and easy-to-use training and administrative programs overcome many barriers to improvement. © 2014 Wiley Periodicals, Inc.
Liang, Xinyun; Famure, Olusegun; Li, Yanhong; Kim, S Joseph
2018-06-01
Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models. A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia. These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.
Remontet, L; Bossard, N; Belot, A; Estève, J
2007-05-10
Relative survival provides a measure of the proportion of patients dying from the disease under study without requiring the knowledge of the cause of death. We propose an overall strategy based on regression models to estimate the relative survival and model the effects of potential prognostic factors. The baseline hazard was modelled until 10 years follow-up using parametric continuous functions. Six models including cubic regression splines were considered and the Akaike Information Criterion was used to select the final model. This approach yielded smooth and reliable estimates of mortality hazard and allowed us to deal with sparse data taking into account all the available information. Splines were also used to model simultaneously non-linear effects of continuous covariates and time-dependent hazard ratios. This led to a graphical representation of the hazard ratio that can be useful for clinical interpretation. Estimates of these models were obtained by likelihood maximization. We showed that these estimates could be also obtained using standard algorithms for Poisson regression. Copyright 2006 John Wiley & Sons, Ltd.
2002-10-01
To examine the relationships between baseline risk factors and sustained decrease of visual field (SDVF) and sustained decrease of visual acuity (SDVA). Cohort study of participants in the Advanced Glaucoma Intervention Study (AGIS). This multicenter study enrolled patients between 1988 and 1992 and followed them until 2001; 789 eyes of 591 patients with advanced glaucoma were randomly assigned to one of two surgical sequences, argon laser trabeculoplasty (ALT)-trabeculectomy-trabeculectomy (ATT) or trabeculectomy-ALT-trabeculectomy (TAT). This report is based on data from 747 eyes. Eyes were offered the next intervention in the sequence upon failure of the previous intervention. Failure was based on recurrent intraocular pressure elevation, visual field defect, and disk rim criteria. Study visits occurred every 6 months; potential follow-up ranged from 8 to 13 years. For each intervention sequence, Cox multiple regression analyses were used to examine the baseline characteristics for association with two vision outcomes: SDVF and SDVA. The magnitude of the association is measured by the hazard ratio (HR), where HR for binary variables is the relative change in the hazard (or risk) of the outcome in eyes with the factor divided by the hazard in eyes without the factor, and HR for continuous variables is the relative change in the hazard (or risk) of the outcome in eyes with a unit increase in the factor. Characteristics associated with increased SDVF risk in the ATT sequence are: less baseline visual field defect (hazard ratio [HR] = 0.86, P <.001, 95% CI = 0.82-0.90), male gender (HR = 2.23, P <.001, 1.54-3.23), and worse baseline visual acuity (HR = 0.96, P =.001, 0.94-0.98); in the TAT sequence: less baseline visual field defect (HR = 0.93, P =.001, 0.89-0.97) and diabetes (HR = 1.87, P =.007, 1.18-2.97). Characteristics associated with increased SDVA risk in both treatment sequences are better baseline acuity (ATT: HR = 1.05, P <.001, 1.02-1.09; TAT: HR = 1.06, P <.001, 1.03-1.08), older age (ATT: HR = 1.05, P =.001, 1.02-1.08; TAT: HR = 1.04, P =.002, 1.01-1.06), and less formal education (ATT: HR = 1.92, P =.001, 1.29-2.88; TAT: HR = 1.77, P =.002, 1.22-2.54). For SDVF, risk factors were better baseline visual field in both treatment sequences, male gender, and worse baseline visual acuity in the ATT sequence, and diabetes in the TAT sequence. For SDVA, risk factors in both treatment sequences were better baseline visual acuity, older age, and less formal education.
Prediction of functional loss in glaucoma from progressive optic disc damage.
Medeiros, Felipe A; Alencar, Luciana M; Zangwill, Linda M; Bowd, Christopher; Sample, Pamela A; Weinreb, Robert N
2009-10-01
To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.
Donham, K J; Reynolds, S J; Whitten, P; Merchant, J A; Burmeister, L; Popendorf, W J
1995-03-01
Human respiratory health hazards for people working in livestock confinement buildings have been recognized since 1974. However, before comprehensive control programs can be implemented, more knowledge is needed of specific hazardous substances present in the air of these buildings, and at what concentrations they are harmful. Therefore, a medical epidemiological and exposure-response study was conducted on 207 swine producers using intensive housing systems (108 farms). Dose-response relationships between pulmonary function and exposures are reported here. Positive correlations were seen between change in pulmonary function over a work period and exposure to total dust, respirable dust, ammonia, respirable endotoxin, and the interactions of age-of-producer and dust exposure and years-of-working-in-the-facility and dust exposure. Relationships between baseline pulmonary function and exposures were not strong and therefore, not pursued in this study. The correlations between exposure and response were stronger after 6 years of exposure. Multiple regression models were used to identify total dust and ammonia as the two primary environmental predictors of pulmonary function decrements over a work period. The regression models were then used to determine exposure concentrations related to pulmonary function decrements suggestive of a health hazard. Total dust concentrations > or = 2.8 mg/m3 were predictive of a work period decrement of > or = 10% in FEV1. Ammonia concentrations of > or = 7.5 ppm were predictive of a > or = 3% work period decrement in FEV1. These predictive concentrations were similar to a previous dose-response study, which suggested 2.5 mg/m3 of total dust and 7 ppm of NH3 were associated with significant work period decrements. Therefore, dust > or = 2.8 mg/m3 and ammonia > or = 7.5 ppm should be considered reasonable evidence for guidelines regarding hazardous exposure concentrations in this work environment.
NASA Technical Reports Server (NTRS)
Rutishauser, David K.; Epp, Chirold; Robertson, Ed
2012-01-01
The Autonomous Landing Hazard Avoidance Technology (ALHAT) Project is chartered to develop and mature to a Technology Readiness Level (TRL) of six an autonomous system combining guidance, navigation and control with terrain sensing and recognition functions for crewed, cargo, and robotic planetary landing vehicles. The ALHAT System must be capable of identifying and avoiding surface hazards to enable a safe and accurate landing to within tens of meters of designated and certified landing sites anywhere on a planetary surface under any lighting conditions. Since its inception in 2006, the ALHAT Project has executed four field test campaigns to characterize and mature sensors and algorithms that support real-time hazard detection and global/local precision navigation for planetary landings. The driving objective for Government Fiscal Year 2012 (GFY2012) is to successfully demonstrate autonomous, real-time, closed loop operation of the ALHAT system in a realistic free flight scenario on Earth using the Morpheus lander developed at the Johnson Space Center (JSC). This goal represents an aggressive target consistent with a lean engineering culture of rapid prototyping and development. This culture is characterized by prioritizing early implementation to gain practical lessons learned and then building on this knowledge with subsequent prototyping design cycles of increasing complexity culminating in the implementation of the baseline design. This paper provides an overview of the ALHAT/Morpheus flight demonstration activities in GFY2012, including accomplishments, current status, results, and lessons learned. The ALHAT/Morpheus effort is also described in the context of a technology path in support of future crewed and robotic planetary exploration missions based upon the core sensing functions of the ALHAT system: Terrain Relative Navigation (TRN), Hazard Detection and Avoidance (HDA), and Hazard Relative Navigation (HRN).
Population-based absolute risk estimation with survey data
Kovalchik, Stephanie A.; Pfeiffer, Ruth M.
2013-01-01
Absolute risk is the probability that a cause-specific event occurs in a given time interval in the presence of competing events. We present methods to estimate population-based absolute risk from a complex survey cohort that can accommodate multiple exposure-specific competing risks. The hazard function for each event type consists of an individualized relative risk multiplied by a baseline hazard function, which is modeled nonparametrically or parametrically with a piecewise exponential model. An influence method is used to derive a Taylor-linearized variance estimate for the absolute risk estimates. We introduce novel measures of the cause-specific influences that can guide modeling choices for the competing event components of the model. To illustrate our methodology, we build and validate cause-specific absolute risk models for cardiovascular and cancer deaths using data from the National Health and Nutrition Examination Survey. Our applications demonstrate the usefulness of survey-based risk prediction models for predicting health outcomes and quantifying the potential impact of disease prevention programs at the population level. PMID:23686614
Schueler, Robert; Öztürk, Can; Sinning, Jan-Malte; Werner, Nikos; Welz, Armin; Hammerstingl, Christoph; Nickenig, Georg
2017-05-01
Tricuspid regurgitation (TR) in patients with mitral valve disease is associated with poor outcome and mortality. Only limited data on the impact of TR on functional outcome and survival in patients undergoing MitraClip procedures are available. 261 patients (mean age 76.6 ± 10, EuroScore 15.9 ± 15.1%) with symptomatic mitral regurgitation (MR) (75.2% functional MR) undergoing MitraClip procedure were included and followed for 721 ± 19.4 days. At baseline 54.7% presented with TR grade 0/I, 29.5% with grade II, 13.4% with grade III and 2.3% with grade IV. When dividing groups according to baseline TR grades, follow-up (FU)-NYHA class was significantly improved only in patients with TR ≤ II (p = 0.05). FU-6-min walking distance increased significantly in the overall cohort (p = 0.05), in patients with TR ≤ II (p = 0.007), but not in patients with TR > II (p = 0.4). Moreover, FU-NT-pro-BNP levels were higher in patients with TR > II (p = 0.05), compared to patients with TR ≤ II. There was a higher mortality according to baseline TR > II and multivariate Cox regression revealed TR > II as the strongest independent predictor for mortality (hazard ratio 2.04). Concomitant TR at baseline negatively influences functional outcome and mortality in patients undergoing MitraClip procedures. Our results underline the need for dedicated interventional strategies for the treatment of TR in patients with symptomatic MR.
Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X
2018-06-22
The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.
Loftfield, Erikka; Freedman, Neal D; Graubard, Barry I; Guertin, Kristin A; Black, Amanda; Huang, Wen-Yi; Shebl, Fatma M; Mayne, Susan T; Sinha, Rashmi
2015-12-15
Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998-2001) or history of cardiovascular disease at study enrollment (1993-2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2-3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4-5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Loftfield, Erikka; Freedman, Neal D.; Graubard, Barry I.; Guertin, Kristin A.; Black, Amanda; Huang, Wen-Yi; Shebl, Fatma M.; Mayne, Susan T.; Sinha, Rashmi
2015-01-01
Abstract Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998–2001) or history of cardiovascular disease at study enrollment (1993–2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (<1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2–3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4–5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression. PMID:26614599
Estimation of variance in Cox's regression model with shared gamma frailties.
Andersen, P K; Klein, J P; Knudsen, K M; Tabanera y Palacios, R
1997-12-01
The Cox regression model with a shared frailty factor allows for unobserved heterogeneity or for statistical dependence between the observed survival times. Estimation in this model when the frailties are assumed to follow a gamma distribution is reviewed, and we address the problem of obtaining variance estimates for regression coefficients, frailty parameter, and cumulative baseline hazards using the observed nonparametric information matrix. A number of examples are given comparing this approach with fully parametric inference in models with piecewise constant baseline hazards.
Garcia-Hernandez, Alberto
2014-03-01
Although the quality-adjusted life-years (QALY) model is standard in health technology assessment, quantitative methods are less frequent but increasingly used for benefit-risk assessment (BRA) at earlier stages of drug development. A frequent challenge when implementing metrics for BRA is to weigh the importance of effects on a chronic condition against the risk of severe events during the trial. The lifetime component of the QALY model has a counterpart in the BRA context, namely, the risk of dying during the study. A new concept is presented, the hazard of death function that a subject is willing to accept instead of the baseline hazard to improve his or her chronic health status, which we have called the quality-of-life-adjusted hazard of death. It has been proven that if assumptions of the linear QALY model hold, the excess mortality rate tolerated by a subject for a chronic health improvement is inversely proportional to the mean residual life. This result leads to a new representation of the linear QALY model in terms of hazard rate functions and allows utilities obtained by using standard methods involving trade-offs of life duration to be translated into thresholds of tolerated mortality risk during a short period of time, thereby avoiding direct trade-offs using small probabilities of events during the study, which is known to lead to bias and variability. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Lee, Jong-Young; Ryu, Seungho; Sung, Ki-Chul
2018-01-01
Background The association between baseline and temporal changes in physical activity and incident hypertension or diabetes mellitus in initially non-hypertensive or non-diabetic subjects is rarely known. Methods Among individuals who underwent consecutive comprehensive health screenings, their physical activity level was measured using a self-reported international physical activity questionnaire. First, subjects were classified into four categories: no regular physical activity with a sedentary lifestyle; minimal physical activity (<75 min/week); insufficient physical activity (≥75 min but <150 min/week); and sufficient physical activity (≥150 min/week). Second, subjects were sub-grouped, based on temporal changes in physical activity level between baseline and consecutive follow-up: increase, no change, and decrease. Results Finally, among 174,314 subjects (mean age 36.7 ± 6.9 years), 5544 (3.18%) and 21,276 (12.2%) developed incident diabetes mellitus and arterial hypertension, respectively. After a multivariate adjustment, sufficient baseline physical activity was associated with significantly lower risk for incident hypertension (hazard ratio 0.89; 95% confidence interval (CI) 0.81 to 0.97), but the difference was not significant, and showed a lower trend in diabetes mellitus incidence (hazard ratio 0.87; 95% CI 0.69 to 1.04) in reference to no regular physical activity group. Regardless of the baseline physical activity level, subjects with a temporal increase in physical activity showed significantly decreased risk for incident hypertension (hazard ratio 0.93; 95% CI 0.87 to 0.99) and diabetes mellitus (hazard ratio 0.83; 95% CI 0.74 to 0.92) compared with those with a temporal decrease in their physical activity level. Conclusion Both sufficient baseline physical activity level and its temporal increase were associated with a lower risk of incident hypertension and diabetes mellitus in a large, relatively healthy, cohort.
Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A.
2012-01-01
Background Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Study Design Observational cohort study. Setting & Participants 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Predictor Baseline estimated glomerular filtration rate (eGFR). Outcomes Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m2 for >3 months) in Cox proportional hazards and competing-risk regression models. Results Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m2. Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m2 remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m2 was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m2 and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m2. Limitations The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Conclusions Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. PMID:22521282
Felker, G Michael; Fiuzat, Mona; Thompson, Vivian; Shaw, Linda K; Neely, Megan L; Adams, Kirkwood F; Whellan, David J; Donahue, Mark P; Ahmad, Tariq; Kitzman, Dalane W; Piña, Ileana L; Zannad, Faiez; Kraus, William E; O'Connor, Christopher M
2013-11-01
ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in heart failure (HF). We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study-a multicenter, randomized study of exercise training in HF. HF-ACTION randomized 2331 patients with left ventricular ejection fraction <0.35 and New York Heart Association class II to IV HF to either exercise training or usual care. ST2 was analyzed in a subset of 910 patients with evaluable plasma samples. Correlations and Cox models were used to assess the relationship among ST2, functional capacity, and long-term outcomes. The median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2 was modestly associated with measures of functional capacity. In univariable analysis, ST2 was significantly associated with death or hospitalization (hazard ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio, 2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all hazard ratios for log2 ng/mL). In multivariable models, ST2 remained independently associated with outcomes after adjustment for clinical variables and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add significantly to reclassification of risk as assessed by changes in the C statistic, net reclassification improvement, and integrated discrimination improvement. ST2 was modestly associated with functional capacity and was significantly associated with outcomes in a well-treated cohort of ambulatory patients with HF although it did not significantly affect reclassification of risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.
Hernández, Domingo; Sánchez-Fructuoso, Ana; González-Posada, José Manuel; Arias, Manuel; Campistol, Josep María; Rufino, Margarita; Morales, José María; Moreso, Francesc; Pérez, Germán; Torres, Armando; Serón, Daniel
2009-09-27
All-cause mortality is high after kidney transplantation (KT), but no prognostic index has focused on predicting mortality in KT using baseline and emergent comorbidity after KT. A total of 4928 KT recipients were used to derive a risk score predicting mortality. Patients were randomly assigned to two groups: a modeling population (n=2452), used to create a new index, and a testing population (n=2476), used to test this index. Multivariate Cox regression model coefficients of baseline (age, weight, time on dialysis, diabetes, hepatitis C, and delayed graft function) and emergent comorbidity within the first posttransplant year (diabetes, proteinuria, renal function, and immunosuppressants) were used to weigh each variable in the calculation of the score and allocated into risk quartiles. The probability of death at 3 years, estimated by baseline cumulative hazard function from the Cox model [P (death)=1-0.993592764 (exp(score/100)], increased from 0.9% in the lowest-risk quartile (score=40) to 4.7% in the highest risk-quartile (score=200). The observed incidence of death increased with increasing risk quartiles in testing population (log-rank analysis, P<0.0001). The overall C-index was 0.75 (95% confidence interval: 0.72-0.78) and 0.74 (95% confidence interval: 0.70-0.77) in both populations, respectively. This new index is an accurate tool to identify high-risk patients for mortality after KT.
Recovery Expectations and Long-term Prognosis of Patients With Coronary Heart Disease
Barefoot, John C.; Brummett, Beverly H.; Williams, Redford B.; Siegler, Ilene C.; Helms, Michael J.; Boyle, Stephen H.; Clapp-Channing, Nancy E.; Mark, Daniel B.
2013-01-01
Background Expectations of patients regarding their prospects for recovery have been shown to predict subsequent physical and social functioning. Evidence regarding the impact of expectations on clinical outcomes is limited. Methods At the inpatient service of a tertiary care hospital, we evaluated beliefs of patients undergoing coronary angiography about their prognosis as predictors of long-term survival and 1-year functional status. Baseline assessments, including a measure of expectations for recovery, were obtained during hospitalization with mortality follow-up for approximately 15 years. Patients with significant obstructive coronary artery disease were interviewed while in the hospital and enrolled in follow-up. Functional status was assessed at baseline and 1 year later with questionnaires reflecting physical capabilities. Analyses controlled for age, sex, disease severity, comorbidities, treatments, demographics, depressive symptoms, social support, and functional status. There were 1637 total deaths, 885 from cardiovascular causes, in the 2818 patients in these analyses. The outcomes were total mortality, cardiovascular mortality, and 1-year functional status. Results Expectations were positively associated with survival after controlling for background and clinical disease indicators. For a difference equivalent to an inter-quartile range of expectations, the hazard ratio (HR) for total mortality was 0.76 (95% confidence interval [CI], 0.71–0.82) and 0.76 (95% CI, 0.69–0.83) for cardiovascular mortality. The HRs were 0.83 (95% CI, 0.76–0.91) and 0.79 (95% CI, 0.70–0.89) with further adjustments for demographic and psychosocial covariates. Similar associations (P<.001) were observed for functional status. Conclusion Recovery expectations at baseline were positively associated with long-term survival and functioning in patients with coronary artery disease. PMID:21357800
Recovery expectations and long-term prognosis of patients with coronary heart disease.
Barefoot, John C; Brummett, Beverly H; Williams, Redford B; Siegler, Ilene C; Helms, Michael J; Boyle, Stephen H; Clapp-Channing, Nancy E; Mark, Daniel B
2011-05-23
Expectations of patients regarding their prospects for recovery have been shown to predict subsequent physical and social functioning. Evidence regarding the impact of expectations on clinical outcomes is limited. At the inpatient service of a tertiary care hospital, we evaluated beliefs of patients undergoing coronary angiography about their prognosis as predictors of long-term survival and 1-year functional status. Baseline assessments, including a measure of expectations for recovery, were obtained during hospitalization with mortality follow-up for approximately 15 years. Patients with significant obstructive coronary artery disease were interviewed while in the hospital and enrolled in follow-up. Functional status was assessed at baseline and 1 year later with questionnaires reflecting physical capabilities. Analyses controlled for age, sex, disease severity, comorbidities, treatments, demographics, depressive symptoms, social support, and functional status. There were 1637 total deaths, 885 from cardiovascular causes, in the 2818 patients in these analyses. The outcomes were total mortality, cardiovascular mortality, and 1-year functional status. Expectations were positively associated with survival after controlling for background and clinical disease indicators. For a difference equivalent to an interquartile range of expectations, the hazard ratio (HR) for total mortality was 0.76 (95% confidence interval [CI], 0.71-0.82) and 0.76 (95% CI, 0.69-0.83) for cardiovascular mortality. The HRs were 0.83 (95% CI, 0.76-0.91) and 0.79 (95% CI, 0.70-0.89) with further adjustments for demographic and psychosocial covariates. Similar associations (P < .001) were observed for functional status. Recovery expectations at baseline were positively associated with long-term survival and functioning in patients with coronary artery disease.
Shams, Tanzila; Auchus, Alexander P; Oparil, Suzanne; Wright, Clinton B; Wright, Jackson; Furlan, Anthony J; Sila, Cathy A; Davis, Barry R; Pressel, Sara; Yamal, Jose-Miguel; Einhorn, Paula T; Lerner, Alan J
2017-11-01
The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups ( P ≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.
Suzuki, Takeki; Agarwal, Sunil K; Deo, Rajat; Sotoodehnia, Nona; Grams, Morgan E; Selvin, Elizabeth; Calkins, Hugh; Rosamond, Wayne; Tomaselli, Gordon; Coresh, Josef; Matsushita, Kunihiro
2016-10-01
Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD. We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β2-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders. Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90mL/(min 1.73m(2)) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers). Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context. Copyright © 2016 Elsevier Inc. All rights reserved.
Beer, Tomasz M; Miller, Kurt; Tombal, Bertrand; Cella, David; Phung, De; Holmstrom, Stefan; Ivanescu, Cristina; Skaltsa, Konstantina; Naidoo, Shevani
2017-12-01
Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival. Copyright © 2017 Elsevier Ltd. All rights reserved.
A Tutorial on Multilevel Survival Analysis: Methods, Models and Applications
Austin, Peter C.
2017-01-01
Summary Data that have a multilevel structure occur frequently across a range of disciplines, including epidemiology, health services research, public health, education and sociology. We describe three families of regression models for the analysis of multilevel survival data. First, Cox proportional hazards models with mixed effects incorporate cluster-specific random effects that modify the baseline hazard function. Second, piecewise exponential survival models partition the duration of follow-up into mutually exclusive intervals and fit a model that assumes that the hazard function is constant within each interval. This is equivalent to a Poisson regression model that incorporates the duration of exposure within each interval. By incorporating cluster-specific random effects, generalised linear mixed models can be used to analyse these data. Third, after partitioning the duration of follow-up into mutually exclusive intervals, one can use discrete time survival models that use a complementary log–log generalised linear model to model the occurrence of the outcome of interest within each interval. Random effects can be incorporated to account for within-cluster homogeneity in outcomes. We illustrate the application of these methods using data consisting of patients hospitalised with a heart attack. We illustrate the application of these methods using three statistical programming languages (R, SAS and Stata). PMID:29307954
A Tutorial on Multilevel Survival Analysis: Methods, Models and Applications.
Austin, Peter C
2017-08-01
Data that have a multilevel structure occur frequently across a range of disciplines, including epidemiology, health services research, public health, education and sociology. We describe three families of regression models for the analysis of multilevel survival data. First, Cox proportional hazards models with mixed effects incorporate cluster-specific random effects that modify the baseline hazard function. Second, piecewise exponential survival models partition the duration of follow-up into mutually exclusive intervals and fit a model that assumes that the hazard function is constant within each interval. This is equivalent to a Poisson regression model that incorporates the duration of exposure within each interval. By incorporating cluster-specific random effects, generalised linear mixed models can be used to analyse these data. Third, after partitioning the duration of follow-up into mutually exclusive intervals, one can use discrete time survival models that use a complementary log-log generalised linear model to model the occurrence of the outcome of interest within each interval. Random effects can be incorporated to account for within-cluster homogeneity in outcomes. We illustrate the application of these methods using data consisting of patients hospitalised with a heart attack. We illustrate the application of these methods using three statistical programming languages (R, SAS and Stata).
Lanfear, David E.; Peterson, Edward L.; Campbell, Janis; Phatak, Hemant; Wu, David; Wells, Karen; Spertus, John A.; Williams, L. Keoki
2010-01-01
Worsened renal function (WRF) during heart failure (HF) hospitalization is associated with in-hospital mortality, but there are limited data regarding its relationship to long-term outcomes after discharge. The influence of WRF resolution is also unknown. This retrospective study analyzed patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between 1/2000 and 6/2008. Renal function was estimated from creatinine levels during hospitalization. The first available value was considered baseline. WRF was defined a creatinine increase of ≥0.3mg/dl on any subsequent hospital day compared to baseline. Persistent WRF was defined as having WRF at discharge. Proportional hazards regression, adjusting for baseline renal function and potential confounding factors, was used to assess time to re-hospitalization or death. Among 2465 patients who survived to discharge, 887 (36%) developed WRF. Median follow up was 2.1 years. In adjusted models, WRF was associated with higher rates of post-discharge death or re-hospitalization (HR 1.12, 95%CI 1.02 – 1.22). Among those with WRF, 528 (60%) had persistent WRF while 359 (40%) recovered. Persistent WRF was significantly associated with higher post-discharge event rates (HR 1.14, 95%CI 1.02 – 1.27), whereas transient WRF showed only a non-significant trend towards risk (HR 1.09 95%CI 0.96-1.24). In conclusion, among patients surviving hospitalization for HF, WRF was associated with increased long-term mortality and re-hospitalization, particularly if renal function did not recover by the time of discharge. PMID:21146690
Age at menopause and incident heart failure: the Multi-Ethnic Study of Atherosclerosis.
Ebong, Imo A; Watson, Karol E; Goff, David C; Bluemke, David A; Srikanthan, Preethi; Horwich, Tamara; Bertoni, Alain G
2014-06-01
This study aims to evaluate the associations of early menopause (menopause occurring before age 45 years) and age at menopause with incident heart failure (HF) in postmenopausal women. We also explored the associations of early menopause and age at menopause with left ventricular (LV) measures of structure and function in postmenopausal women. We included 2,947 postmenopausal women, aged 45 to 84 years without known cardiovascular disease (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Cox proportional hazards models were used to examine the associations of early menopause and age at menopause with incident HF. In 2,123 postmenopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored the associations of early menopause and age at menopause with LV measures using multivariable linear regression. Across a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (Pinteraction > 0.05). In adjusted analysis, early menopause was associated with an increased risk of incident HF (hazard ratio, 1.66; 95% CI, 1.01-2.73), whereas every 1-year increase in age at menopause was associated with a decreased risk of incident HF (hazard ratio, 0.96; 95% CI, 0.94-0.99). We observed significant interactions between early menopause and ethnicity for LV mass-to-volume ratio (LVMVR; Pinteraction = 0.02). In Chinese-American women, early menopause was associated with a higher LVMVR (+0.11; P = 0.0002), whereas every 1-year increase in age at menopause was associated with a lower LVMVR (-0.004; P = 0.04) at baseline. Older age at menopause is independently associated with a decreased risk of incident HF. Concentric LV remodeling, indicated by a higher LVMVR, is present in Chinese-American women who experienced early menopause at baseline.
Guidance for conducting hazardous materials flow surveys
DOT National Transportation Integrated Search
1995-01-01
This report provides guidance on how to conduct a commodity flow study for hazardous materials moving by highway. It discusses the need for this type of study and details how to review baseline information and design the study. It includes examples a...
Buchman, Aron S.; Boyle, Patricia A.; Leurgans, Sue E.; Barnes, Lisa L.; Bennett, David A.
2010-01-01
Objective To examine the association of cognitive function with the risk of incident mobility impairments and the rate of declining mobility in older adults. Design Prospective, observational cohort study. Setting Retirement communities across metropolitan Chicago. Participants 1154 ambulatory elders from two longitudinal studies without baseline clinical dementia or history of stroke or Parkinson’s disease. Measurements All participants underwent baseline cognitive testing and annual mobility exams. Mobility impairments were based on annual timed walking performance. A composite mobility measure which summarized gait and balance measures was used to examine the annual rate of mobility change. Results During follow-up of 4.5 years, 423 of 836 (50.6%) participants developed impaired mobility. In a proportional hazards model controlled for age, sex, education and race, each 1-unit higher level of baseline global cognition was associated with a reduction to about half in the risk of mobility impairments (HR=0.51, 95% CI 0.40, 0.66) and was similar to a participant being about 13 years younger at baseline. These results did not vary by sex or race and were unchanged in analyses controlling for BMI, physical activity, vascular diseases and risk factors. The level of cognition in 5 different cognitive abilities was also related to incident mobility impairment. Cognition showed similar associations with incident loss of the ability to ambulate. Linear mixed-effects models showed that global cognition at baseline was associated with the rate of declining mobility. Conclusions Among ambulatory elders, cognition is associated with incident mobility impairment and mobility decline. PMID:21606900
Ambrosy, Andrew P; Bhatt, Ankeet S; Stebbins, Amanda L; Wruck, Lisa M; Fudim, Marat; Greene, Stephen J; Kraus, William E; O'Connor, Christopher M; Piña, Ileana L; Whellan, David J; Mentz, Robert J
2018-05-01
Despite more than 200 years of clinical experience and a pivotal trial, recently published research has called into question the safety and efficacy of digoxin therapy in heart failure (HF). HF-ACTION (ClinicalTrials.gov Number: NCT00047437) enrolled 2331 outpatients with HF and an EF ≤35% between April 2003 and February 2007 and randomized them to aerobic exercise training versus usual care. Patients were grouped according to prevalent digoxin status at baseline. The association between digoxin therapy and outcomes was assessed using Cox proportional hazard and inverse-probability weighted (IPW) regression models adjusted for demographics, medical history, medications, laboratory values, quality of life, and exercise parameters. The prevalence of digoxin therapy decreased from 52% during the first 6 months of enrollment to 35% at the end of the HF-ACTION trial (P <0.0001). Study participants were 59± 13 years of age, 72% were male, and approximately half had an ischemic etiology of HF. Patients receiving digoxin at baseline tended to be younger and were more likely to report New York Heart Association functional class III/IV symptoms (rather than class II) compared to those not receiving digoxin. Patients taking digoxin had worse baseline exercise capacity as measured by peak VO 2 and 6-min walk test and greater impairments in health status as reflected by the Kansas City Cardiomyopathy Questionnaire. The association between digoxin and the risk of death or hospitalization differed depending on whether Cox proportional hazard (Hazard Ratio 1.03, 95% Confidence Interval 0.92-1.16; P = .62) or IPW regression models (HR 1.08, 95% CI 1.00-1.17; P = .057) were used to adjust for potential confounders. Although digoxin use was associated with high-risk clinical features, the association between digoxin therapy and outcomes was dependent on the statistical methods used for multivariable adjustment. Clinical equipoise exists and additional prospective research is required to clarify the role of digoxin in contemporary clinical practice including its effects on functional capacity, quality of life, and long-term outcomes. Copyright © 2018. Published by Elsevier Inc.
Memory Binding Test Predicts Incident Amnestic Mild Cognitive Impairment.
Mowrey, Wenzhu B; Lipton, Richard B; Katz, Mindy J; Ramratan, Wendy S; Loewenstein, David A; Zimmerman, Molly E; Buschke, Herman
2016-07-14
The Memory Binding Test (MBT), previously known as Memory Capacity Test, has demonstrated discriminative validity for distinguishing persons with amnestic mild cognitive impairment (aMCI) and dementia from cognitively normal elderly. We aimed to assess the predictive validity of the MBT for incident aMCI. In a longitudinal, community-based study of adults aged 70+, we administered the MBT to 246 cognitively normal elderly adults at baseline and followed them annually. Based on previous work, a subtle reduction in memory binding at baseline was defined by a Total Items in the Paired (TIP) condition score of ≤22 on the MBT. Cox proportional hazards models were used to assess the predictive validity of the MBT for incident aMCI accounting for the effects of covariates. The hazard ratio of incident aMCI was also assessed for different prediction time windows ranging from 4 to 7 years of follow-up, separately. Among 246 controls who were cognitively normal at baseline, 48 developed incident aMCI during follow-up. A baseline MBT reduction was associated with an increased risk for developing incident aMCI (hazard ratio (HR) = 2.44, 95% confidence interval: 1.30-4.56, p = 0.005). When varying the prediction window from 4-7 years, the MBT reduction remained significant for predicting incident aMCI (HR range: 2.33-3.12, p: 0.0007-0.04). Persons with poor performance on the MBT are at significantly greater risk for developing incident aMCI. High hazard ratios up to seven years of follow-up suggest that the MBT is sensitive to early disease.
Säfsten, Eleonor; Forsell, Yvonne; Ramstedt, Mats; Galanti, Maria R
2018-06-01
Adopting healthy behaviours may facilitate the transition from hazardous to non-hazardous use of alcohol, yet, longitudinal studies of health behaviours in relation to the cessation of hazardous alcohol use are rare. We addressed this question using data from a large population-based cohort of adults in Sweden (Stockholm Public Health Cohort). Participants from two sub-cohorts (inception in 2002 and 2010), with follow-up until the year 2014 were included. Health behaviours (tobacco use, diet and physical activity) and alcohol use were self-reported in questionnaire-based surveys. Hazardous alcohol use was defined as either usual weekly consumption (2002 sub-cohort) or heavy occasional alcohol consumption (2010 sub-cohort). Baseline hazardous drinkers with complete data constituted the analytical sample (n = 8946). Logistic regression was used to calculate the Odds Ratios and their 95% confidence intervals of quitting hazardous alcohol use, with tobacco use, diet and physical activity as predictors of change. In the 2002 sub-cohort, 28% reported non-hazardous use sustained through two consecutive follow-up points. In the 2010 sub-cohort, 36% of the participants reported non-hazardous use of alcohol at follow-up. Favourable health behaviours at baseline (e.g. no tobacco use, sufficient fruit intake and physical activity) were associated with a 19% to 75% higher of odds quitting hazardous alcohol use. Further, favourable changes in diet and tobacco cessation were associated with non-hazardous alcohol use at follow-up. As many as one-third of hazardous alcohol users may quit this drinking pattern in a medium-long term. Holding or achieving a healthy lifestyle may facilitate this transition.
Fox, Kenneth R.; Ku, Po-Wen; Hillsdon, Melvyn; Davis, Mark G.; Simmonds, Bethany A. J.; Thompson, Janice L.; Stathi, Afroditi; Gray, Selena F.; Sharp, Deborah J.; Coulson, Joanne C.
2015-01-01
Background: objective measures of physical activity and function with a diverse cohort of UK adults in their 70s and 80s were used to investigate relative risk of all-cause mortality and diagnoses of new diseases over a 4-year period. Participants: two hundred and forty older adults were randomly recruited from 12 general practices in urban and suburban areas of a city in the United Kingdom. Follow-up included 213 of the baseline sample. Methods: socio-demographic variables, height and weight, and self-reported diagnosed diseases were recorded at baseline. Seven-day accelerometry was used to assess total physical activity, moderate-to-vigorous activity and sedentary time. A log recorded trips from home. Lower limb function was assessed using the Short Physical Performance Battery. Medical records were accessed on average 50 months post baseline, when new diseases and deaths were recorded. Analyses: ANOVAs were used to assess socio-demographic, physical activity and lower limb function group differences in diseases at baseline and new diseases during follow-up. Regression models were constructed to assess the prospective associations between physical activity and function with mortality and new disease. Results: for every 1,000 steps walked per day, the risk of mortality was 36% lower (hazard ratios 0.64, 95% confidence interval (CI) 0.44–0.91, P = 0.013). Low levels of moderate-to-vigorous physical activity (incident rate ratio (IRR) 1.67, 95% CI 1.04–2.68, P = 0.030) and low frequency of trips from home (IRR 1.41, 95% CI 0.98–2.05, P = 0.045) were associated with diagnoses of more new diseases. Conclusion: physical activity should be supported for adults in their 70s and 80s, as it is associated with reduced risk of mortality and new disease development. PMID:25377744
Fox, Kenneth R; Ku, Po-Wen; Hillsdon, Melvyn; Davis, Mark G; Simmonds, Bethany A J; Thompson, Janice L; Stathi, Afroditi; Gray, Selena F; Sharp, Deborah J; Coulson, Joanne C
2015-03-01
Objective measures of physical activity and function with a diverse cohort of UK adults in their 70s and 80s were used to investigate relative risk of all-cause mortality and diagnoses of new diseases over a 4-year period. Two hundred and forty older adults were randomly recruited from 12 general practices in urban and suburban areas of a city in the United Kingdom. Follow-up included 213 of the baseline sample. Socio-demographic variables, height and weight, and self-reported diagnosed diseases were recorded at baseline. Seven-day accelerometry was used to assess total physical activity, moderate-to-vigorous activity and sedentary time. A log recorded trips from home. Lower limb function was assessed using the Short Physical Performance Battery. Medical records were accessed on average 50 months post baseline, when new diseases and deaths were recorded. ANOVAs were used to assess socio-demographic, physical activity and lower limb function group differences in diseases at baseline and new diseases during follow-up. Regression models were constructed to assess the prospective associations between physical activity and function with mortality and new disease. For every 1,000 steps walked per day, the risk of mortality was 36% lower (hazard ratios 0.64, 95% confidence interval (CI) 0.44-0.91, P=0.013). Low levels of moderate-to-vigorous physical activity (incident rate ratio (IRR) 1.67, 95% CI 1.04-2.68, P=0.030) and low frequency of trips from home (IRR 1.41, 95% CI 0.98-2.05, P=0.045) were associated with diagnoses of more new diseases. Physical activity should be supported for adults in their 70s and 80s, as it is associated with reduced risk of mortality and new disease development. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.
Chrysohoou, C; Panagiotakos, D B; Pitsavos, C; Skoumas, J; Toutouza, M; Papaioannou, I; Stefanadis, C
2010-06-01
We aimed to evaluate the association between renal function and various cardiovascular disease (CVD) risk factors, as well as 5-year incidence of CVD, in a sample of CVD free adults. (i) Cross-sectional information from n = 1975. Greek men and women (>18 years) without CVD and hypertension at baseline examination and (ii) 5-year (2001-06) survival data from n = 2101 individuals without CVD at baseline, all participants in the ATTICA study, were analysed in this work. Kidney function was quantified by the baseline estimated creatinine clearance rate (C(cr)), using the Cockcroft-Gault formula and the National Kidney Foundation recommendations. Outcome of interest was the development of CVD that was defined according to WHO-ICD-10 criteria. At baseline, the prevalence of moderate-to-severe renal dysfunction (i.e. C(cr) < 60) was 2.8% in males and 7.7% in females. Physical activity status, cigarette smoking, hypercholesterolemia and homocysteine levels and greater adherence to the Mediterranean diet were inversely associated with C(cr) rate (P < 0.05), while no association was found with history of diabetes. During the 5-year follow-up, people with moderate-to-severe renal dysfunction as compared with normal, had 3.21 times higher CVD risk [95% confidence interval (CI) 1.98-5.19], after adjusting for history of hypertension (hazard ratio = 2.15, 95% CI 1.48-3.11), hypercholesterolemia (1.37, 0.98-1.98), diabetes (3.28, 2.15-5.00), smoking habits (0.89, 0.60-1.32) and physical activity status (0.86, 0.56-1.21). Renal function seems to be associated with the levels of lifestyle and bio-clinical CVD risk factors and contribute to the long-term incidence of cardiac events. Public health care practitioners should take into account renal function in better preventing the burden of CVD at individual, and population level, as well.
Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun
2017-01-01
Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093
Functions and requirements for tank farm restoration and safe operations, Project W-314. Revision 3
DOE Office of Scientific and Technical Information (OSTI.GOV)
Garrison, R.C.
1995-02-01
This Functions and Requirements document (FRD) establishes the basic performance criteria for Project W-314, in accordance with the guidance outlined in the letter from R.W. Brown, RL, to President, WHC, ``Tank Waste Remediation System (TWRS) Project Documentation Methodology,`` 94-PRJ-018, dated 3/18/94. The FRD replaces the Functional Design Criteria (FDC) as the project technical baseline documentation. Project W-314 will improve the reliability of safety related systems, minimize onsite health and safety hazards, and support waste retrieval and disposal activities by restoring and/or upgrading existing Tank Farm facilities and systems. The scope of Project W-314 encompasses the necessary restoration upgrades of themore » Tank Farms` instrumentation, ventilation, electrical distribution, and waste transfer systems.« less
Boyle, Patricia A; Buchman, Aron S; Wilson, Robert S; Leurgans, Sue E; Bennett, David A
2010-02-01
To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI). Prospective, observational cohort study. Approximately 40 retirement communities across the Chicago metropolitan area. More than 750 older persons without cognitive impairment at baseline. Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition. During up to 12 years of annual follow-up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one-unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27-2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities). Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.
Serum Urate at Trial Entry and ALS Progression in EMPOWER
O'Reilly, Éilis J.; Liu, Dawei; Johns, Donald R.; Cudkowicz, Merit E.; Paganoni, Sabrina; Schwarzschild, Michael A.; Leitner, Melanie; Ascherio, Alberto
2017-01-01
Objective Determine whether serum urate predicts ALS progression. Methods The study population comprised adult participants of EMPOWER (n=942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. Outcomes Combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results In women there was not a significant relation between urate and outcomes. In men, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend=0.04; and hazard ratio for death was 0.60 with p for trend=0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dL) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval: 0.47 to 0.95). Conclusion These findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate. PMID:27677562
“Smooth” Semiparametric Regression Analysis for Arbitrarily Censored Time-to-Event Data
Zhang, Min; Davidian, Marie
2008-01-01
Summary A general framework for regression analysis of time-to-event data subject to arbitrary patterns of censoring is proposed. The approach is relevant when the analyst is willing to assume that distributions governing model components that are ordinarily left unspecified in popular semiparametric regression models, such as the baseline hazard function in the proportional hazards model, have densities satisfying mild “smoothness” conditions. Densities are approximated by a truncated series expansion that, for fixed degree of truncation, results in a “parametric” representation, which makes likelihood-based inference coupled with adaptive choice of the degree of truncation, and hence flexibility of the model, computationally and conceptually straightforward with data subject to any pattern of censoring. The formulation allows popular models, such as the proportional hazards, proportional odds, and accelerated failure time models, to be placed in a common framework; provides a principled basis for choosing among them; and renders useful extensions of the models straightforward. The utility and performance of the methods are demonstrated via simulations and by application to data from time-to-event studies. PMID:17970813
Tertinger, D A; Greene, B F; Lutzker, J R
1984-01-01
Parents may be charged with child abuse or neglect or both on the basis of a variety of circumstances. Child neglect, for example, is often documented when caseworkers observe that the family's home itself is so poorly kept that it presents an environment in which young children have ready access to lethal hazards such as poisons, uncovered wall outlets, and firearms. In this study, we describe the development of a Home Accident Prevention Inventory (HAPI) which was validated and used to assess hazards in the homes of several families under state protective service for child abuse and neglect. The HAPI included five categories of hazards: fire and electrical, mechanical-suffocation, ingested object suffocation, firearms, and solid/liquid poisons. Following the collection of baseline data, parents were presented with a treatment package that included instructions and demonstrations on making hazards inaccessible to children, plus feedback regarding the number and location of hazards in the home. The multiple-baseline design across hazardous categories in each family's home showed that the package resulted in decreases in the number of these accessible hazards. These improvements were maintained over an extended period of unannounced follow-up checks. This research provides a model for the development and assessment of an area previously unexamined in the child abuse and neglect literature. PMID:6735949
Teaching Preschool Children to Avoid Poison Hazards
ERIC Educational Resources Information Center
Dancho, Kelly A.; Thompson, Rachel H.; Rhoades, Melissa M.
2008-01-01
We evaluated the effectiveness of group safety training and in situ feedback and response interruption to teach preschool children to avoid consuming potentially hazardous substances. Three children ingested ambiguous substances during a baited baseline assessment condition and continued to ingest these substances following group safety training.…
1996-05-01
no hazardous substances, regulated by the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), and no petroleum products ...Guidebook, Fall 1993, are as follows: 1. Areas where no storage, release or disposal of hazardous substances orpetroleum products has occurred...including no migration of these substances from adjacent areas) [white] S2. Areas where only storage of hazardous substances or petroleum products has
49 CFR 192.921 - How is the baseline assessment to be conducted?
Code of Federal Regulations, 2010 CFR
2010-10-01
...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Gas... the covered pipeline segments for the baseline assessment according to a risk analysis that considers...
DOT National Transportation Integrated Search
2003-10-29
The Beta Test and Baseline Data Collection efforts ensured that the test technologies would successfully operate during the field operational test (FOT) in the designed scenario configurations. These efforts also ensured that FOT systems would succes...
Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A
2012-10-01
Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Observational cohort study. 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Baseline estimated glomerular filtration rate (eGFR). Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m(2) for >3 months) in Cox proportional hazards and competing-risk regression models. Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m(2). Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m(2) remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m(2) was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m(2) and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m(2). The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Baseline Predictors of Missed Visits in the Look AHEAD Study
Fitzpatrick, Stephanie L.; Jeffery, Robert; Johnson, Karen C.; Roche, Cathy C.; Van Dorsten, Brent; Gee, Molly; Johnson, Ruby Ann; Charleston, Jeanne; Dotson, Kathy; Walkup, Michael P.; Hill-Briggs, Felicia; Brancati, Frederick L.
2013-01-01
Objective To identify baseline attributes associated with consecutively missed data collection visits during the first 48 months of Look AHEAD—a randomized, controlled trial in 5145 overweight/obese adults with type 2 diabetes designed to determine the long-term health benefits of weight loss achieved by lifestyle change. Design and Methods The analyzed sample consisted of 5016 participants who were alive at month 48 and enrolled at Look AHEAD sites. Demographic, baseline behavior, psychosocial factors, and treatment randomization were included as predictors of missed consecutive visits in proportional hazard models. Results In multivariate Cox proportional hazard models, baseline attributes of participants who missed consecutive visits (n=222) included: younger age ( Hazard Ratio [HR] 1.18 per 5 years younger; 95% Confidence Interval 1.05, 1.30), higher depression score (HR 1.04; 1.01, 1.06), non-married status (HR 1.37; 1.04, 1.82), never self-weighing prior to enrollment (HR 2.01; 1.25, 3.23), and randomization to minimal vs. intensive lifestyle intervention (HR 1.46; 1.11, 1.91). Conclusions Younger age, symptoms of depression, non-married status, never self-weighing, and randomization to minimal intervention were associated with a higher likelihood of missing consecutive data collection visits, even in a high-retention trial like Look AHEAD. Whether modifications to screening or retention efforts targeted to these attributes might enhance long-term retention in behavioral trials requires further investigation. PMID:23996977
Kim, Mimi; Adams-Campbell, Lucile L; Caan, Bette J; Chlebowski, Rowan T; Neuhouser, Marian L; Shikany, James M; Rohan, Thomas E
2009-01-01
Background: Prospective studies have examined the association of serum and plasma carotenoids and micronutrients and breast cancer; however, to date, studies have only assessed exposure at one point in time. Objective: This study analyzed baseline and repeated serum measurements of carotenoids, retinol, and tocopherols to assess their associations with postmenopausal breast cancer risk. Design: Serum concentrations of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, α-tocopherol, and γ-tocopherol were measured in a 6% sample of women in the Women's Health Initiative clinical trials at baseline and at years 1, 3, and 6 and in a 1% sample of women in the observational study at baseline and at year 3. The association of baseline compounds and breast cancer risk was estimated by Cox proportional hazards models. In addition, repeated measurements were analyzed as time-dependent covariates. Of 5450 women with baseline measurements, 190 incident cases of breast cancer were ascertained over a median of 8.0 y of follow-up. Results: After multivariable adjustment, risk of invasive breast cancer was inversely associated with baseline serum α-carotene concentrations (hazard ratio for highest compared with the lowest tertile: 0.55; 95% CI: 0.34, 0.90; P = 0.02) and positively associated with baseline lycopene (hazard ratio: 1.47; 95% CI: 0.98, 2.22; P = 0.06). Analysis of repeated measurements indicated that α-carotene and β-carotene were inversely associated with breast cancer and that γ-tocopherol was associated with increased risk. Conclusions: The present study, which was the first to assess repeated measurements of serum carotenoids and micronutrients in relation to breast cancer, adds to the evidence of an inverse association of specific carotenoids with breast cancer. The positive associations observed for lycopene and γ-tocopherol require confirmation. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:19474140
Circulating endothelial progenitor cells and cardiovascular outcomes.
Werner, Nikos; Kosiol, Sonja; Schiegl, Tobias; Ahlers, Patrick; Walenta, Katrin; Link, Andreas; Böhm, Michael; Nickenig, Georg
2005-09-08
Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined. The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes. A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes. The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk. Copyright 2005 Massachusetts Medical Society.
Mulenga, Lloyd B.; Kruse, Gina; Lakhi, Shabir; Cantrell, Ronald A.; Reid, Stewart E.; Zulu, Isaac; Stringer, Elizabeth M.; Krishnasami, Zipporah; Mwinga, Alwyn; Saag, Michael S.; Stringer, Jeffrey S. A.; Chi, Benjamin H.
2009-01-01
Objective To examine the association between baseline renal insufficiency and mortality among adults initiating antiretroviral therapy (ART) in urban African setting. Design Open cohort evaluation Methods We examined mortality according to baseline renal function among adults initiating ART in Lusaka, Zambia. Renal function was assessed by the Cockcroft-Gault method, the Modification of Diet in Renal Disease (MDRD) equation, and serum creatinine. Results From April 2004 to September 2007, 25,779 individuals started ART with an available creatinine measurement at baseline. When creatinine clearance was calculated by the Cockcroft-Gault method, 8,456 (33.5%) had renal insufficiency: 73.5% were mild (60-89 mL/min), 23.4% moderate (30-59 mL/min), and 3.1% severe (<30 mL/min). Risk for mortality at or before 90 days was elevated for those with mildly (adjusted hazard ratio [AHR]=1.7; 95%CI=1.5-1.9), moderately (AHR=2.3; 95%CI=2.0-2.7), and severely (AHR=4.1; 95%CI=3.1-5.5) reduced creatinine clearance. Mild (AHR=1.4; 95%CI=1.2-1.6), moderate (AHR=1.9; 95%CI=1.5-2.3), and severe (AHR=3.6; 95%CI=2.4-5.5) insufficiency were also associated with increased mortality after 90 days, when compared to those with normal renal function. Trends were similar when renal function was estimated with MDRD or serum creatinine. Conclusions Renal insufficiency at time of ART initiation was prevalent and associated with increased mortality risk among adults in this population. These results have particular relevance for settings like Zambia, where tenofovir - a drug with known nephrotoxicity - has been adopted as part of first-line therapy. This emphasizes the need for resource-appropriate screening algorithms for renal disease, both as part of ART eligibility and pre-treatment assessment. PMID:18753939
Shah, Ravi V; Murthy, Venkatesh L; Colangelo, Laura A; Reis, Jared; Venkatesh, Bharath Ambale; Sharma, Ravi; Abbasi, Siddique A; Goff, David C; Carr, J Jeffrey; Rana, Jamal S; Terry, James G; Bouchard, Claude; Sarzynski, Mark A; Eisman, Aaron; Neilan, Tomas; Das, Saumya; Jerosch-Herold, Michael; Lewis, Cora E; Carnethon, Mercedes; Lewis, Gregory D; Lima, Joao A C
2016-01-01
Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear. To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
Sedman, R M; Polisini, J M; Esparza, J R
1994-01-01
Potential public health effects associated with exposure to metal emissions from hazardous waste incinerators through noninhalation pathways were evaluated. Instead of relying on modeling the movement of toxicants through various environmental media, an approach based on estimating changes from baseline levels of exposure was employed. Changes in soil and water As, Cd, Hg, Pb, Cr, and Be concentrations that result from incinerator emissions were first determined. Estimates of changes in human exposure due to direct contact with shallow soil or the ingestion of surface water were then ascertained. Projected changes in dietary intakes of metals due to incinerator emissions were estimated based on changes from baseline dietary intakes that are monitored in U.S. Food and Drug Administration total diet studies. Changes from baseline intake were deemed to be proportional to the projected changes in soil or surface water metal concentrations. Human exposure to metals emitted from nine hazardous waste incinerators were then evaluated. Metal emissions from certain facilities resulted in tangible human exposure through noninhalation pathways. However, the analysis indicated that the deposition of metals from ambient air would result in substantially greater human exposure through noninhalation pathways than the emissions from most of the facilities. PMID:7925180
Jani, Bhautesh Dinesh; Cavanagh, Jonathan; Barry, Sarah J E; Der, Geoff; Sattar, Naveed; Mair, Frances S
2016-10-01
The authors studied the joint effect of blood pressure (BP) and depression on the risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35,537 patients with coronary heart disease, diabetes, or stroke underwent depression screening and BP measurement recorded concurrently. The authors used Cox's proportional hazards to calculate risk of major adverse cardiovascular event (MACE; myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. A total of 11% (3939) had experienced a MACE within 4 years. Patients with very high systolic BP (160-240 mm Hg; hazard ratio, 1.28) and depression (hazard ratio, 1.22) at baseline had significantly higher adjusted risk. Depression had a significant interaction with systolic BP in risk prediction (P=.03). Patients with a combination of high systolic BP and depression at baseline had 83% higher adjusted risk of MACE, as compared with patients with reference systolic BP without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of systolic BP. © 2016 The Authors. The Journal of Clinical Hypertension Published by Wiley Periodicals, Inc.
Causal Mediation Analysis of Survival Outcome with Multiple Mediators.
Huang, Yen-Tsung; Yang, Hwai-I
2017-05-01
Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.
Fujishiro, Kaori; Diez Roux, Ana V; Landsbergis, Paul; Kaufman, Joel D; Korcarz, Claudia E; Stein, James H
2015-01-01
Objectives The role of occupation in the development of cardiovascular disease (CVD) remains a topic of research because few studies have examined longitudinal associations, and because occupation can be an indicator of socioeconomic position (SEP) and a proxy for hazard exposure. This study examines associations of occupational category as an SEP marker and selected occupational exposures with progression of the subclinical carotid artery disease. Methods A community-based, multiethnic sample (n=3109, mean age=60.2) provided subclinical CVD measures at least twice at three data collection points (mean follow-up=9.4 years). After accounting for demographic characteristics, SEP, and traditional CVD risk factors, we modelled common carotid intima-media thickness, carotid plaque scores, and carotid plaque shadowing as a function of occupational category, physical hazard exposure, physical activity on the job, interpersonal stress, job control and job demands. These job characteristics were derived from the Occupational Resource Network (O*NET). Random coefficient models were used to account for repeated measures and time-varying covariates. Results There were a few statistically significant associations at baseline. After all covariates were included in the model, men in management, office/sales, service and blue-collar jobs had 28–44% higher plaque scores than professionals at baseline (p=0.001). Physically hazardous jobs were positively associated with plaque scores among women (p=0.014). However, there were no significant longitudinal associations between any of the occupational characteristics and any of the subclinical CVD measures. Conclusions There was little evidence that the occupational characteristics examined in this study accelerated the progression of subclinical CVD. PMID:25217203
The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.
Merlo, Marco; Gobbo, Marco; Stolfo, Davide; Losurdo, Pasquale; Ramani, Federica; Barbati, Giulia; Pivetta, Alberto; Di Lenarda, Andrea; Anzini, Marco; Gigli, Marta; Pinamonti, Bruno; Sinagra, Gianfranco
2016-09-01
In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Predictive validity of the AUDIT for hazardous alcohol consumption in recently released prisoners.
Thomas, Emma; Degenhardt, Louisa; Alati, Rosa; Kinner, Stuart
2014-01-01
This study aimed to assess the predictive validity of the Alcohol Use Disorders Identification Test (AUDIT) among adult prisoners with respect to hazardous drinking following release, and identify predictors of post-release hazardous drinking among prisoners screening positive for risk of alcohol-related harm on the AUDIT. Data came from a survey-based longitudinal study of 1325 sentenced adult prisoners in Queensland, Australia. Baseline interviews were conducted pre-release with follow-up at 3 and 6 months post-release. We calculated sensitivity, specificity and area under the receiver operating characteristic (AUROC) to quantify the predictive validity of the AUDIT administered at baseline with respect to post-release hazardous drinking. Other potential predictors of hazardous drinking were measured by self-report and their association with the outcome was examined using logistic regression. At a cut-point of 8 or above, sensitivity of the AUDIT with respect to hazardous drinking at 3-month follow-up was 81.0% (95%CI: 77.9-84.6%) and specificity was 65.6% (95%CI: 60.6-70.3%). The AUROC was 0.78 (95%CI: 0.75-0.81), indicating moderate accuracy. Among those scoring 8 or above, high expectations to drink post-release (AOR: 2.49; 95%CI: 1.57-3.94) and past amphetamine-type stimulant (ATS) use (AOR: 1.64; 95%CI: 1.06-2.56) were significantly associated with hazardous drinking at 3 months post-release. Results were similar at 6 months. Among adult prisoners in our sample, pre-release AUDIT scores predicted hazardous drinking six months after release with acceptable accuracy, sensitivity and specificity. Among prisoners screening positive on the AUDIT, expectations of post-release drinking and ATS use are potential targets for intervention to reduce future hazardous drinking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Saulnier, Pierre-Jean; Gand, Elise; Velho, Gilberto; Mohammedi, Kamel; Zaoui, Philippe; Fraty, Mathilde; Halimi, Jean Michel; Roussel, Ronan; Ragot, Stéphanie; Hadjadj, Samy
2017-03-01
We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA 1c , blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes. © 2017 by the American Diabetes Association.
Giugliani, Roberto; Lampe, Christina; Guffon, Nathalie; Ketteridge, David; Leão-Teles, Elisa; Wraith, James E; Jones, Simon A; Piscia-Nichols, Cheri; Lin, Ping; Quartel, Adrian; Harmatz, Paul
2014-08-01
Mucopolysaccharidosis VI (MPS VI) is a clinically heterogeneous and progressive disorder with multiorgan manifestations caused by deficient N-acetylgalactosamine-4-sulfatase activity. A cross-sectional Survey Study in individuals (n = 121) affected with MPS VI was conducted between 2001 and 2002 to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of disease. We conducted a Resurvey Study (ClinicalTrials.gov: NCT01387854) to obtain 10-year follow-up data, including medical histories and clinical assessments (n = 59), and survival status over 12 years (n = 117). Patients received a mean (SD) of 6.8 (2.2) years of galsulfase ERT between baseline (Survey Study) and follow-up. ERT patients increased in height by 20.4 cm in the 4-7-year-old baseline age group and by 16.8 cm in the 8-12-year-old baseline age group. ERT patients <13 years-old demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 sec (FEV1) by 55%, and those ≥13 years-old increased FVC by 12.8% and maintained FEV1. Patients with >200 µg/mg baseline uGAG levels increased FVC by 48% in the <13-year-old baseline age group and by 15% in the ≥13-year-old baseline age group. ERT patients who completed the 6-min walk test demonstrated a mean (SD) increase of 65.7 (100.6) m. Cardiac outcomes did not significantly improve or worsen. Observed mortality rate among naïve patients was 50% (7/14) and 16.5% (17/103) in the ERT group (unadjusted hazard ratio, 0.24; 95% CI, 0.10-0.59). Long-term galsulfase ERT was associated with improvements in pulmonary function and endurance, stabilized cardiac function and increased survival. © 2014 Wiley Periodicals, Inc.
Gray, Shelly L.; Boudreau, Robert M.; Newman, Anne B.; Studenski, Stephanie A.; Shorr, Ronald I; Bauer, Douglas C.; Simonsick, Eleanor M.; Hanlon, Joseph T
2012-01-01
Objective Angiotensin-converting enzyme (ACE) inhibitors and statin medications have been proposed as potential agents to prevent or delay physical disability; yet limited research has evaluated whether such use in older community dwelling adults is associated with a lower risk of incident mobility limitation. Design Longitudinal cohort study Setting Health, Aging and Body Composition (Health ABC) Participants 3055 participants who were well functioning at baseline (e.g., no mobility limitations). Measurements Summated standardized daily doses (low, medium and high) and duration of ACE inhibitor and statin use was computed. Mobility limitation (two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health status, and health behaviors. Results At baseline, ACE inhibitors and statins were used by 15.2% and 12.9%, respectively and both increased to over 25% by year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.82–1.09) nor statin use (multivariate HR 1.02; 95% CI 0.87–1.17) was associated with a lower risk for mobility limitation. Similar findings were seen in analyses examining dose- and duration-response relationships and sensitivity analyses restricted to those with hypertension. Conclusions These findings indicate that ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively do not lower risk of mobility limitation, an important life quality indicator. PMID:22092102
Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.
Morimoto, Sarah Shizuko; Gunning, Faith M; Kanellopoulos, Dora; Murphy, Christopher F; Klimstra, Sibel A; Kelly, Robert E; Alexopoulos, George S
2012-05-01
This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression. Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates. Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response. Copyright © 2011 John Wiley & Sons, Ltd.
Gray, Shelly L; Boudreau, Robert M; Newman, Anne B; Studenski, Stephanie A; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Hanlon, Joseph T
2011-12-01
To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Longitudinal cohort study. Health, Aging and Body Composition (Health ABC) study. Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.
Serum urate at trial entry and ALS progression in EMPOWER.
O'Reilly, ÉIlis J; Liu, Dawei; Johns, Donald R; Cudkowicz, Merit E; Paganoni, Sabrina; Schwarzschild, Michael A; Leitner, Melanie; Ascherio, Alberto
2017-02-01
Our objective was to determine whether serum urate predicts ALS progression. A study population comprised adult participants of EMPOWER (n = 942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. We measured outcomes by combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results showed that in females there was not a significant relation between urate and outcomes. In males, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend = 0.04; and hazard ratio for death was 0.60 with p for trend = 0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dl) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval 0.47-0.95). In conclusion, these findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate.
Saeed, Mohammed J; Olsen, Margaret A; Powderly, William G; Presti, Rachel M
2017-01-01
To investigate the association of diabetes with risk of decompensated cirrhosis in patients with chronic hepatitis C (CHC). Direct-acting antivirals are highly effective in treating CHC but very expensive. CHC patients at high risk of progression to symptomatic liver disease may benefit most from early treatment. We conducted a retrospective cohort study using the 2006 to 2013 Truven Health Analytics MarketScan Commercial Claims and Encounters database including inpatient, outpatient, and pharmacy claims from private insurers. CHC and cirrhosis were identified using ICD-9-CM diagnosis codes; baseline diabetes was identified by diagnosis codes or antidiabetic medications. CHC patients were followed to identify decompensated cirrhosis. Multivariable Cox proportional hazards regression was used to model the risk of decompensated cirrhosis by baseline cirrhosis. There were 75,805 CHC patients with median 1.9 years follow-up. A total of 10,317 (13.6%) of the CHC population had diabetes. The rates of decompensated cirrhosis per 1000 person-years were: 185.5 for persons with baseline cirrhosis and diabetes, 119.8 for persons with cirrhosis and no diabetes, 35.3 for persons with no cirrhosis and diabetes, and 17.1 for persons with no cirrhosis and no diabetes. Diabetes was associated with increased risk of decompensated cirrhosis in persons with baseline cirrhosis (adjusted hazard ratio=1.4; 95% confidence interval, 1.3-1.6) and in persons without baseline cirrhosis (adjusted hazard ratio=1.9; 95% confidence interval, 1.7-2.1). In a privately insured US population with CHC, the adjusted risk of decompensated cirrhosis was higher in diabetic compared with nondiabetic patients. Diabetes status should be included in prioritization of antiviral treatment.
Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza
2016-11-01
We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Bahorik, Amber L; Campbell, Cynthia I; Sterling, Stacy A; Leibowitz, Amy; Travis, Adam; Weisner, Constance M; Satre, Derek D
2018-01-01
This study examined whether marijuana use was associated with clinically problematic outcomes for patients with depression and alcohol use disorder (AUD). The sample consisted of 307 psychiatry outpatients with mild to severe depression and past 30-day hazardous drinking/drug use, who participated in a trial of substance use treatment. Participants were assessed for AUD based on DSM-IV criteria. Measures of marijuana use, depression symptoms, and functional status related to mental health were collected at baseline, 3, and 6 months. Differences in these outcomes were analyzed among patients with and without AUD using growth models, adjusting for treatment effects. Marijuana was examined as both an outcome (patterns of use) and a predictor (impact on depression and functioning). Forty percent used marijuana and about half the sample met AUD criteria. Fewer patients with AUD used marijuana than those without AUD at baseline. Over 6 months, the proportion of patients with AUD using marijuana increased compared to those without AUD. Patients with AUD using marijuana had greater depressive symptoms and worse functioning than those without AUD. These findings indicate that marijuana use is clinically problematic for psychiatry outpatients with depression and AUD. Addressing marijuana in the context of psychiatry treatment may help improve outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.
Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study.
Kamei, Keita; Konta, Tsuneo; Ichikawa, Kazunobu; Sato, Hiroko; Suzuki, Natsuko; Kabasawa, Asami; Suzuki, Kazuko; Hirayama, Atsushi; Shibata, Yoko; Watanabe, Tetsu; Kato, Takeo; Ueno, Yoshiyuki; Kayama, Takamasa; Kubota, Isao
2016-12-01
Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population. Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population. One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank P < 0.01), but not male subjects (P = 0.97). Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia (uric acid ≥7.0 mg/dL) was an independent risk factor for all-cause and cardiovascular mortality, respectively, in female [hazard ratio (HR) 5.92, 95 % confidence interval (CI) 2.10-14.6 for all-cause mortality, and HR 10.7, 95 % CI 1.76-50.2 for cardiovascular mortality], but not male subjects. Hyperuricemia was an independent risk for all-cause and cardiovascular mortality in female, but not among the male subjects in a community-based population.
Apolipoprotein E and mortality in African-Americans and Yoruba.
Lane, Kathleen A; Gao, Sujuan; Hui, Siu L; Murrell, Jill R; Hall, Kathleen S; Hendrie, Hugh C
2003-10-01
The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).
Apolipoprotein E and mortality in African-Americans and Yoruba
Lane, Kathleen A.; Gao, Sujuan; Hui, Siu L.; Murrell, Jill R.; Hall, Kathleen S.; Hendrie, Hugh C.
2011-01-01
The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE ε4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 ( hazard ratio: 2.00; 95% CI: 1.19–3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45–1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274). PMID:14646029
Chatterjee, Neal A; Shah, Ravi V; Murthy, Venkatesh L; Praestgaard, Amy; Shah, Sanjiv J; Ventetuolo, Corey E; Barr, R Graham; Kronmal, Richard; Lima, Joao A C; Bluemke, David A; Jerosch-Herold, Michael; Alonso, Alvaro; Kawut, Steven M
2017-01-01
Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61±10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. © 2017 American Heart Association, Inc.
Durheim, Michael T; Smith, Patrick J; Babyak, Michael A; Mabe, Stephanie K; Martinu, Tereza; Welty-Wolf, Karen E; Emery, Charles F; Palmer, Scott M; Blumenthal, James A
2015-03-01
The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.
Voss, Jameson D; Burnett, Daniel G; Olsen, Cara H; Haverkos, Harry W; Atkinson, Richard L
2014-09-01
Obesity is a public health priority, which also threatens national security. Adenovirus 36 (Adv36) increases adiposity in animals and Adv36 antibody status is associated with human obesity, but it is unknown whether infection predicts the development of human adiposity. The objective of the study was to assess infection status and subsequent weight gain. The study had a retrospective cohort design. The study was conducted at Air Force fitness testing and clinical encounters. PARTICIPANTS included Air Force male enlistees, aged 18-22 years, with a baseline body mass index (BMI) of 20-30 kg/m(2) followed up from enlistment (beginning in 1995) until 2012 or separation from the Air Force. EXPOSURE included Adv36 infection status at the time of entry. Follow-up BMI, the primary outcome, and diagnosis of overweight/obesity by the International Classification of Diseases, ninth revision V85.25+ and 278.0* series (secondary outcome) were recorded. The last recorded follow-up BMI was similar among infected and uninfected, 26.4 and 27.2 kg/m(2), respectively (P > .05). However, infected individuals had a higher hazard of a medical provider's diagnosis of overweight/obese over time (hazard ratio 1.8, 95% confidence interval 1.0-3.1, P = .04), adjusted for baseline BMI. Additionally, infected individuals who were lean at baseline (BMI of 22.5 kg/m(2)) had a 3.9 times greater hazard of developing an overweight/obese clinical diagnosis (95% confidence interval 1.5-9.7, P = .004) compared with uninfected lean individuals after adjusting for interaction (P = .03) between infection and baseline BMI. The presence of Adv36 antibodies was not associated with higher BMI at baseline or follow-up within this military population. However, being infected was associated with developing a clinical diagnosis of overweight/obesity, especially among those lean at baseline.
Using the Auditory Hazard Assessment Algorithm for Humans (AHAAH) Software, Beta Release W93e
2009-09-01
Hazard Assessment Algorithm for Humans (AHAAH) Does The AHAAH is an electro- acoustic model of the ear used to evaluate the hazard of impulse sounds...format is commonly used for recording music ; thus, these are typically stereo files and contain a “right” and a “left” channel as well as a header... acoustic data (sometimes deliberately induced in recording to maximize the digitizer’s dynamic range), it must be removed. When Set Baseline is
Desai, Rishi J; Franklin, Jessica M; Spoendlin-Allen, Julia; Solomon, Daniel H; Danaei, Goodarz; Kim, Seoyoung C
2018-01-01
Gout patients have a high burden of co-morbid conditions including diabetes mellitus (DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). We sought to evaluate the association between changes in serum uric acid (SUA) levels over time and the risk of incident DM, CVD, and renal function decline in gout patients. An observational cohort study was conducted among enrollees of private health insurance programs in the US between 2004 and 2015. Gout patients were included on the index date of a SUA measurement ≥6.8 mg/dl. The exposure of interest was cumulative change in SUA levels from baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for incident DM, incident CVD, and renal function decline (≥30% reduction in glomerular filtration rate) were derived using marginal structural models with stabilized inverse probability weights accounting for baseline confounders (age, gender, co-morbidities, co-medications) and time-varying confounders (serum creatinine, blood urea nitrogen, glycated hemoglobin). Among 26,341 patients with gout, the average age was 62, 75% were men, and the median baseline SUA was 8.6 mg/dl (interquartile range 7.7 to 9.5). The incidence rates/100 person-years (95% CI) were 1.63 (1.51-1.75) for DM, 0.77 (0.70-0.84) for CVD, and 4.32 (4.14-4.49) for renal function decline. The adjusted HR (95% CI) per 3 mg/dl reduction in SUA, corresponding on average to achieving the target level of <6 mg/dl in this population, was 1.04 (0.92-1.17) for DM, 1.07 (0.89-1.29) for CVD, and 0.85 (0.78-0.92) for renal function decline. Reduction in SUA in patients with gout may be associated with a reduced risk of renal function decline, but not with DM or CVD.
Yu, Edward; Papandreou, Christopher; Ruiz-Canela, Miguel; Guasch-Ferre, Marta; Clish, Clary B; Dennis, Courtney; Liang, Liming; Corella, Dolores; Fitó, Montserrat; Razquin, Cristina; Lapetra, José; Estruch, Ramón; Ros, Emilio; Cofán, Montserrat; Arós, Fernando; Toledo, Estefania; Serra-Majem, Lluis; Sorlí, José V; Hu, Frank B; Martinez-Gonzalez, Miguel A; Salas-Salvado, Jordi
2018-06-08
Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. Contrary to our hypothesis, baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. © 2018 American Association for Clinical Chemistry.
The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.
Silva, Jack P; Gorman, Richard A; Berger, Nicholas G; Tsai, Susan; Christians, Kathleen K; Clarke, Callisia N; Mogal, Harveshp; Gamblin, T Clark
2017-12-01
Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients. © 2017 Wiley Periodicals, Inc.
Renal Salvage with Renal Artery Stenting Improves Long-term Survival.
Modrall, J Gregory; Trimmer, Clayton; Tsai, Shirling; Kirkwood, Melissa L; Ali, Mujtaba; Rectenwald, John E; Timaran, Carlos H; Rosero, Eric B
2017-11-01
The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial cast doubt on the benefits of renal artery stenting (RAS). However, the outcomes for patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL Trial. We hypothesized that patients who experienced a significant improvement in renal function after RAS would have improved long-term survival, compared with patients whose renal function was not improved by stenting. This single-center retrospective study included 60 patients with stage 3 or worse CKD and renal artery occlusive disease who were treated with RAS for renal salvage. Patients were categorized as "responders" or "nonresponders" based on postoperative changes in estimated glomerular filtration rate (eGFR) after RAS. "Responders" were those patients with an improvement of at least 20% in eGFR over baseline; all others were categorized as "nonresponders." Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression was used to identify predictors of long-term survival. The median age of the cohort was 66 years (interquartile range [IQR], 60-73). Median preoperative eGFR was 34 mL/min/1.73 m 2 (IQR, 24-45). At late follow-up (median 35 months, IQR, 22-97 months), 16 of 60 patients (26.7%) were categorized as "responders" with a median increase in postoperative eGFR of 40% (IQR, 21-67). Long-term survival was superior for responders, compared with nonresponders (P = 0.046 by log-rank test). Cox proportional hazards regression identified improved renal function after RAS as the only significant predictor of increased long-term survival (hazard ratio = 0.235, 95% confidence interval = 0.075-0.733; P = 0.0126 for improved versus worsened renal function after RAS). Successful salvage of renal function by RAS is associated with improved long-term survival. These data provide an important counter argument to the prior negative clinical trials that found no benefit to RAS. Published by Elsevier Inc.
Debette-Gratien, Marilyne; Woillard, Jean-Baptiste; Picard, Nicolas; Sebagh, Mylène; Loustaud-Ratti, Véronique; Sautereau, Denis; Samuel, Didier; Marquet, Pierre
2016-10-01
This study investigated the influence of the CYP3A4*22, CYP3A5*3, and ABCB1 exons 12, 21, and 26 polymorphisms in donors and recipients on clinical outcomes and renal function in 170 liver transplant patients on cyclosporin A (CsA) or tacrolimus (Tac). Allelic discrimination assays were used for genotyping. Multivariate time-dependent Cox proportional hazard models, multiple linear regression using the generalized estimating equation and linear mixed-effect models were used for statistical analysis. Expression of CYP3A5 by either or both the donor and the recipient was significantly associated with lower Tac, but not CsA, dose-normalized trough levels. In the whole population, graft loss was only significantly associated with longer exposure to high calcineurin inhibitor (CNI) concentrations (hazard ratio, 6.93; 95% confidence interval, 2.13-22.55), P = 0.00129), whereas in the Tac subgroup, the risk of graft loss was significantly higher in recipient CYP3A5*1 expressers (hazard ratio, 3.39; 95% confidence interval, 1.52-7.58; P = 0.0028). Renal function was significantly associated with: (1) baseline modification of diet in renal disease (β = 0.51 ± 0.05; P < 0.0001); (2) duration of patient follow-up (per visit, β = -0.98 ± 0.22; P < 0.0001); and (3) CNI exposure (per quantile increase, β = -2.42 ± 0.59; P < 0.0001). No genetic factor was associated with patient survival, acute rejection, liver function test results, recurrence of viral or other initial liver disease, or renal function. This study confirms the effect of CYP3A5*3 on tacrolimus dose requirement in liver transplantation and shows unexpected associations between the type of, and exposure to, CNI and either chronic rejection or graft loss. None of the genetic polymorphisms studied had a noticeable impact on renal function degradation at 10 years.
Beddhu, Srinivasan; Chertow, Glenn M; Cheung, Alfred K; Cushman, William C; Rahman, Mahboob; Greene, Tom; Wei, Guo; Campbell, Ruth C; Conroy, Margaret; Freedman, Barry I; Haley, William; Horwitz, Edward; Kitzman, Dalane; Lash, James; Papademetriou, Vasilios; Pisoni, Roberto; Riessen, Erik; Rosendorff, Clive; Watnick, Suzanne G; Whittle, Jeffrey; Whelton, Paul K
2018-01-09
In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level ( P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062. © 2017 American Heart Association, Inc.
Nowrangi, Milap A.; Rosenberg, Paul B.; Leoutsakos, Jeannie-Marie S.
2017-01-01
Background There are relatively small but observable changes in functional ability in those without Mild cognitive impairment (MCI) or dementia. The present study seeks to understand whether these individuals go on to develop MCI or dementia by assessing the association between baseline Functional Activities Questionnaire (FAQ) and conversion independent and after adjustment for cognitive tests. Methods The NACC database was used to conduct the analysis of which 7,625 participants were initially identified as having more than one visit and who were cognitively normal at their first visit. Cox proportional hazards were used to fit three models that controlled for executive and non-executive cognitive domains. A similar model was used to assess the effect of FAQ subcategories on conversion. Results Of these individuals, 1,328 converted to either MCI or dementia by visit 10. Converters had a total visit 1 FAQ score significantly higher than non-converters indicating more functional impairment at baseline. After adjustment for cognitive tests, the association between visit 1 FAQ and subsequent conversion was not attenuated. Doing taxes, remembering dates, and traveling were individually identified as significant predictors of conversion. Conclusions The FAQ can be used as an indirect measure of functional ability and is associated with conversion to MCI or dementia. There is a selective and significant association between changes in financial ability and conversion that is in accordance with other research of financial capacity. PMID:27585497
McDermott, Mary M; Polonsky, Tamar S; Kibbe, Melina R; Tian, Lu; Zhao, Lihui; Pearce, William H; Gao, Ying; Guralnik, Jack M
2017-09-01
The objective of this study was to determine whether blacks with lower extremity peripheral artery disease (PAD) have faster functional decline than whites with PAD. Participants with ankle-brachial index <0.90 were identified from Chicago medical centers and observed longitudinally. Mobility impairment and the 6-minute walk were assessed at baseline and every 6 to 12 months. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or to walk ¼ mile without assistance. Of 1162 PAD participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711 PAD participants who walked 6 minutes continuously at baseline, black participants were more likely to become unable to walk 6 minutes continuously during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black race was associated with becoming unable to walk 6 minutes continuously, adjusting for age, sex, ankle-brachial index, comorbidities, and other confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022). This association was attenuated after adjustment for income and education (P = .229). Among 844 participants without baseline mobility impairment, black participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635 [25.8%]; log-rank, P = .009). Black race was associated with increased mobility loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence interval, 1.04-1.94; P = .028). This association was attenuated after additional adjustment for income and education (P = .392) and physical activity (P = .113). There were no racial differences in average annual declines in 6-minute walk, usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity. Black PAD patients have higher rates of mobility loss and becoming unable to walk for 6 minutes continuously. These differences appear related to racial differences in socioeconomic status and physical activity. Copyright © 2017 Society for Vascular Surgery. All rights reserved.
Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study.
Chiu, Tina H T; Pan, Wen-Harn; Lin, Ming-Nan; Lin, Chin-Lon
2018-03-09
Vegetarian diets are inversely associated with diabetes in Westerners but their impact on Asians-whose pathophysiology differ from Westerners-is unknown. We aim to investigate the association between a vegetarian diet, change in dietary patterns and diabetes risk in a Taiwanese Buddhist population. We prospectively followed 2918 non-smoking, non-alcohol drinking Buddhists free of diabetes, cancer, and cardiovascular diseases at baseline, for a median of 5 years, with 183 incident diabetes cases confirmed. Diet was assessed through a validated food frequency questionnaire at baseline and a simple questionnaire during follow-ups. Incident cases of diabetes were ascertained through follow-up questionnaires, fasting glucose and HbA1C. Stratified Cox Proportional Hazards Regression was used to assess the effect of diets on risk of diabetes. Consistent vegetarian diet was associated with 35% lower hazards (HR: 0.65, 95% CI: 0.46, 0.92), while converting from a nonvegetarian to a vegetarian pattern was associated with 53% lower hazards (HR: 0.47, 95% CI: 0.30, 0.71) for diabetes, comparing with nonvegetarians while adjusting for age, gender, education, physical activity, family history of diabetes, follow-up methods, use of lipid-lowering medications, and baseline BMI. Vegetarian diet and converting to vegetarian diet may protect against diabetes independent of BMI among Taiwanese.
Brenowitz, Willa D; Kukull, Walter A; Beresford, Shirley A A; Monsell, Sarah E; Williams, Emily C
2014-01-01
Social relationships are hypothesized to prevent or slow cognitive decline. We sought to evaluate associations between social relationships and mild cognitive impairment (MCI). Participants from the National Alzheimer's Coordinating Center database who were cognitively normal, aged 55 and older at baseline, and had at least 2 in-person visits (n=5335) were included. Multivariable Cox proportional hazard models evaluated the association between 4 social relationships at baseline (marital status, living situation, having children, and having siblings) and risk of developing MCI (on the basis of clinician diagnosis following established criteria). Primary models were adjusted for baseline demographics. Participants were followed, on average, for 3.2 years; 15.2% were diagnosed with MCI. Compared with married participants, risk of MCI was significantly lower for widowed participants (hazard ratio: 0.87; 95% confidence interval: 0.76, 0.99) but not for divorced/separated or never-married participants. Compared with living with a spouse/partner, risk of MCI was significantly higher for living with others (hazard ratio: 1.35; 95% confidence interval: 1.03, 1.77) but not for living alone. Risk of MCI was not associated with having children or having siblings. These results did not consistently identify social relationships as a strong risk factor for, or independent clinical predictor of, MCI.
Okin, Peter M; Kjeldsen, Sverre E; Devereux, Richard B
2018-04-01
The SPRINT study demonstrated that targeting systolic blood pressure (SBP) less than 120 mmHg was associated with lower cardiovascular event and mortality rates. In the LIFE study, however, a lower achieved SBP was associated with increased mortality. Mean baseline SBP in SPRINT was 140 mmHg and a third of the population had a baseline SBP 132 mmHg or less, raising the question of whether the lower baseline SBP in SPRINT could in part account for these differences. All-cause mortality during 4.8 ± 0.9 years follow-up was examined in relation to tertiles of achieved on-treatment average SBP in patients with baseline SBP of 25th percentile or less versus greater than 25th percentile value of 164 mmHg in 7998 nondiabetic hypertensive patients with ECG left ventricular hypertrophy randomly assigned to losartan-based or atenolol-based treatment. Average on-treatment SBP less than 142 mmHg (lowest tertile) and average SBP 142 mmHg to less than 152 mmHg (middle tertile) were compared with average SBP at least 152 mmHg (highest tertile and reference group). In the overall population, there was a significant interaction between baseline SBP 164 mmHg or less and average on-treatment SBP less than 142 mmHg in Cox analysis (χ = 15.48, P < 0.001). Among patients with baseline SBP greater than 164 mmHg, in multivariate Cox analyses adjusting for other potential predictors of mortality and a propensity score for having baseline SBP 164 mmHg or less and compared with average on-treatment SBP at least 152 mmHg, average on-treatment SBP less than 142 mmHg was associated with 32% higher mortality (hazard ratio 1.32, 95% CI 1.01-1.65), whereas average SBP of 142 mmHg to less than 152 mmHg was associated with 24% lower mortality (hazard ratio 0.76, 95% CI 0.59-0.98). In contrast, among patients with baseline SBP 164 mmHg or less, both average on-treatment SBP less than 142 mmHg (hazard ratio 0.60, 95% CI 0.36-0.99) and average SBP of 142 mmHg to less than 152 mmHg (hazard ratio 0.51, 95% CI 0.30-0.89) were associated with significantly lower mortality compared with average SBP of at least 152 mmHg. Achievement of an average SBP less than 142 mmHg was associated with reduced mortality in patients with baseline SBP 164 mmHg or less but with increased mortality in those with higher baseline SBP in LIFE. These findings suggest that the lower mortality associated with a lower targeted SBP in SPRINT may not be applicable to patients with considerably higher baseline SBP than SPRINT patients. Further study is necessary to better understand these findings. http://clinicaltrials.gov/ct/show/NCT00338260?order=1.
Going beyond the flood insurance rate map: insights from flood hazard map co-production
NASA Astrophysics Data System (ADS)
Luke, Adam; Sanders, Brett F.; Goodrich, Kristen A.; Feldman, David L.; Boudreau, Danielle; Eguiarte, Ana; Serrano, Kimberly; Reyes, Abigail; Schubert, Jochen E.; AghaKouchak, Amir; Basolo, Victoria; Matthew, Richard A.
2018-04-01
Flood hazard mapping in the United States (US) is deeply tied to the National Flood Insurance Program (NFIP). Consequently, publicly available flood maps provide essential information for insurance purposes, but they do not necessarily provide relevant information for non-insurance aspects of flood risk management (FRM) such as public education and emergency planning. Recent calls for flood hazard maps that support a wider variety of FRM tasks highlight the need to deepen our understanding about the factors that make flood maps useful and understandable for local end users. In this study, social scientists and engineers explore opportunities for improving the utility and relevance of flood hazard maps through the co-production of maps responsive to end users' FRM needs. Specifically, two-dimensional flood modeling produced a set of baseline hazard maps for stakeholders of the Tijuana River valley, US, and Los Laureles Canyon in Tijuana, Mexico. Focus groups with natural resource managers, city planners, emergency managers, academia, non-profit, and community leaders refined the baseline hazard maps by triggering additional modeling scenarios and map revisions. Several important end user preferences emerged, such as (1) legends that frame flood intensity both qualitatively and quantitatively, and (2) flood scenario descriptions that report flood magnitude in terms of rainfall, streamflow, and its relation to an historic event. Regarding desired hazard map content, end users' requests revealed general consistency with mapping needs reported in European studies and guidelines published in Australia. However, requested map content that is not commonly produced included (1) standing water depths following the flood, (2) the erosive potential of flowing water, and (3) pluvial flood hazards, or flooding caused directly by rainfall. We conclude that the relevance and utility of commonly produced flood hazard maps can be most improved by illustrating pluvial flood hazards and by using concrete reference points to describe flooding scenarios rather than exceedance probabilities or frequencies.
Subjective Sleep Quality Deteriorates Prior to Development of Painful Temporomandibular Disorder
Sanders, Anne E.; Akinkugbe, Aderonke A.; Bair, Eric; Fillingim, Roger B.; Greenspan, Joel D.; Ohrbach, Richard; Dubner, Ronald; Maixner, William; Slade, Gary D.
2016-01-01
There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the OPPERA prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every three months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n=220) and matched TMD-free controls (n=193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio=1.73, 95% confidence limits: 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, non-pain facial symptoms and demographics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity nor change in pain sensitivity. PMID:26902644
Meteorological Support at the Savanna River Site
DOE Office of Scientific and Technical Information (OSTI.GOV)
Addis, Robert P.
2005-10-14
The Department of Energy (DOE) operates many nuclear facilities on large complexes across the United States in support of national defense. The operation of these many and varied facilities and processes require meteorological support for many purposes, including: for routine operations, to respond to severe weather events, such as lightning, tornadoes and hurricanes, to support the emergency response functions in the event of a release of materials to the environment, for engineering baseline and safety documentation, as well as hazards assessments etc. This paper describes a program of meteorological support to the Savannah River Site, a DOE complex located inmore » South Carolina.« less
Cochrane, Shannon K; Chen, Shyh-Huei; Fitzgerald, Jodi D; Dodson, John A; Fielding, Roger A; King, Abby C; McDermott, Mary M; Manini, Todd M; Marsh, Anthony P; Newman, Anne B; Pahor, Marco; Tudor-Locke, Catrine; Ambrosius, Walter T; Buford, Thomas W
2017-12-02
Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P =0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [ P =0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [ P =0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [ P =0.002]) were significantly associated with lower cardiovascular event rates. Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Christensen, Bianca; Qin, Zijian; Byrd, Desiree A; Yu, Fang; Morgello, Susan; Gelman, Benjamin B; Moore, David J; Grant, Igor; Singer, Elyse J; Fox, Howard S; Baccaglini, Lorena
2017-10-01
With the transition of HIV infection from an acute to a chronic disease after the introduction of antiretroviral medications, there has been an increased focus on long-term neurocognitive and other functional outcomes of HIV patients. Thus, we assessed factors, particularly history of a substance use disorder, associated with time to loss of measures of physical or mental independence among HIV-positive individuals. Data were obtained from the National NeuroAIDS Tissue Consortium. Kaplan-Meier and Cox proportional hazards regression analyses were used to estimate the time since HIV diagnosis to loss of independence, and to identify associated risk factors. HIV-positive participants who self-identified as physically (n = 698) or mentally (n = 616) independent on selected activities of daily living at baseline were eligible for analyses. A history of substance use disorder was associated with a higher hazard of loss of both physical and mental independence [adjusted hazard ratio (HR) = 1.71, 95% confidence interval (95% CI): 1.07-2.78; adjusted HR = 1.67, 95% CI: 1.11-2.52, respectively]. After adjusting for substance use disorder and other covariates, older age at diagnosis and female gender were associated with higher hazards of loss of both physical and mental independence, non-white participants had higher hazards of loss of physical independence, whereas participants with an abnormal neurocognitive diagnosis and fewer years of education had higher hazards of loss of mental independence. In summary, history of substance use disorder was associated with loss of measures of both physical and mental independence. The nature of this link and the means to prevent such loss of independence need further investigation.
Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?
Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J
2016-12-01
The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.
Semiparametric Time-to-Event Modeling in the Presence of a Latent Progression Event
Rice, John D.; Tsodikov, Alex
2017-01-01
Summary In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood–based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set. PMID:27556886
Semiparametric time-to-event modeling in the presence of a latent progression event.
Rice, John D; Tsodikov, Alex
2017-06-01
In cancer research, interest frequently centers on factors influencing a latent event that must precede a terminal event. In practice it is often impossible to observe the latent event precisely, making inference about this process difficult. To address this problem, we propose a joint model for the unobserved time to the latent and terminal events, with the two events linked by the baseline hazard. Covariates enter the model parametrically as linear combinations that multiply, respectively, the hazard for the latent event and the hazard for the terminal event conditional on the latent one. We derive the partial likelihood estimators for this problem assuming the latent event is observed, and propose a profile likelihood-based method for estimation when the latent event is unobserved. The baseline hazard in this case is estimated nonparametrically using the EM algorithm, which allows for closed-form Breslow-type estimators at each iteration, bringing improved computational efficiency and stability compared with maximizing the marginal likelihood directly. We present simulation studies to illustrate the finite-sample properties of the method; its use in practice is demonstrated in the analysis of a prostate cancer data set. © 2016, The International Biometric Society.
Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie
2015-12-01
♦ As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.
Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie
2015-01-01
♦ Background: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ Methods: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ Results: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 – 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 – 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 – 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 – 0.94) and 0.39 (95% CI 0.20 – 0.75), respectively. ♦ Conclusions: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. PMID:26224791
Szeto, Cheuk-Chun; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Chung, Sebastian; Yu, Vincent; Cheng, Phyllis Mei-Shan; Leung, Chi-Bon; Law, Man-Ching; Li, Philip Kam-Tao
2015-01-01
♦ Background: Residual renal function (RRF) is an important prognostic indicator in continuous ambulatory peritoneal dialysis (CAPD) patients. We determined the predictors of RRF loss in a cohort of incident CAPD patients. ♦ Methods: We reviewed the record of 645 incident CAPD patients. RRF loss is represented by the slope of decline of residual glomerular filtration rate (GFR) as well as the time to anuria. ♦ Results: The average rate of residual GFR decline was -0.083 ± 0.094 mL/min/month. The rate of residual GFR decline was faster with a higher proteinuria (r = -0.506, p < 0.0001) and baseline residual GFR (r = -0.560, p < 0.0001). Multivariate analysis showed that proteinuria, baseline residual GFR, and the use of diuretics were independent predictors of residual GFR decline. Cox proportional hazard model showed that proteinuria, glucose exposure, and the number of peritonitis episodes were independent predictors of progression to anuria, while a higher baseline GFR was protective. Each 1 g/day of proteinuria is associated with a 13.2% increase in the risk of progressing to anuria, each 10 g/day higher glucose exposure is associated with a 2.5% increase in risk, while each peritonitis episode confers a 3.8% increase in risk. ♦ Conclusions: Our study shows that factors predicting the loss of residual solute clearance and urine output are different. Proteinuria, baseline residual GFR, and the use of diuretics are independently related to the rate of RRF decline in CAPD patients, while proteinuria, glucose exposure, and the number of peritonitis episodes are independent predictors for the development of anuria. The role of anti-proteinuric therapy and measures to prevent peritonitis episodes in the preservation of RRF should be tested in future studies. PMID:24497594
Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards
NASA Astrophysics Data System (ADS)
Ham, H. J.; Lee, S.; Choi, S. H.; Yun, W. S.
2015-12-01
Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards Hee Jung Ham1, Seung-Hun Choi1, Woo-Seok Yun1, Sungsu Lee2 1Department of Architectural Engineering, Kangwon National University, Korea 2Division of Civil Engineering, Chungbuk National University, Korea ABSTRACT In this study, fragility functions are developed to estimate expected volcanic ash damages of the agricultural sector in Korea. The fragility functions are derived from two approaches: 1) empirical approach based on field observations of impacts to agriculture from the 2006 eruption of Merapi volcano in Indonesia and 2) the FOSM (first-order second-moment) analytical approach based on distribution and thickness of volcanic ash observed from the 1980 eruption of Mt. Saint Helens and agricultural facility specifications in Korea. Fragility function to each agricultural commodity class is presented by a cumulative distribution function of the generalized extreme value distribution. Different functions are developed to estimate production losses from outdoor and greenhouse farming. Seasonal climate influences vulnerability of each agricultural crop and is found to be a crucial component in determining fragility of agricultural commodities to an ash fall. In the study, the seasonality coefficient is established as a multiplier of fragility function to consider the seasonal vulnerability. Yields of the different agricultural commodities are obtained from Korean Statistical Information Service to create a baseline for future agricultural volcanic loss estimation. Numerically simulated examples of scenario ash fall events at Mt. Baekdu volcano are utilized to illustrate the application of the developed fragility functions. Acknowledgements This research was supported by a grant 'Development of Advanced Volcanic Disaster Response System considering Potential Volcanic Risk around Korea' [MPSS-NH-2015-81] from the Natural Hazard Mitigation Research Group, Ministry of Public Safety and Security of Korea. References Nimlos, T. J. and Hans, Z., The Distribution and Thickness of Volcanic Ash in Montana, Northwest Science, Vol. 56, No. 3, 1982. Wilson, T., Kaye, G., Stewart, C., and Cole, J., Impacts of the 2006 Eruption of Merapi Volcano, Indonesia, on Agriculture and Infrastructure, GNS Science Report, 2007.
Shah, Ravi V.; Murthy, Venkatesh L.; Colangelo, Laura A.; Reis, Jared; Venkatesh, Bharath Ambale; Sharma, Ravi; Abbasi, Siddique A.; Goff, David C.; Carr, J. Jeffrey; Rana, Jamal S.; Terry, James G.; Bouchard, Claude; Sarzynski, Mark A.; Eisman, Aaron; Neilan, Tomas; Das, Saumya; Jerosch-Herold, Michael; Lewis, Cora E.; Carnethon, Mercedes; Lewis, Gregory D.; Lima, Joao A. C.
2017-01-01
Importance Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear. Objective To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD). Design, Setting, and Participants Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up. Main Outcomes and Measures The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated. Results Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = −0.24; 95% CI, −0.45 to −0.03; P = .02) and significantly better lobal longitudinal strain (β = −0.09; 95% CI, −0.14 to −0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found. Conclusions and Relevance Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis. PMID:26618471
Cooper, Leroy L; Palmisano, Joseph N; Benjamin, Emelia J; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Hamburg, Naomi M
2016-12-01
Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied. We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02-13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07-1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71-0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99-1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90-1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69-1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity. Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling. © 2016 American Heart Association, Inc.
Platelet count and total and cause-specific mortality in the Women's Health Initiative.
Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lin, Juan; Lessin, Lawrence; Wassertheil-Smoller, Sylvia; Rohan, Thomas E
2017-04-01
We used data from the Women's Health Initiative to examine the association of platelet count with total mortality, coronary heart disease (CHD) mortality, cancer mortality, and non-CHD/noncancer mortality. Platelet count was measured at baseline in 159,746 postmenopausal women and again in year 3 in 75,339 participants. Participants were followed for a median of 15.9 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline platelet count and of the mean of baseline + year 3 platelet count. Low and high deciles of both baseline and mean platelet count were positively associated with total mortality, CHD mortality, cancer mortality, and non-CHD/noncancer mortality. The association was robust and was not affected by adjustment for a number of potential confounding factors, exclusion of women with comorbidity, or allowance for reverse causality. Low- and high-platelet counts were associated with all four outcomes in never smokers, former smokers, and current smokers. In this large study of postmenopausal women, both low- and high-platelet counts were associated with total and cause-specific mortality. Copyright © 2017 Elsevier Inc. All rights reserved.
Lindman, Brian R; Maniar, Hersh S; Jaber, Wael A; Lerakis, Stamatios; Mack, Michael J; Suri, Rakesh M; Thourani, Vinod H; Babaliaros, Vasilis; Kereiakes, Dean J; Whisenant, Brian; Miller, D Craig; Tuzcu, E Murat; Svensson, Lars G; Xu, Ke; Doshi, Darshan; Leon, Martin B; Zajarias, Alan
2015-04-01
Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313. © 2015 American Heart Association, Inc.
Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale
Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal
2016-01-01
Background In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. Methods The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. Results The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. Conclusions The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification. PMID:27045168
Roychowdhury, D F; Hayden, A; Liepa, A M
2003-02-15
This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.
Ashida, Toyo; Kondo, Naoki; Kondo, Katsunori
2016-08-01
The impact of social participation on older adults' health may differ by individual socioeconomic status (SES). Consequently, we examined SES effect modification on the associations between types of social activity participation and incident functional disability. Cohort data from the 2003 Japan Gerontological Evaluation Study (JAGES) was utilized. This included individuals who were aged 65 or older and functionally independent at baseline. Analysis was carried out on 12,991 respondents after acquisition of information about their long-term care (LTC) status in Japan. Incident functional disability was defined based on medical certification and LTC information was obtained from municipal insurance databases. Cox proportional hazard regression was conducted for analysis. Results indicated that participants in a sport (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.51, 0.85) or hobby group (HR: 0.69; 95% CI: 0.55, 0.87), or who had a group facilitator role (HR: 0.82; 95% CI: 0.66, 1.02) were less likely to be disabled. While men with 13 or more years of education were less likely to become disabled if they held facilitator roles, this association was weak among men with 0-5years of education (HR of interaction term between 0 and 5years of education and facilitator role dummy variable=3.95; 95% CI: 1.30, 12.05). In conclusion, the association between group participation and smaller risk of the functional disability was stronger among highly educated older adults. Intervention programs promoting social participation should consider participants' socioeconomic backgrounds. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
1991-11-01
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Buys, Roselien; Coeckelberghs, Ellen; Cornelissen, Véronique A; Goetschalckx, Kaatje; Vanhees, Luc
2016-09-01
Peak oxygen uptake is an independent predictor of mortality in patients with coronary artery disease (CAD). However, patients with CAD are not always capable of reaching peak effort, and therefore submaximal gas exchange variables such as the oxygen uptake efficiency slope (OUES) have been introduced. Baseline exercise capacity as expressed by OUES provides prognostic information and this parameter responds to training. Therefore, we aimed to assess the prognostic value of post-training OUES in patients with CAD. We included 960 patients with CAD (age 60.6 ± 9.5 years; 853 males) who completed a cardiac rehabilitation program between 2000 and 2011. The OUES was calculated before and after cardiac rehabilitation and information on mortality was obtained. The relationships of post-training OUES with all-cause and cardiovascular (CV) mortality was assessed by Cox proportional hazards regression analyses. Receiver operator characteristic curve analysis was performed in order to obtain the optimal cut-off value. During 7.37 ± 3.20 years of follow-up (range: 0.45-13.75 years), 108 patients died, among whom 47 died due to CV reasons. The post-training OUES was related to all-cause (hazard ratio: 0.50, p < 0.001) and CV (hazard ratio: 0.40, p < 0.001) mortality. When significant covariates, including baseline OUES, were entered into the Cox regression analysis, post-training OUES remained related to all-cause and CV mortality (hazard ratio: 0.40, p < 0.01 and 0.26, p < 0.01, respectively). In addition, the change in OUES due to exercise training was positively related to mortality (hazard ratio: 0.49, p < 0.01). Post-training OUES has stronger prognostic value compared to baseline OUES. The lack of improvement in exercise capacity expressed by OUES after an exercise training program relates to a worse prognosis and can help distinguish patients with favorable and unfavorable prognoses. © The European Society of Cardiology 2016.
Association Between Cortisol to DHEA-s Ratio and Sickness Absence in Japanese Male Workers.
Hirokawa, Kumi; Fujii, Yasuhito; Taniguchi, Toshiyo; Takaki, Jiro; Tsutsumi, Akizumi
2018-06-01
This study aimed to investigate the association between serum levels of cortisol and dehydroepiandrosterone sulfate (DHEA-s) and sickness absence over 2 years in Japanese male workers. A baseline survey including questions about health behavior, along with blood sampling for cortisol and DHEA-s, was conducted in 2009. In total, 429 men (mean ± SD age, 52.9 ± 8.6 years) from whom blood samples were collected at baseline were followed until December 31, 2011. The hazard ratios (HR) and 95% confidence intervals (CI) for sickness absence were calculated using a Cox proportional hazard model, adjusted for potential confounders. Among 35 workers who took sickness absences, 31 had physical illness. A high cortisol to DHEA-s ratio increased the risk of sickness absence (crude HR = 2.68, 95% CI 1.12-6.41; adjusted HR = 3.33, 95% CI 1.35-8.20). The cortisol to DHEA-s ratio was linearly associated with an increased risk of sickness absence (p for trend < .050). Single effects of cortisol and DHEA-s levels were not associated with sickness absences. This trend did not change when limited to absences resulting from physical illness. Hormonal conditions related to the hypothalamus-pituitary-adrenocortical axis and adrenal function should be considered when predicting sickness absence. The cortisol to DHEA-s ratio may be more informative than single effects of cortisol and DHEA-s levels.
Turner, Aaron P; Hartoonian, Narineh; Maynard, Charles; Leipertz, Steven L; Haselkorn, Jodie K
2015-03-01
To examine 2 modifiable health behaviors-smoking and physical activity-and their relationship to mortality among individuals with multiple sclerosis (MS). Secondary analysis of Large Health Survey. Data were obtained from a linkage of the Veterans Affairs (VA) MS National Data Repository, containing information on service provision to all individuals with MS receiving health services within the U.S. Department of Veterans Affairs; the VA 1999 Large Health Survey, containing information on smoking and physical activity; and the VA Vital Status File. All-cause mortality was examined for the 15-year period from 1999 through 2013. Participants (N=2994) with MS who completed the Large Health Survey containing information on smoking and physical activity. Not applicable. Survival. There were 1500 deaths (50.1%) during the study period. Cox proportional hazard analyses were conducted to examine the association between smoking and physical activity and 15-year mortality. After adjusting for demographic factors, physical functioning, mental health, and comorbid medical conditions, baseline smoking was associated with greater mortality (hazard ratio [HR]=1.38; 95% confidence interval [CI], 1.184-1.60). Higher levels of baseline physical activity were associated with lower mortality (activity 1-2 times/wk: HR=.64; 95% CI, .518-.798; activity ≥3 times/wk: HR=.53; 95% CI, .388-.715). Results suggest that modifiable health behaviors represent a promising opportunity for intervention to improve the lives of individuals with MS. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Boudreau, Robert M; Hanlon, Joseph T; Roumani, Yazan F; Studenski, Stephanie A; Ruby, Christine M; Wright, Rollin M; Hilmer, Sarah N; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Newman, Anne B
2009-10-01
To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation. This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications. Each year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk were seen in analyses examining dose- and duration-response relationships. CNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. 2009 John Wiley & Sons, Ltd.
Cirillo, Massimo; Bilancio, Giancarlo; Lombardi, Cinzia; Cavallo, Pierpaolo; Terradura Vagnarelli, Oscar; Zanchetti, Alberto; Laurenzi, Martino
2018-02-01
Research data are limited on indices of osmotic equilibrium and of kidney concentrating activity (KCA). This study investigated correlates and prognostic power of these indices in a sample of the general population. Urine osmolality (U-osm), plasma osmolality (P-osm), plasma creatinine and other variables were measured by the Gubbio Study for the 1988-92 exam (baseline). Plasma creatinine and other variables were re-measured in the 2001-07 exam (follow-up). KCA was assessed as the U-osm/P-osm ratio and kidney function as estimated glomerular filtration rate (eGFR). Baseline data were complete in 4220 adults, of whom 852 died before follow-up and 2795 participated in the follow-up. At baseline, the following independent cross-sectional associations were identified: female sex and higher urine flow with lower values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); obesity with higher values of U-osm, P-osm and U-osm/P-osm ratio (P < 0.01); older age and lower eGFR with lower U-osm, lower U-osm/P-osm ratio and higher P-osm (P < 0.05); hypertension and smoking with lower U-osm and lower U-osm/P-osm ratio (P < 0.05) but not with P-osm. From baseline to follow-up, the annualized rate was 1.26% for mortality and -0.74 ± 0.76 mL/min × 1.73 m2 for eGFR change. Mortality was independently predicted by baseline U-osm and baseline U-osm/P-osm ratio (hazard ratio for one higher standard deviation was ≤0.91, 95% confidence interval was ≤0.97, P < 0.01), but not by baseline P-osm. The eGFR change was not independently predicted by baseline values of U-osm, P-osm and U-osm/P-osm ratio (P ≥ 0.4). Sex, age, obesity, eGFR, urine flow, hypertension and smoking independently associated with U-osm and KCA. U-osm and KCA independently predicted mortality, but not kidney function change over time. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
McDonald, Catherine C; Kandadai, Venk; Loeb, Helen; Seacrist, Thomas; Lee, Yi-Ching; Bonfiglio, Dana; Fisher, Donald L; Winston, Flaura K
Collisions at left turn intersections are among the most prevalent types of teen driver serious crashes, with inadequate surveillance as a key factor. Risk awareness perception training (RAPT) has shown effectiveness in improving hazard anticipation for latent hazards. The goal of this study was to determine if RAPT version 3 (RAPT-3) improved intersection turning behaviors among novice teen drivers when the hazards were not latent and frequent glancing to multiple locations at the intersection was needed. Teens aged 16-18 with ≤180 days of licensure were randomly assigned to: 1) an intervention group (n=18) that received RAPT-3 (Trained); or 2) a control group (n=19) that received no training (Untrained). Both groups completed RAPT-3 Baseline Assessment and the Trained group completed RAPT-3 Training and RAPT-3 Post Assessment. Training effects were evaluated on a driving simulator. Simulator ( gap selection errors and collisions ) and eye tracker ( traffic check errors) metrics from six left-turn stop sign controlled intersections in the Simulated Driving Assessment (SDA) were analyzed. The Trained group scored significantly higher in RAPT-3 Post Assessment than RAPT-3 Baseline Assessment (p< 0.0001). There were no significant differences in either traffic check and gap selection errors or collisions among Trained and Untrained teens in the SDA. Though Trained teens learned about hazard anticipation related to latent hazards, learning did not translate to performance differences in left-turn stop sign controlled intersections where the hazards were not latent. Our findings point to further research to better understand the challenges teens have with left turn intersections.
Brown, Allen W; Leibson, Cynthia L; Mandrekar, Jay; Ransom, Jeanine E; Malec, James F
2014-01-01
To examine the contribution of co-occurring nonhead injuries to hazard of death after traumatic brain injury (TBI). A random sample of Olmsted County, Minnesota, residents with confirmed TBI from 1987 through 1999 was identified. Each case was assigned an age- and sex-matched, non-TBI "regular control" from the population. For "special cases" with accompanying nonhead injuries, 2 matched "special controls" with nonhead injuries of similar severity were assigned. Vital status was followed from baseline (ie, injury date for cases, comparable dates for controls) through 2008. Cases were compared first with regular controls and second with regular or special controls, depending on case type. In total, 1257 cases were identified (including 221 special cases). For both cases versus regular controls and cases versus regular or special controls, the hazard ratio was increased from baseline to 6 months (10.82 [2.86-40.89] and 7.13 [3.10-16.39], respectively) and from baseline through study end (2.92 [1.74-4.91] and 1.48 [1.09-2.02], respectively). Among 6-month survivors, the hazard ratio was increased for cases versus regular controls (1.43 [1.06-2.15]) but not for cases versus regular or special controls (1.05 [0.80-1.38]). Among 6-month survivors, accounting for nonhead injuries resulted in a nonsignificant effect of TBI on long-term mortality.
Memory Hazard Functions: A Vehicle for Theory Development and Test
ERIC Educational Resources Information Center
Chechile, Richard A.
2006-01-01
A framework is developed to rigorously test an entire class of memory retention functions by examining hazard properties. Evidence is provided that the memory hazard function is not monotonically decreasing. Yet most of the proposals for retention functions, which have emerged from the psychological literature, imply that memory hazard is…
Jahangiri, Younes; Kerrigan, Timothy; Li, Lei; Prosser, Dominik; Brar, Anantnoor; Righetti, Johnathan; Schenning, Ryan C; Kaufman, John A; Farsad, Khashayar
2017-12-01
To identify risk factors of stent graft thrombosis after transjugular intrahepatic portosystemic shunt (TIPS) creation. Patients who underwent TIPS creation between June 2003 and January 2016 and with follow-up assessing stent graft patency were included (n=174). Baseline comorbidities, liver function, procedural details and follow-up liver function tests were analyzed in association with hazards of thrombosis on follow-up. Competing risk cox regression models were used considering liver transplant after TIPS creation as the competing risk variable. One-, 2- and 5-year primary patency rates were 94.1%, 91.7% and 78.2%, respectively. Patient age [sub-hazard ratio (sHR): 1.13; P=0.001], body mass index (BMI) <30 (sHR: 33.08; P=0.008) and a higher post-TIPS portosystemic pressure gradient (sHR: 1.14; P=0.023) were significantly associated with TIPS thrombosis in multivariate analysis. A higher rate of TIPS thrombosis was observed in those for whom the procedure was clinically unsuccessful (P=0.014). A significant increase in incidence of thrombosis was noted with increasing tertiles of post-TIPS portosystemic gradients (P value for trend=0.017). Older age, lower BMI and higher post-TIPS portosystemic gradients were associated with higher hazards of shunt thrombosis after TIPS creation using stent grafts. Higher rates of shunt thrombosis were seen in patients for whom TIPS creation was clinically unsuccessful. The association between TIPS thrombosis and higher post-TIPS portosystemic gradients may indicate impaired flow through the shunt, a finding which may be technical or anatomic in nature and should be assessed before procedure completion.
2015-02-11
A similar risk-based approach may be appropriate for deploying military personnel. e) If DoD were to consider implementing a large- scale pre...quality of existing spirometry programs prior to considering a larger scale pre-deployment effort. Identifying an accelerated decrease in spirometry...baseline spirometry on a wider scale . e) Conduct pre-deployment baseline spirometry if there is a significant risk of exposure to a pulmonary hazard based
Coleman, Craig I; Bunz, Thomas J; Turpie, Alexander G G
2017-10-05
The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.
Hung, Kristin J; Awtrey, Christopher S; Tsai, Alexander C
2014-04-01
To estimate the association between urinary incontinence (UI) and probable depression, work disability, and workforce exit. The analytic sample consisted of 4,511 women enrolled in the population-based Health and Retirement Study cohort. The analysis baseline was 1996, the year that questions about UI were added to the survey instrument, and at which time study participants were 54-65 years of age. Women were followed-up with biennial interviews until 2010-2011. Outcomes of interest were onset of probable depression, work disability, and workforce exit. Urinary incontinence was specified in different ways based on questions about experience and frequency of urine loss. We fit Cox proportional hazards regression models to the data, adjusting the estimates for baseline sociodemographic and health status variables previously found to confound the association between UI and the outcomes of interest. At baseline, 727 participants (survey-weighted prevalence, 16.6%; 95% confidence interval [CI] 15.4-18.0) reported any UI, of which 212 (survey-weighted prevalence, 29.2%; 95% CI 25.4-33.3) reported urine loss on more than 15 days in the past month; and 1,052 participants were categorized as having probable depression (survey-weighted prevalence, 21.6%; 95% CI 19.8-23.6). Urinary incontinence was associated with increased risks for probable depression (adjusted hazard ratio, 1.43; 95% CI 1.27-1.62) and work disability (adjusted hazard ratio, 1.21; 95% CI 1.01-1.45), but not workforce exit (adjusted hazard ratio, 1.06; 95% CI 0.93-1.21). In a population-based cohort of women between ages 54 and 65 years, UI was associated with increased risks for probable depression and work disability. Improved diagnosis and management of UI may yield significant economic and psychosocial benefits.
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA, 1980) (CERCLA or Superfund) was enacted to provide a program for identifying and responding to releases of hazardous substances into the environment. The Superfund Amendments and Reauthorization Act (SARA, 1986) was enacted to strengthen CERCLA by requiring that site clean-ups be permanent, and that they use treatments that significantly reduce the volume, toxicity, or mobility of hazardous pollutants. The National Oil and Hazardous Substances Pollution Contingency Plan (NCP) (USEPA, 1985; USEPA, 1990) implements the CERCLA statute, presenting a process for (1) identifying and prioritizing sites requiring remediation and (2) assessing themore » extent of remedial action required at each site. The process includes performing two studies: a Remedial Investigation (RI) to evaluate the nature, extent, and expected consequences of site contamination, and a Feasibility Study (FS) to select an appropriate remedial alternative adequate to reduce such risks to acceptable levels. An integral part of the RI is the evaluation of human health risks posed by hazardous substance releases. This risk evaluation serves a number of purposes within the overall context of the RI/FS process, the most essential of which is to provide an understanding of ``baseline`` risks posed by a given site. Baseline risks are those risks that would exist if no remediation or institutional controls are applied at a site. This document was written to (1) guide risk assessors through the process of interpreting EPA BRA policy and (2) help risk assessors to discuss EPA policy with regulators, decision makers, and stakeholders as it relates to conditions at a particular DOE site.« less
Sun, Yanqing; Qi, Li; Yang, Guangren; Gilbert, Peter B
2018-05-01
This article develops hypothesis testing procedures for the stratified mark-specific proportional hazards model with missing covariates where the baseline functions may vary with strata. The mark-specific proportional hazards model has been studied to evaluate mark-specific relative risks where the mark is the genetic distance of an infecting HIV sequence to an HIV sequence represented inside the vaccine. This research is motivated by analyzing the RV144 phase 3 HIV vaccine efficacy trial, to understand associations of immune response biomarkers on the mark-specific hazard of HIV infection, where the biomarkers are sampled via a two-phase sampling nested case-control design. We test whether the mark-specific relative risks are unity and how they change with the mark. The developed procedures enable assessment of whether risk of HIV infection with HIV variants close or far from the vaccine sequence are modified by immune responses induced by the HIV vaccine; this question is interesting because vaccine protection occurs through immune responses directed at specific HIV sequences. The test statistics are constructed based on augmented inverse probability weighted complete-case estimators. The asymptotic properties and finite-sample performances of the testing procedures are investigated, demonstrating double-robustness and effectiveness of the predictive auxiliaries to recover efficiency. The finite-sample performance of the proposed tests are examined through a comprehensive simulation study. The methods are applied to the RV144 trial. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A
2011-08-01
The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.
Kamel, Hooman; Soliman, Elsayed Z; Heckbert, Susan R; Kronmal, Richard A; Longstreth, W T; Nazarian, Saman; Okin, Peter M
2014-09-01
Emerging data suggest that left atrial disease may cause ischemic stroke in the absence of atrial fibrillation or flutter (AF). If true, this condition may provide a cause for many strokes currently classified as cryptogenic. Among 6741 participants in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cerebrovascular or cardiovascular disease (including AF) at baseline, we examined the association between markers of left atrial abnormality on a standard 12-lead ECG-specifically P-wave area, duration, and terminal force in lead V1-and the subsequent risk of ischemic stroke while accounting for incident AF. During a median follow-up of 8.5 years, 121 participants (1.8%) had a stroke and 541 participants (8.0%) were diagnosed with AF. In Cox proportional hazards models adjusting for potential baseline confounders, P-wave terminal force in lead V1 was more strongly associated with incident stroke (hazard ratio per 1 SD increase, 1.21; 95% confidence interval, 1.02-1.44) than with incident AF (hazard ratio per 1 SD, 1.11; 95% confidence interval, 1.03-1.21). The association between P-wave terminal force in lead V1 and stroke was robust in numerous sensitivity analyses accounting for AF, including analyses that excluded those with any incident AF or modeled any incident AF as having been present from baseline. We found an association between baseline P-wave morphology and incident stroke even after accounting for AF. This association may reflect an atrial cardiopathy that leads to stroke in the absence of AF. © 2014 American Heart Association, Inc.
Wang, G; Xu, W G; Li, F; Su, K; Li, N; Lü, Z Y; Feng, X S; Wei, L P; Chen, H D; Chen, Y H; Guo, L W; Cui, H; Yang, W J; Li, Z F; Ren, J S; Wu, S L; Shi, J F; Dai, M; He, J
2017-10-31
Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios ( HR ) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P =0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer ( HR =1.38, 95% CI: 1.05-1.81, P =0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.
Exposure to smoking depictions in movies: its association with established adolescent smoking.
Sargent, James D; Stoolmiller, Mike; Worth, Keilah A; Dal Cin, Sonya; Wills, Thomas A; Gibbons, Frederick X; Gerrard, Meg; Tanski, Susanne
2007-09-01
To assess the association between exposure to movie smoking and established adolescent smoking. Longitudinal survey of a representative US adolescent sample. Adolescents were surveyed by telephone in their homes. Sixty-five hundred twenty-two US adolescents aged 10 to 14 years at baseline, resurveyed at 8 months (8M) (n = 5503), 16 months (16M) (n = 5019), and 24 months (24M) (n = 4575). Main Exposure Exposure to smoking in 532 box-office hits released in the 5 years prior to the baseline survey. Outcome Measure Established smoking (having smoked more than 100 cigarettes during lifetime). Of 108 incident established smokers with data at the 24M survey, 85% were current (30-day smokers) and 83% endorsed at least 1 addiction symptom. Established smoking incidence was 7.4, 15.8, and 19.7 per 1000 person-years of observation for the baseline-to-8M, 8M-to-16M, and 16M-to-24M observation periods, respectively. In a multivariate survival model, risk of established smoking was predicted by baseline exposure to smoking in movies with an adjusted overall hazard ratio of 2.04 (95% confidence interval, 1.01-4.12) for teens in the 95th percentile of movie-smoking exposure compared with the 5th percentile. This effect was independent of age; parent, sibling, or friend smoking; and sensation seeking. Teens low on sensation seeking were more responsive to the movie-smoking effect (hazard ratio, 12.7; 95% confidence interval, 2.0-80.6) compared with teens who were high on sensation seeking (hazard ratio, 1.01; 95% confidence interval, 0.4-2.6). In this national US adolescent sample, exposure to smoking in movies predicted risk of becoming an established smoker, an outcome linked with adult dependent smoking and its associated morbidity and mortality.
Mentz, Robert J; Greiner, Melissa A; DeVore, Adam D; Dunlay, Shannon M; Choudhary, Gaurav; Ahmad, Tariq; Khazanie, Prateeti; Randolph, Tiffany C; Griswold, Michael E; Eapen, Zubin J; O'Brien, Emily C; Thomas, Kevin L; Curtis, Lesley H; Hernandez, Adrian F
2015-03-01
QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities. © 2015 American Heart Association, Inc.
'I didn't see that coming': simulated visual fields and driving hazard perception test performance.
Glen, Fiona C; Smith, Nicholas D; Jones, Lee; Crabb, David P
2016-09-01
Evidence is limited regarding specific types of visual field loss associated with unsafe driving. We use novel gaze-contingent software to examine the effect of simulated visual field loss on computer-based driving hazard detection with the specific aim of testing the impact of scotomata located to the right and left of fixation. The 'hazard perception test' is a component of the UK driving licence examination, which measures speed of detecting 15 different hazards in a series of real-life driving films. We have developed a novel eye-tracking and computer set up capable of generating a realistic gaze-contingent scotoma simulation (GazeSS) overlaid on film content. Thirty drivers with healthy vision completed three versions of the hazard perception test in a repeated measures experiment. In two versions, GazeSS simulated a scotoma in the binocular field of view to the left or right of fixation. A third version was unmodified to establish baseline performance. Participants' mean baseline hazard perception test score was 51 ± 7 (out of 75). This reduced to 46 ± 9 and 46 ± 11 when completing the task with a binocular visual field defect located to the left and right of fixation, respectively. While the main effect of simulated visual field loss on performance was statistically significant (p = 0.007), there were no average differences in the experimental conditions where a scotoma was located in the binocular visual field to the right or left of fixation. Simulated visual field loss impairs driving hazard detection on a computer-based test. There was no statistically significant difference in average performance when the simulated scotoma was located to the right or left of fixation of the binocular visual field, but certain types of hazard caused more difficulties than others. © 2016 Optometry Australia.
Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers.
Fesseha, Betiel K; Abularrage, Christopher J; Hines, Kathryn F; Sherman, Ronald; Frost, Priscilla; Langan, Susan; Canner, Joseph; Likes, Kendall C; Hosseini, Sayed M; Jack, Gwendolyne; Hicks, Caitlin W; Yalamanchi, Swaytha; Mathioudakis, Nestoras
2018-04-16
This study evaluated the association between hemoglobin A 1c (A1C) and wound outcomes in patients with diabetic foot ulcers (DFUs). We conducted a retrospective analysis of an ongoing prospective, clinic-based study of patients with DFUs treated at an academic institution during a 4.7-year period. Data from 270 participants and 584 wounds were included in the analysis. Cox proportional hazards regression was used to assess the incidence of wound healing at any follow-up time in relation to categories of baseline A1C and the incidence of long-term (≥90 days) wound healing in relation to tertiles of nadir A1C change and mean A1C change from baseline, adjusted for potential confounders. Baseline A1C was not associated with wound healing in univariate or fully adjusted models. Compared with a nadir A1C change from baseline of -0.29 to 0.0 (tertile 2), a nadir A1C change of 0.09 to 2.4 (tertile 3) was positively associated with long-term wound healing in the subset of participants with baseline A1C <7.5% (hazard ratio [HR], 2.07; 95% CI, 1.08-4.00), but no association with wound healing was seen with the mean A1C change from baseline in this group. Neither nadir A1C change nor mean A1C change were associated with long-term wound healing in participants with baseline A1C ≥7.5%. There does not appear to be a clinically meaningful association between baseline or prospective A1C and wound healing in patients with DFUs. The paradoxical finding of accelerated wound healing and increase in A1C in participants with better baseline glycemic control requires confirmation in further studies. © 2018 by the American Diabetes Association.
Kim, Gyuri; Lee, Seung-Eun; Jun, Ji Eun; Lee, You-Bin; Ahn, Jiyeon; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Jee, Jae Hwan; Lee, Moon-Kyu; Kim, Jae Hyeon
2018-02-05
Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes < 0% over a year, multivariate-AHRs for metabolic syndrome development were 0.87 (95% CI 0.78-0.97) for 0-1% changes and 0.67 (0.56-0.79) for > 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.
Sumner, Jennifer A; Khodneva, Yulia; Muntner, Paul; Redmond, Nicole; Lewis, Marquita W; Davidson, Karina W; Edmondson, Donald; Richman, Joshua; Safford, Monika M
2016-10-10
Psychosocial risk for cardiovascular disease (CVD) may be especially deleterious in persons with low socioeconomic status. Most work has focused on psychosocial factors individually, but emerging research suggests that the confluence of psychosocial risk may be particularly harmful. Using data from the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, we examined associations among depressive symptoms and stress, alone and in combination, and incident CVD and all-cause mortality as a function of socioeconomic status. At baseline, 22 658 participants without a history of CVD (58.8% female, 41.7% black, mean age 63.9±9.3 years) reported on depressive symptoms, stress, annual household income, and education. Participants were classified into 1 of 3 psychosocial risk groups at baseline: (1) neither depressive symptoms nor stress, (2) either depressive symptoms or stress, or (3) both depressive symptoms and stress. Cox proportional hazards models were used to predict physician-adjudicated incident total CVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and all-cause mortality over a median of 7.0 years (interquartile range 5.4-8.3 years) of follow-up. In fully adjusted models, participants with both depressive symptoms and stress had the greatest elevation in risk of developing total CVD (hazard ratio 1.48, 95% CI 1.21-1.81) and all-cause mortality (hazard ratio 1.33, 95% CI 1.13-1.56) but only for those with low income (<$35 000) and not high (≥$35 000) income. This pattern of results was not observed in models stratified by education. Findings suggest that screening for a combination of elevated depressive symptoms and stress in low-income persons may help identify those at increased risk of incident CVD and mortality. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Exercise Is Associated with Lower Long-Term Risk of Olfactory Impairment in Older Adults
Schubert, Carla R.; Cruickshanks, Karen J.; Nondahl, David M.; Klein, Barbara EK; Klein, Ronald; Fischer, Mary E.
2013-01-01
Importance The prevalence of olfactory impairment is high in older adults and this decline in olfactory ability may pose health and safety risks, affect nutrition and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objectives To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n=1611) were ages 53-97 years at baseline and were followed for up to ten years (1998-2010). Interventions None Main Outcome and Measures Olfaction was measured with the San Diego Odor Identification Test at three examinations (1998-2000, 2003-2005, 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment five (2003-2005) or ten (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% confidence interval =25.3, 29.9) and rates varied by age and sex; those who were older (Hazard Ratio =1.88, 95% Confidence Interval=1.74, 2.03, for every 5 years) or male (Hazard Ratio=1.27, 95% Confidence Interval=1.00, 1.61) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age and sex adjusted Hazard Ratio= 0.76, 95% CI= 0.60, 0.97). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment (p for trend = 0.02). Conclusion and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age. PMID:24135745
Takatori, Kosuke; Aihara, Maki; Sugita-Konishi, Yoshiko
2006-01-01
In recent years, various food-related accidents and health scares have dissipated trust in the food industry. Health hazards resulting from food contaminated with fungi is increasing. Food contamination by fungi causes many problems, especially in Japan, which relies on foreign countries for about 60% of its food: the contamination of imported food by fungi and mycotoxins constitutes a serious problem. As the quantity of imported food increases and changes in food distribution have occurred, so too has the number and type of fungi causing food-related damages; osmophilic and thermotolerant fungi, in addition to the mainstream fungi of genera Cladosporium, Pecinillium, and Aspergillus, have become a problem. Although European countries and the U.S. have recently conducted risk assessments for mycotoxins, Japan has not attained an international level in the determination of baseline values. However, in addition to risk management for Aflatoxin M1, Ochratoxin, T-2 toxin/HT-2 toxin, and Fumonisin, determination of baseline values for mycotoxins is beginning in Japan. In this review, we summarize hazardous food-borne fungi, and present and future approaches to the mycotoxin regulations in Japan.
Schubert, Carla R; Paulsen, Adam J; Nondahl, David M; Dalton, Dayna S; Fischer, Mary E; Klein, Barbara E K; Klein, Ronald; Tweed, Ted S; Cruickshanks, Karen J
2018-06-01
Hearing impairment (HI) is one of the most common conditions affecting older adults. Identification of factors associated with the development of HI may lead to ways to reduce the incidence of this condition. To investigate the association between cystatin C, both as an independent biomarker and as a marker of kidney function, and the 20-year incidence of HI. Data were obtained from the Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study in Beaver Dam, Wisconsin. Baseline examinations began in 1993 and continued through 1995, and participants were examined approximately every 5 years, with the most recent examination phase completed in 2015. The EHLS participants with serum cystatin C concentration data and without HI at the baseline examination were included in this study. Participants without HI were followed up for incident HI (pure-tone average of hearing thresholds at 0.5, 1, 2, and 4 kHz >25 dB hearing level in either ear) for 20 years. Cystatin C was analyzed as a biomarker (concentration) and used to determine estimated glomerular filtration rate (eGFRCysC). Discrete-time Cox proportional hazards regression models were used to analyze the association between cystatin C concentration and eGFRCysC and the 20-year cumulative incidence of HI. There were 863 participants aged 48 to 86 years with cystatin C data and without HI at baseline. Of these, 599 (69.4%) were women. In models adjusted for age and sex, cystatin C was associated with an increased risk of developing HI (hazard ratio [HR], 1.20; 95% CI, 1.07-1.34 per 0.2-mg/L increase in cystatin C concentration), but the estimate was attenuated after further adjusting for educational level, current smoking, waist circumference, and glycated hemoglobin (HR, 1.11; 95% CI, 0.98-1.27 per 0.2-mg/L increase in cystatin C concentration). Low eGFRCysC was significantly associated with the 20-year cumulative incidence of HI in both the age- and sex-adjusted model (HR, 1.70; 95% CI, 1.16-2.48; <60 vs ≥60 mL/min/1.73 m2) and the multivariable-adjusted model (HR, 1.50; 95% CI, 1.02-2.22; <60 vs ≥60 mL/min/1.73 m2). Reduced kidney function as estimated using cystatin C, but not cystatin C alone, was associated with the 20-year cumulative incidence of HI, suggesting that some age-related HI may occur in conjunction with or as the result of reduced kidney function.
DOE Office of Scientific and Technical Information (OSTI.GOV)
David A. King
2012-11-29
This environmental baseline survey (EBS) report documents the baseline environmental conditions of five land parcels located near the U.S. Department of Energy’s (DOE’s) East Tennessee Technology Park (ETTP), including West Black Oak Ridge, East Black Oak Ridge, McKinney Ridge, West Pine Ridge, and Parcel 21d. The goal is to obtain all media no-further-investigation (NFI) determinations for the subject parcels considering existing soils. To augment the existing soils-only NFI determinations, samples of groundwater, surface water, soil, and sediment were collected to support all media NFI decisions. The only updates presented here are those that were made after the original issuance ofmore » the NFI documents. In the subject parcel where the soils NFI determination was not completed for approval (Parcel 21d), the full process has been performed to address the soils as well. Preparation of this report included the detailed search of federal government records, title documents, aerial photos that may reflect prior uses, and visual inspections of the property and adjacent properties. Interviews with current employees involved in, or familiar with, operations on the real property were also conducted to identify any areas on the property where hazardous substances and petroleum products, or their derivatives, and acutely hazardous wastes may have been released or disposed. In addition, a search was made of reasonably obtainable federal, state, and local government records of each adjacent facility where there has been a release of any hazardous substance or any petroleum product or their derivatives, including aviation fuel and motor oil, and which is likely to cause or contribute to a release of any hazardous substance or any petroleum product or its derivatives, including aviation fuel or motor oil, on the real property. A radiological survey and soil/sediment sampling was conducted to assess baseline conditions of Parcel 21d that were not addressed by the soils-only NFI reports. Groundwater sampling was also conducted to support a Parcel 21d decision.« less
Process Waste Assessment for the Diana Laser Laboratory
DOE Office of Scientific and Technical Information (OSTI.GOV)
Phillips, N.M.
1993-12-01
This Process Waste Assessment was conducted to evaluate the Diana Laser Laboratory, located in the Combustion Research Facility. It documents the hazardous chemical waste streams generated by the laser process and establishes a baseline for future waste minimization efforts. This Process Waste Assessment will be reevaluated in approximately 18 to 24 months, after enough time has passed to implement recommendations and to compare results with the baseline established in this assessment.
White Blood Cell Count and Total and Cause-Specific Mortality in the Women's Health Initiative.
Kabat, Geoffrey C; Kim, Mimi Y; Manson, JoAnn E; Lessin, Lawrence; Lin, Juan; Wassertheil-Smoller, Sylvia; Rohan, Thomas E
2017-07-01
White blood cell (WBC) count appears to predict total mortality and coronary heart disease (CHD) mortality, but it is unclear to what extent the association reflects confounding by smoking, underlying illness, or comorbid conditions. We used data from the Women's Health Initiative to examine the associations of WBC count with total mortality, CHD mortality, and cancer mortality. WBC count was measured at baseline in 160,117 postmenopausal women and again in year 3 in 74,375 participants. Participants were followed for a mean of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline WBC count and of the mean of baseline + year 3 WBC count. High deciles of both baseline and mean WBC count were positively associated with total mortality and CHD mortality, whereas the association with cancer mortality was weaker. The association of WBC count with mortality was independent of smoking and did not appear to be influenced by previous disease history. The potential clinical utility of this common laboratory test in predicting mortality risk warrants further study. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E
2016-09-01
The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.
Barr, Elizabeth L M; Barzi, Federica; Hughes, Jaquelyne T; Jerums, George; Hoy, Wendy E; O'Dea, Kerin; Jones, Graham R D; Lawton, Paul D; Brown, Alex D H; Thomas, Mark; Ekinci, Elif I; Sinha, Ashim; Cass, Alan; MacIsaac, Richard J; Maple-Brown, Louise J
2018-04-01
To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA 1c , C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR <60 mL/min/1.73 m 2 , progression to renal replacement therapy, or renal death) for increasing sTNFR1. Over a median of 3 years, participants with diabetes ( n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (-4.22 mL/min/1.73 m 2 /year [95% CI -7.06 to -1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome ( n = 32) was 3.8 (1.1-12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes ( n = 259). sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression. © 2018 by the American Diabetes Association.
2014-01-01
Background Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. Methods The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). Results Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. Conclusion Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis. PMID:24410736
Kabagambe, Edmond K; Ezeamama, Amara E; Guwatudde, David; Campos, Hannia; Fawzi, Wafaie
2016-12-15
Fatty acids, including n-6 series, modulate immune function, but their effect on CD4 cell counts, death, or hospitalization in HIV-infected patients on antiretroviral therapy is unknown. In a randomized trial for effects of multivitamins in HIV-infected patients in Uganda, we used gas chromatography to measure plasma n-6 fatty acids at baseline; determined CD4 counts at baseline, 3, 6, 12, and 18 months; and recorded hospitalization or death events. The associations of fatty acids with CD4 counts and events were analyzed using repeated-measures analysis of variance and Cox regression, respectively. Among 297 patients with fatty acids measurements, 16 patients died and 69 were hospitalized within 18 months. Except for linoleic acid, n-6 fatty acids levels were positively associated with CD4 counts at baseline but not during follow-up. In models that included all 5 major n-6 fatty acids, age; sex; body mass index; anemia status; use of antiretroviral therapy, multivitamin supplements, and alcohol; and the risk of death or hospitalization decreased significantly with an increase in linoleic acid and gamma-linolenic acid levels, whereas associations for dihomo-gamma-linolenic acid, arachidonic acid, and aolrenic acid were null. The hazard ratios (95% confidence intervals) per 1 SD increase in linoleic acid and gamma-linolenic acid were 0.73 (0.56-0.94) and 0.51 (0.36-0.72), respectively. Gamma-linolenic acid remained significant (hazard ratio = 0.51; 95% confidence interval: 0.35 to 0.68) after further adjustment for other plasma fatty acids. Lower levels of gamma-linolenic acid are associated with lower CD4 counts and an increased risk of death or hospitalization. These results suggest a potential for using n-6 fatty acids to improve outcomes from antiretroviral therapy.
Rate of Change in Renal Function and Mortality in Elderly Treated Hypertensive Patients
Langham, Robyn G.; Ademi, Zanfina; Owen, Alice; Krum, Henry; Wing, Lindon M.H.; Nelson, Mark R.; Reid, Christopher M.
2015-01-01
Background and objectives Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate’s association with all-cause and cardiovascular mortality. Design, setting, participants, & measurements Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995–1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5). Results A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR. Conclusions In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality. PMID:25901093
Rate of change in renal function and mortality in elderly treated hypertensive patients.
Chowdhury, Enayet K; Langham, Robyn G; Ademi, Zanfina; Owen, Alice; Krum, Henry; Wing, Lindon M H; Nelson, Mark R; Reid, Christopher M
2015-07-07
Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate's association with all-cause and cardiovascular mortality. Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged ≥65 years were enrolled during 1995-1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5). A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure <140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR. In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality. Copyright © 2015 by the American Society of Nephrology.
Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.
Baena-Díez, Jose Miguel; Peñafiel, Judit; Subirana, Isaac; Ramos, Rafel; Elosua, Roberto; Marín-Ibañez, Alejandro; Guembe, María Jesús; Rigo, Fernando; Tormo-Díaz, María José; Moreno-Iribas, Conchi; Cabré, Joan Josep; Segura, Antonio; García-Lareo, Manel; Gómez de la Cámara, Agustín; Lapetra, José; Quesada, Miquel; Marrugat, Jaume; Medrano, Maria José; Berjón, Jesús; Frontera, Guiem; Gavrila, Diana; Barricarte, Aurelio; Basora, Josep; García, Jose María; Pavone, Natalia C; Lora-Pablos, David; Mayoral, Eduardo; Franch, Josep; Mata, Manel; Castell, Conxa; Frances, Albert; Grau, María
2016-11-01
Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes. © 2016 by the American Diabetes Association.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1989-01-01
This volume is one in a series of manuals prepared for EPA to assist its Remedial Project Managers in the assessment of the air contaminant pathway and developing input data for risk assessment. The manual provides guidance on developing baseline-emission estimates from hazardous waste sites. Baseline-emission estimates (BEEs) are defined as emission rates estimated for a site in its undisturbed state. Specifically, the manual is intended to: Present a protocol for selecting the appropriate level of effort to characterize baseline air emissions; Assist site managers in designing an approach for BEEs; Describe useful technologies for developing site-specific baseline emission estimatesmore » (BEEs); Help site managers select the appropriate technologies for generating site-specific BEEs.« less
King, Cheryl A.; Kerr, David C. R.; Passarelli, Michael N.; Foster, Cynthia Ewell; Merchant, Christopher R.
2017-01-01
This longitudinal study of recently hospitalized suicidal youth examined parental mental health history in addition to several indices of adolescent functioning as risk factors for time-to-suicide attempt over a 1-year period. Participants were 352 adolescents (253 girls, 99 boys; ages 13–17 years) who participated in self-report and interview assessments within 1 week of hospitalization and 6 weeks, 3, 6, and 12 months post-hospitalization. Multivariable proportional hazards regression modeled time-to-suicide attempt. Results indicate that adolescents were almost twice as likely to make a suicide attempt if they had at least one biological parent with mental health problems. Risk was also increased for adolescents with baseline histories of multiple previous suicide attempts, more severe suicidal ideation and more severe functional impairment. Findings suggest the need to consider the family system when intervening with suicidal youth. PMID:19967398
Smith, Patrick J.; Babyak, Michael A.; Mabe, Stephanie K.; Martinu, Tereza; Welty-Wolf, Karen E.; Emery, Charles F.; Palmer, Scott M.; Blumenthal, James A.
2015-01-01
Rationale: The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. Objectives: To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Methods: Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Measurements and Main Results: Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P = 0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P = 0.002). Conclusions: Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD. PMID:25568929
Rasmussen-Torvik, Laura J; Yatsuya, Hiroshi; Selvin, Elizabeth; Alonso, Alvaro; Folsom, Aaron R
2010-05-15
Previous studies have reported an association between circulating insulin and incident cardiovascular disease, but limited knowledge is available on the association across subgroups. We examined the associations of fasting insulin with incident coronary heart disease (CHD) and ischemic stroke in multiple subgroups of a biracial, middle-age cohort. A total of 12,323 subjects were included in the analysis. The incidence of CHD (n = 960) and ischemic stroke (n = 445) through 2005 was determined through annual interviews, repeat examinations, and community surveillance. Serum insulin was measured at baseline. Cox regression analysis was used to estimate the hazard ratios by quintile of fasting insulin at baseline and to determine the significance of effect modification. In the minimally adjusted models (age, gender, race, and field center), the baseline fasting insulin quintile was positively associated with both incident CHD (hazard ratio per quintile insulin = 1.12, p-trend <0.0001) and ischemic stroke (hazard ratio per quintile insulin = 1.11, p = 0.0018). The adjustment for high-density lipoprotein completely attenuated the association of insulin with CHD but not with stroke. The associations of insulin with CHD were stronger in nonsmokers (p-interaction = 0.018) and in those without hypertension (p-interaction = 0.0087). The associations of insulin with stroke were stronger in women (p-interaction = 0.037), whites (compared to blacks; p-interaction = 0.036), and those without hypertension (p-interaction = 0.0027). Copyright 2010 Elsevier Inc. All rights reserved.
Meuwese, Christiaan L.; Dekker, Friedo W.; Lindholm, Bengt; Qureshi, Abdul R.; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J.
2012-01-01
Summary Background and objectives Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. Design, setting, participants, & measurements In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models. Results During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Conclusions Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect. PMID:22246282
Meuwese, Christiaan L; Dekker, Friedo W; Lindholm, Bengt; Qureshi, Abdul R; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J
2012-01-01
Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan-Meier curves and Cox proportional hazard models. During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect.
Lêng, Chhian Hūi; Wang, Jung-Der
2016-01-01
To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50-64 years) and older (≥65 years) cohort in Taiwan. The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996-2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71-0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48-0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression.
Skier triggering of backcountry avalanches with skilled route selection
NASA Astrophysics Data System (ADS)
Sinickas, Alexandra; Haegeli, Pascal; Jamieson, Bruce
2015-04-01
Jamieson (2009) provided numerical estimates for the baseline probabilities of triggering an avalanche by a backcountry skier making fresh tracks without skilled route selection as a function of the North American avalanche danger scale (i.e., hazard levels Low, Moderate, Considerable, High and Extreme). Using the results of an expert survey, he showed that triggering probabilities while skiing directly up, down or across a trigger zone without skilled route selection increase roughly by a factor of 10 with each step of the North American avalanche danger scale (i.e. hazard level). The objective of the present study is to examine the effect of skilled route selection on the relationship between triggering probability and hazard level. To assess the effect of skilled route selection on triggering probability by hazard level, we analysed avalanche hazard assessments as well as reports of skiing activity and triggering of avalanches from 11 Canadian helicopter and snowcat operations during two winters (2012-13 and 2013-14). These reports were submitted to the daily information exchange among Canadian avalanche safety operations, and reflect professional decision-making and route selection practices of guides leading groups of skiers. We selected all skier-controlled or accidentally triggered avalanches with a destructive size greater than size 1 according to the Canadian avalanche size classification, triggered by any member of a guided group (guide or guest). These operations forecast the avalanche hazard daily for each of three elevation bands: alpine, treeline and below treeline. In contrast to the 2009 study, an exposure was defined as a group skiing within any one of the three elevation bands, and consequently within a hazard rating, for the day (~4,300 ratings over two winters). For example, a group that skied below treeline (rated Moderate) and treeline (rated Considerable) in one day, would receive one count for exposure to Moderate hazard, and one count for exposure to Considerable hazard. While the absolute values for triggering probability cannot be compared to the 2009 study because of different definitions of exposure, our preliminary results suggest that with skilled route selection the triggering probability is similar all hazard levels, except for extreme for which there are few exposures. This means that the guiding teams of backcountry skiing operations effectively control the hazard from triggering avalanches with skilled route selection. Groups were exposed relatively evenly to Low hazard (1275 times or 29% of total exposure), Moderate hazard (1450 times or 33 %) and Considerable hazard (1215 times or 28 %). At higher levels, the exposure reduced to roughly 380 times (9 % of total exposure) to High hazard, and only 13 times (0.3 %) to Extreme hazard. We assess the sensitivity of the results to some of our key assumptions.
The national alcohol helpline in Sweden: an evaluation of its first year
2014-01-01
Background Telephone helplines are easily available and can offer anonymity. Alcohol helplines may be a potential gateway to a more advanced support protocol, and they may function as a primary support option for some. However, although telephone helplines (quitlines) make up an established evidence-based support arena for smoking cessation, few studies have described such telephone-based alcohol counseling. Methods This study describes the basic characteristics of callers (n = 480) to the Swedish Alcohol Helpline during its first year of operation, and assesses aspects of change in alcohol behavior in a selected cohort of clients (n = 40) willing to abstain from anonymity and enter a proactive support protocol. Results During the study period, 50% of callers called for consultation regarding their own alcohol use (clients), a third called about relatives with alcohol problems, and the others called for information. The clients’ average age was 49 years, and half were females. The clients’ average AUDIT score at baseline was 21 (std. dev. =7.2). Approximately a quarter had scores indicating hazardous alcohol use at baseline, while the others had higher scores. In a follow-up pilot study, the average AUDIT score had decreased from 21 to 14. While clients reporting more severe alcohol use showed a significant decrease at follow-up, hazardous users exhibited no change during the study period. Conclusion The study indicates that telephone helplines addressing the general public can be a primary-care option to reduce risky alcohol use. A randomized controlled study is needed to control for the effect of spontaneous recovery. PMID:25015403
Analysis of BAG3 plasma concentrations in patients with acutely decompensated heart failure.
Gandhi, Parul U; Gaggin, Hanna K; Belcher, Arianna M; Harisiades, Jamie E; Basile, Anna; Falco, Antonia; Rosati, Alessandra; Piscione, Federico; Januzzi, James L; Turco, M Caterina
2015-05-20
BCL-2-associated athanogene 3 (BAG3) is a protein implicated in the cardiomyocyte stress response and genesis of cardiomyopathy. Extracellular BAG3 is measurable in patients with heart failure (HF), but the relationship of BAG3 with HF prognosis is unclear. BAG3 plasma concentrations were measured in 39 acutely decompensated HF patients; the primary endpoint was death at 1 year. Baseline characteristics were compared by vital status and median BAG3 concentration. Correlation of BAG3 with left ventricular ejection fraction (LVEF) and other biomarkers was performed. Prognostic value was assessed using Cox proportional hazards regression and Kaplan-Meier analysis. At baseline, median BAG3 was significantly higher in decedents (N=11) than survivors (N=28; 1489 ng/mL versus 50 ng/mL; P=0.04); decedents also had worse renal function and higher median natriuretic peptide (NP) and sST2. BAG3 was not significantly correlated with NPs, mid-regional pro-adrenomedullin, sST2, or eGFR, however. Mortality was increased in patients with supra-median BAG3 (>336 ng/mL; 42.1% versus 15.0%, P=0.06). In age and LVEF-adjusted Cox proportional hazards, BAG3 remained a significant mortality predictor (HR=3.20; 95% CI=1.34-7.65; P=0.02); those with supra-median BAG3 had significantly shorter time-to-death (P=0.04). The stress response protein BAG3 is measurable in patients with ADHF and may be prognostic for death. Copyright © 2015 Elsevier B.V. All rights reserved.
Socioeconomic Status, Structural and Functional Measures of Social Support, and Mortality
Stringhini, Silvia; Berkman, Lisa; Dugravot, Aline; Ferrie, Jane E.; Marmot, Michael; Kivimaki, Mika; Singh-Manoux, Archana
2012-01-01
The authors examined the associations of social support with socioeconomic status (SES) and with mortality, as well as how SES differences in social support might account for SES differences in mortality. Analyses were based on 9,333 participants from the British Whitehall II Study cohort, a longitudinal cohort established in 1985 among London-based civil servants who were 35–55 years of age at baseline. SES was assessed using participant's employment grades at baseline. Social support was assessed 3 times in the 24.4-year period during which participants were monitored for death. In men, marital status, and to a lesser extent network score (but not low perceived support or high negative aspects of close relationships), predicted both all-cause and cardiovascular mortality. Measures of social support were not associated with cancer mortality. Men in the lowest SES category had an increased risk of death compared with those in the highest category (for all-cause mortality, hazard ratio = 1.59, 95% confidence interval: 1.21, 2.08; for cardiovascular mortality, hazard ratio = 2.48, 95% confidence interval: 1.55, 3.92). Network score and marital status combined explained 27% (95% confidence interval: 14, 43) and 29% (95% confidence interval: 17, 52) of the associations between SES and all-cause and cardiovascular mortality, respectively. In women, there was no consistent association between social support indicators and mortality. The present study suggests that in men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES. PMID:22534202
NASA Technical Reports Server (NTRS)
Lowman, P. D.; Allenby, R. J.; Frey, H. V.
1979-01-01
Recommendations are presented for a global network of 125 sites for geodetic measurements by satellite laser ranging and very long baseline interferometry. The sites were proposed on the basis of existing facilities and scientific value for investigation of crustal dynamics as related to earthquake hazards. Tectonic problems are discussed for North America peripheral regions and for the world. The sites are presented in tables and maps, with bibliographic references.
flexsurv: A Platform for Parametric Survival Modeling in R
Jackson, Christopher H.
2018-01-01
flexsurv is an R package for fully-parametric modeling of survival data. Any parametric time-to-event distribution may be fitted if the user supplies a probability density or hazard function, and ideally also their cumulative versions. Standard survival distributions are built in, including the three and four-parameter generalized gamma and F distributions. Any parameter of any distribution can be modeled as a linear or log-linear function of covariates. The package also includes the spline model of Royston and Parmar (2002), in which both baseline survival and covariate effects can be arbitrarily flexible parametric functions of time. The main model-fitting function, flexsurvreg, uses the familiar syntax of survreg from the standard survival package (Therneau 2016). Censoring or left-truncation are specified in ‘Surv’ objects. The models are fitted by maximizing the full log-likelihood, and estimates and confidence intervals for any function of the model parameters can be printed or plotted. flexsurv also provides functions for fitting and predicting from fully-parametric multi-state models, and connects with the mstate package (de Wreede, Fiocco, and Putter 2011). This article explains the methods and design principles of the package, giving several worked examples of its use. PMID:29593450
Abebe, Gumataw K; Chalak, Ali; Abiad, Mohamad G
2017-07-01
Food safety is a key public health issue worldwide. This study aims to characterise existing governance mechanisms - governance structures (GSs) and food safety management systems (FSMSs) - and analyse the alignment thereof in detecting food safety hazards, based on empirical evidence from Lebanon. Firm-to-firm and public baseline are the dominant FSMSs applied in a large-scale, while chain-wide FSMSs are observed only in a small-scale. Most transactions involving farmers are relational and market-based in contrast to (large-scale) processors, which opt for hierarchical GSs. Large-scale processors use a combination of FSMSs and GSs to minimise food safety hazards albeit potential increase in coordination costs; this is an important feature of modern food supply chains. The econometric analysis reveals contract period, on-farm inspection and experience having significant effects in minimising food safety hazards. However, the potential to implement farm-level FSMS is influenced by formality of the contract, herd size, trading partner choice, and experience. Public baseline FSMSs appear effective in controlling food safety hazards; however, this may not be viable due to the scarcity of public resources. We suggest public policies to focus on long-lasting governance mechanisms by introducing incentive schemes and farm-level FSMSs by providing loans and education to farmers. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Klein, Jonathan, E-mail: jonathan.klein@rmp.uhn.on.ca; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario; Dawson, Laura A.
Purpose: To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver. Methods and Materials: Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were alsomore » treated. Results: The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P=.17) or overall survival (P=.088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT-Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P=.001) and 0.88 (95% CI 0.82-0.95; P=.001), respectively. Tumor size was inversely correlated with survival. Conclusions: Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and warrants comparison against other liver-directed therapies.« less
Parashos, Sotirios A; Luo, Sheng; Biglan, Kevin M; Bodis-Wollner, Ivan; He, Bo; Liang, Grace S; Ross, G Webster; Tilley, Barbara C; Shulman, Lisa M
2014-06-01
Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy. AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change. clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.
Risk factors for stent graft thrombosis after transjugular intrahepatic portosystemic shunt creation
Jahangiri, Younes; Kerrigan, Timothy; Li, Lei; Prosser, Dominik; Brar, Anantnoor; Righetti, Johnathan; Schenning, Ryan C.; Kaufman, John A.
2017-01-01
Background To identify risk factors of stent graft thrombosis after transjugular intrahepatic portosystemic shunt (TIPS) creation. Methods Patients who underwent TIPS creation between June 2003 and January 2016 and with follow-up assessing stent graft patency were included (n=174). Baseline comorbidities, liver function, procedural details and follow-up liver function tests were analyzed in association with hazards of thrombosis on follow-up. Competing risk cox regression models were used considering liver transplant after TIPS creation as the competing risk variable. Results One-, 2- and 5-year primary patency rates were 94.1%, 91.7% and 78.2%, respectively. Patient age [sub-hazard ratio (sHR): 1.13; P=0.001], body mass index (BMI) <30 (sHR: 33.08; P=0.008) and a higher post-TIPS portosystemic pressure gradient (sHR: 1.14; P=0.023) were significantly associated with TIPS thrombosis in multivariate analysis. A higher rate of TIPS thrombosis was observed in those for whom the procedure was clinically unsuccessful (P=0.014). A significant increase in incidence of thrombosis was noted with increasing tertiles of post-TIPS portosystemic gradients (P value for trend=0.017). Conclusions Older age, lower BMI and higher post-TIPS portosystemic gradients were associated with higher hazards of shunt thrombosis after TIPS creation using stent grafts. Higher rates of shunt thrombosis were seen in patients for whom TIPS creation was clinically unsuccessful. The association between TIPS thrombosis and higher post-TIPS portosystemic gradients may indicate impaired flow through the shunt, a finding which may be technical or anatomic in nature and should be assessed before procedure completion. PMID:29399518
Cigarette Smoking and Incident Heart Failure: Insights From the Jackson Heart Study.
Kamimura, Daisuke; Cain, Loretta R; Mentz, Robert J; White, Wendy B; Blaha, Michael J; DeFilippis, Andrew P; Fox, Ervin R; Rodriguez, Carlos J; Keith, Rachel J; Benjamin, Emelia J; Butler, Javed; Bhatnagar, Aruni; Robertson, Rose M; Winniford, Michael D; Correa, Adolfo; Hall, Michael E
2018-06-12
Cigarette smoking has been linked with several factors associated with cardiac dysfunction. We hypothesized that cigarette smoking is associated with left ventricular (LV) structure and function, and incident heart failure (HF) hospitalization. We investigated 4129 (never smoker n=2884, current smoker n=503, and former smoker n=742) black participants (mean age, 54 years; 63% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the relationships between cigarette smoking and LV structure and function by using cardiac magnetic resonance imaging among 1092 participants, cigarette smoking and brain natriuretic peptide levels among 3325 participants, and incident HF hospitalization among 3633 participants with complete data. After adjustment for confounding factors, current smoking was associated with higher mean LV mass index and lower mean LV circumferential strain ( P <0.05, for both) in comparison with never smoking. Smoking status, intensity, and burden were associated with higher mean brain natriuretic peptide levels (all P <0.05). Over 8.0 years (7.7-8.0) median follow-up, there were 147 incident HF hospitalizations. After adjustment for traditional risk factors and incident coronary heart disease, current smoking (hazard ratio, 2.82; 95% confidence interval, 1.71-4.64), smoking intensity among current smokers (≥20 cigarettes/d: hazard ratio, 3.48; 95% confidence interval, 1.65-7.32), and smoking burden among ever smokers (≥15 pack-years: hazard ratio, 2.06; 95% confidence interval, 1.29-3.3) were significantly associated with incident HF hospitalization in comparison with never smoking. In blacks, cigarette smoking is an important risk factor for LV hypertrophy, systolic dysfunction, and incident HF hospitalization even after adjusting for effects on coronary heart disease. © 2018 American Heart Association, Inc.
Konishi, S; Ng, C F S; Stickley, A; Watanabe, C
2016-08-01
Having an allergic disease may have health implications beyond those more commonly associated with allergy given that previous epidemiological studies have suggested that both atopy and allergy are linked to mortality. More viable immune functioning among the elderly, as indicated by the presence of an allergic disease, might therefore be associated with differences in all-cause mortality. Using data from a Japanese cohort, this study examined whether having pollinosis (a form of allergic rhinitis) in a follow-up survey could predict all-cause and cause-specific mortality. Data came from the Komo-Ise cohort, which at its 1993 baseline recruited residents aged 40-69 years from two areas in Gunma prefecture, Japan. The current study used information on pollinosis that was obtained from the follow-up survey in 2000. Mortality and migration data were obtained throughout the follow-up period up to December 2008. Proportional hazard models were used to examine the relation between pollinosis and mortality. At the 2000 follow-up survey, 12% (1088 of 8796) of respondents reported that they had pollinosis symptoms in the past 12 months. During the 76 186 person-years of follow-up, 748 died from all causes. Among these, there were 37 external, 208 cardiovascular, 74 respiratory, and 329 neoplasm deaths. After adjusting for potential confounders, pollinosis was associated with significantly lower all-cause [hazard ratio 0.57 (95% confidence interval = 0.38-0.87)] and neoplasms mortality [hazard ratio 0.48 (95% confidence interval = 0.26-0.92)]. Having an allergic disease (pollinosis) at an older age may be indicative of more viable immune functioning and be protective against certain causes of death. Further research is needed to determine the possible mechanisms underlying the association between pollinosis and mortality. © 2015 John Wiley & Sons Ltd.
Shomura, Masako; Kagawa, Tatehiro; Okabe, Haruka; Shiraishi, Koichi; Hirose, Shunji; Arase, Yoshitaka; Tsuruya, Kota; Takahira, Sachiko; Mine, Tetsuya
2016-11-11
This study aimed to identify the health-related quality of life (HRQOL) domains associated with prognosis by assessing longitudinal alterations in HRQOL in patients with advanced hepatocellular carcinoma receiving sorafenib. We prospectively assessed HRQOL by administering the SF-36 questionnaire 3-monthly to consecutive patients with advanced hepatocellular carcinoma receiving sorafenib. We evaluated the impact of HRQOL on their overall survival and duration of treatment with sorafenib using Cox's proportional hazards model. There were 54 participants: 42 (78 %) were male, the median age was 71 years, 24 (44 %) had hepatitis C virus infection, 33 (61 %) had Child-Pugh scores of 5, and 30 (56 %) had TNM stage IV hepatocellular carcinoma. The median overall survival and treatment duration were 9 and 5 months, respectively, and 40 patients (74 %) died. Thirteen patients receiving sorafenib over a 1-year period maintained all domain scores >40, without a significant decline during the treatment period. In contrast, physical functioning, physical role, and vitality scores declined continuously and significantly in the year before death (in the 40 patients who died). Previous curative treatment and physical functioning scores ≥40 at baseline were significantly associated with longer overall survival by multivariate analysis. Social functioning scores ≥40, absence of vascular invasion, and lower DCP value were significant predictors of longer treatment duration. HRQOL was not significantly impaired in those patients who were able to complete a 1-year course of sorafenib treatment. Baseline physical functioning scores ≥40 and social functioning scores ≥40 were significantly associated with longer overall survival and longer treatment duration, respectively. Thus, HRQOL could be a valuable marker to predict the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib.
Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women
Huang, Alison J.; Sawaya, George F.; Vittinghoff, Eric; Lin, Feng; Grady, Deborah
2010-01-01
Objective The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. Methods We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes “some” to ”all” of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. Results The mean age of participants was 66.7 ± 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. Conclusions Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes. PMID:19325499
Naudin, Sabine; Li, Kuanrong; Jaouen, Tristan; Assi, Nada; Kyrø, Cecilie; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Védié, Anne-Laure; Boeing, Heiner; Kaaks, Rudolf; Katzke, Verena; Bamia, Christina; Naska, Androniki; Trichopoulou, Antonia; Berrino, Franco; Tagliabue, Giovanna; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Peeters, Petra H; Bueno-de-Mesquita, H B As; Weiderpass, Elisabete; Gram, Inger Torhild; Skeie, Guri; Chirlaque, Maria-Dolores; Rodríguez-Barranco, Miguel; Barricarte, Aurelio; Quirós, Jose Ramón; Dorronsoro, Miren; Johansson, Ingegerd; Sund, Malin; Sternby, Hanna; Bradbury, Kathryn E; Wareham, Nick; Riboli, Elio; Gunter, Marc; Brennan, Paul; Duell, Eric J; Ferrari, Pietro
2018-03-09
Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake. © 2018 IARC/WHO.
Meng, G; Yang, H; Bao, X; Zhang, Q; Liu, L; Wu, H; Du, H; Xia, Y; Shi, H; Guo, X; Liu, X; Li, C; Su, Q; Gu, Y; Fang, L; Yu, F; Sun, S; Wang, X; Zhou, M; Jia, Q; Guo, Q; Song, K; Huang, G; Wang, G; Wu, Y; Niu, K
2017-04-01
To comprehensively and exhaustively assess the relationship between serum ferritin levels and incidence of prediabetes in a prospective study. This prospective cohort study (n=7380) with a mean follow-up of 3.07 years (range: 1-7, 95% CI: 3.03-3.12) was conducted in Tianjin, China. Blood fasting glucose, oral glucose tolerance test, serum ferritin levels and other potentially confounding factors were measured at baseline and at each year of follow-up. Adjusted Cox proportional hazards regression models were used to assess the gender-specific relationship between baseline and mean serum ferritin quintiles and prediabetes. The incidence of prediabetes was 85 per 1000 person-years among men and 44 per 1000 person-years among women during follow-up (from 2007 to 2014). After adjusting for potential confounders, hazard ratios (95% CI) for prediabetes across baseline ferritin quintiles were: for men, 1.00, 1.13 (0.90-1.40), 1.20 (0.97-1.48), 1.41 (1.14-1.73) and 1.73 (1.41-2.11); and for women, 1.00, 1.01 (0.74-1.38), 0.68 (0.48-0.96), 0.84 (0.61-1.15) and 1.07 (0.80-1.45), respectively. Similar results were also observed for mean ferritin levels. Both baseline and mean serum ferritin levels were significantly and linearly related to prediabetes in men, whereas U-shaped relationships were observed between baseline and mean serum ferritin and prediabetes in women. The relationship between prediabetes risk and mean serum ferritin levels may be more stable than one with baseline serum ferritin levels. Copyright © 2016. Published by Elsevier Masson SAS.
Depression and incident dementia. An 8-year population-based prospective study.
Luppa, Melanie; Luck, Tobias; Ritschel, Franziska; Angermeyer, Matthias C; Villringer, Arno; Riedel-Heller, Steffi G
2013-01-01
The aim of the study was to investigate the impact of depression (categorical diagnosis; major depression, MD) and depressive symptoms (dimensional diagnosis and symptom patterns) on incident dementia in the German general population. Within the Leipzig Longitudinal Study of the Aged (LEILA 75+), a representative sample of 1,265 individuals aged 75 years and older were interviewed every 1.5 years over 8 years (mean observation time 4.3 years; mean number of visits 4.2). Cox proportional hazards and binary logistic regressions were used to estimate the effect of baseline depression and depressive symptoms on incident dementia. The incidence of dementia was 48 per 1,000 person-years (95% confidence interval (CI) 45-51). Depressive symptoms (Hazard ratio HR 1.03, 95% CI 1.01-1.05), and in particular mood-related symptoms (HR 1.08, 95% CI 1.03-1.14), showed a significant impact on the incidence of dementia only in univariate analysis, but not after adjustment for cognitive and functional impairment. MD showed only a significant impact on incidence of dementia in Cox proportional hazards regression, but not in binary logistic regression models. The present study using different diagnostic measures of depression on future dementia found no clear significant associations of depression and incident dementia. Further in-depth investigation would help to understand the nature of depression in the context of incident dementia.
Ricci, Cristian; Wood, Angela; Muller, David; Gunter, Marc J; Agudo, Antonio; Boeing, Heiner; van der Schouw, Yvonne T; Warnakula, Samantha; Saieva, Calogero; Spijkerman, Annemieke; Sluijs, Ivonne; Tjønneland, Anne; Kyrø, Cecilie; Weiderpass, Elisabete; Kühn, Tilman; Kaaks, Rudolf; Sánchez, Maria-Jose; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Engström, Gunnar; Melander, Olle; Bonnet, Fabrice; Boer, Jolanda M A; Key, Timothy J; Travis, Ruth C; Overvad, Kim; Verschuren, W M Monique; Quirós, J Ramón; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Peppa, Eleni; Iribas, Conchi Moreno; Gavrila, Diana; Forslund, Ann-Sofie; Jansson, Jan-Håkan; Matullo, Giuseppe; Arriola, Larraitz; Freisling, Heinz; Lassale, Camille; Tzoulaki, Ioanna; Sharp, Stephen J; Forouhi, Nita G; Langenberg, Claudia; Saracci, Rodolfo; Sweeting, Michael; Brennan, Paul; Butterworth, Adam S; Riboli, Elio; Wareham, Nick J; Danesh, John; Ferrari, Pietro
2018-05-29
To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Multicentre case-cohort study. A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Communicating Volcanic Hazards in the North Pacific
NASA Astrophysics Data System (ADS)
Dehn, J.; Webley, P.; Cunningham, K. W.
2014-12-01
For over 25 years, effective hazard communication has been key to effective mitigation of volcanic hazards in the North Pacific. These hazards are omnipresent, with a large event happening in Alaska every few years to a decade, though in many cases can happen with little or no warning (e.g. Kasatochi and Okmok in 2008). Here a useful hazard mitigation strategy has been built on (1) a large database of historic activity from many datasets, (2) an operational alert system with graduated levels of concern, (3) scenario planning, and (4) routine checks and communication with emergency managers and the public. These baseline efforts are then enhanced in the time of crisis with coordinated talking points, targeted studies and public outreach. Scientists naturally tend to target other scientists as their audience, whereas in effective monitoring of hazards that may only occur on year to decadal timescales, details can distract from the essentially important information. Creating talking points and practice in public communications can help make hazard response a part of the culture. Promoting situational awareness and familiarity can relieve indecision and concerns at the time of a crisis.
Anema, Johannes R; Steenstra, Ivan A; Bongers, Paulien M; de Vet, Henrica C W; Knol, Dirk L; Loisel, Patrick; van Mechelen, Willem
2007-02-01
Population-based randomized controlled trial. To assess the effectiveness of workplace intervention and graded activity, separately and combined, for multidisciplinary rehabilitation of low back pain (LBP). Effective components for multidisciplinary rehabilitation of LBP are not yet established. Participants sick-listed 2 to 6 weeks due to nonspecific LBP were randomized to workplace intervention (n = 96) or usual care (n = 100). Workplace intervention consisted of workplace assessment, work modifications, and case management involving all stakeholders. Participants still sick-listed at 8 weeks were randomized for graded activity (n = 55) or usual care (n = 57). Graded activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles. Outcomes were lasting return to work, pain intensity and functional status, assessed at baseline, and at 12, 26, and 52 weeks after the start of sick leave. Time until return to work for workers with workplace intervention was 77 versus 104 days (median) for workers without this intervention (P = 0.02). Workplace intervention was effective on return to work (hazard ratio = 1.7; 95% CI, 1.2-2.3; P = 0.002). Graded activity had a negative effect on return to work (hazard ratio = 0.4; 95% CI, 0.3-0.6; P < 0.001) and functional status. Combined intervention had no effect. Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP. Graded activity or combined intervention is not advised.
Failing, Jarrett J; Yan, Yiyi; Porrata, Luis F; Markovic, Svetomir N
2017-12-01
The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it has not been studied in patients treated with immune checkpoint inhibitors. In this study, we analyzed the baseline LMR with progression-free survival (PFS) and overall survival (OS) in metastatic melanoma patients treated with pembrolizumab. A total of 133 patients with metastatic melanoma treated with pembrolizumab were included in this retrospective study. LMR was calculated from pretherapy peripheral blood counts and the optimal cutoff value was determined by a receiver operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazard modeling. Patients with an LMR of at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval: 0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15-0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic melanoma patients treated with pembrolizumab, and could represent a convenient and cost-effective prognostic biomarker. Validation of these findings in an independent cohort is needed.
Moe, Sharon M; Chertow, Glenn M; Parfrey, Patrick S; Kubo, Yumi; Block, Geoffrey A; Correa-Rotter, Ricardo; Drüeke, Tilman B; Herzog, Charles A; London, Gerard M; Mahaffey, Kenneth W; Wheeler, David C; Stolina, Maria; Dehmel, Bastian; Goodman, William G; Floege, Jürgen
2015-07-07
Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events. This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99). Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839. © 2015 American Heart Association, Inc.
Time frequency requirements for radio interferometric earth physics
NASA Technical Reports Server (NTRS)
Thomas, J. B.; Fliegel, H. F.
1973-01-01
Two systems of VLBI (Very Long Baseline Interferometry) are now applicable to earth physics: an intercontinental baseline system using antennas of the NASA Deep Space Network, now observing at one-month intervals to determine UTI for spacecraft navigation; and a shorter baseline system called ARIES (Astronomical Radio Interferometric Earth Surveying), to be used to measure crustal movement in California for earthquake hazards estimation. On the basis of experience with the existing DSN system, a careful study has been made to estimate the time and frequency requirements of both the improved intercontinental system and of ARIES. Requirements for the two systems are compared and contrasted.
van Loon, I N; Bots, M L; Boereboom, F T J; Grooteman, M P C; Blankestijn, P J; van den Dorpel, M A; Nubé, M J; Ter Wee, P M; Verhaar, M C; Hamaker, M E
2017-07-06
Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients. This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality. Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups. In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients.
Tea consumption and mortality in the oldest-old Chinese.
Ruan, Rongping; Feng, Lei; Li, Jialiang; Ng, Tze-Pin; Zeng, Yi
2013-11-01
To investigate the association between tea consumption and mortality in the oldest-old Chinese. Population-based longitudinal data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed using a Cox semiparametric proportional hazard model. Six hundred thirty-one randomly selected counties and cities of China's 22 provinces. Individuals aged 80 and older (N = 9,093) who provided complete data in the baseline survey (1998). Self-reported current frequency of tea drinking and past frequency at approximately age 60 were ascertained at baseline survey; a follow-up survey was conducted 2000, 2002, and 2005. In the oldest-old Chinese, tea consumption was associated with lower risk of mortality after adjusting for demographic characteristics, socioeconomic status, health practices, and health status. Compared with non-tea drinkers, the adjusted hazard ratio (HR) was 0.90 (95% confidence interval (CI) = 0.84-0.96) for daily tea drinkers (at the baseline survey, 1998) and 1.00 (95% CI = 1.01-1.07) for occasional tea drinkers (P for linear trend .003). Similar results were found when tea drinking status at age 60 was used in the analysis. Further analysis showed that subjects who reported frequent tea drinking at age 60 and at the baseline survey had a 10% lower risk of mortality than subjects who reported infrequent tea drinking at age 60 and at the baseline survey (HR = 0.90, 95% CI = 0.84-0.97). Tea consumption is associated with lower risk of mortality in the oldest-old Chinese. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.
Heikkilä, Katriina; Madsen, Ida E H; Nyberg, Solja T; Fransson, Eleonor I; Ahola, Kirsi; Alfredsson, Lars; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Ferrie, Jane E; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Nielsen, Martin L; Nordin, Maria; Pejtersen, Jan H; Pentti, Jaana; Rugulies, Reiner; Oksanen, Tuula; Shipley, Martin J; Suominen, Sakari B; Theorell, Töres; Väänänen, Ari; Vahtera, Jussi; Virtanen, Marianna; Westerlund, Hugo; Westerholm, Peter J M; Batty, G David; Singh-Manoux, Archana; Kivimäki, Mika
2014-01-01
Many clinicians, patients and patient advocacy groups believe stress to have a causal role in inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. However, this is not corroborated by clear epidemiological research evidence. We investigated the association between work-related stress and incident Crohn's disease and ulcerative colitis using individual-level data from 95,000 European adults. We conducted individual-participant data meta-analyses in a set of pooled data from 11 prospective European studies. All studies are a part of the IPD-Work Consortium. Work-related psychosocial stress was operationalised as job strain (a combination of high demands and low control at work) and was self-reported at baseline. Crohn's disease and ulcerative colitis were ascertained from national hospitalisation and drug reimbursement registers. The associations between job strain and inflammatory bowel disease outcomes were modelled using Cox proportional hazards regression. The study-specific results were combined in random effects meta-analyses. Of the 95,379 participants who were free of inflammatory bowel disease at baseline, 111 men and women developed Crohn's disease and 414 developed ulcerative colitis during follow-up. Job strain at baseline was not associated with incident Crohn's disease (multivariable-adjusted random effects hazard ratio: 0.83, 95% confidence interval: 0.48, 1.43) or ulcerative colitis (hazard ratio: 1.06, 95% CI: 0.76, 1.48). There was negligible heterogeneity among the study-specific associations. Our findings suggest that job strain, an indicator of work-related stress, is not a major risk factor for Crohn's disease or ulcerative colitis.
Lêng, Chhian Hūi; Wang, Jung-Der
2016-01-01
Aims To test the hypothesis that gardening is beneficial for survival after taking time-dependent comorbidities, mobility, and depression into account in a longitudinal middle-aged (50–64 years) and older (≥65 years) cohort in Taiwan. Methods The cohort contained 5,058 nationally sampled adults ≥50 years old from the Taiwan Longitudinal Study on Aging (1996–2007). Gardening was defined as growing flowers, gardening, or cultivating potted plants for pleasure with five different frequencies. We calculated hazard ratios for the mortality risks of gardening and adjusted the analysis for socioeconomic status, health behaviors and conditions, depression, mobility limitations, and comorbidities. Survival models also examined time-dependent effects and risks in each stratum contingent upon baseline mobility and depression. Sensitivity analyses used imputation methods for missing values. Results Daily home gardening was associated with a high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71–0.94). The benefits were robust for those with mobility limitations, but without depression at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48–0.87) when adjusted for time-dependent comorbidities, mobility limitations, and depression. Chronic or relapsed depression weakened the protection of gardening. For those without mobility limitations and not depressed at baseline, gardening had no effect. Sensitivity analyses using different imputation methods yielded similar results and corroborated the hypothesis. Conclusion Daily gardening for pleasure was associated with reduced mortality for Taiwanese >50 years old with mobility limitations but without depression. PMID:27486315
Wassertheil-Smoller, Sylvia; McGinn, Aileen P.; Martin, Lisa; Rodriguez, Beatriz L.; Stefanick, Marcia L.; Perez, Marco
2017-01-01
Abstract Atrial fibrillation (AF) is a common arrhythmia that poses a significant risk of stroke. Cross-sectional and case-control studies have shown evidence of associations between AF and breast or colorectal cancer, but there have been no longitudinal studies in which this has been assessed. We prospectively examined a cohort of 93,676 postmenopausal women enrolled in the Women's Health Initiative from 1994 to 1998 to determine whether there are relationships between baseline AF and the development of invasive breast or colorectal cancer. The prevalence of self-reported physician diagnosis of AF at baseline was 5.1%. Over approximately 15 years of follow-up, the incidence of invasive breast cancer was 5.7%, and the incidence of colorectal cancer was 1.6%. Adjusted hazard ratios and 95% confidence intervals were obtained using Cox proportional hazards models. We found no significant association between AF and incident colorectal cancer, but we did see a 19% excess risk of invasive breast cancer among those with AF (adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.03, 1.38). Additional adjustment for baseline use of cardiac glycosides attenuated the association between AF and invasive breast cancer (HR = 1.01, 95% CI: 0.85, 1.20). Cardiac glycoside use was strongly associated with incident invasive breast cancer (HR = 1.68, 95% CI: 1.33, 2.12) independent of AF and other confounders. Mechanisms of the associations among breast cancer, AF, and cardiac glycosides need further investigation. PMID:28174828
The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital.
Forster, Alan J; Taljaard, Monica; Oake, Natalie; Wilson, Kumanan; Roth, Virginia; van Walraven, Carl
2012-01-10
The effect of hospital-acquired infection with Clostridium difficile on length of stay in hospital is not yet fully understood. We determined the independent impact of hospital-acquired infection with C. difficile on length of stay in hospital. We conducted a retrospective observational cohort study of admissions to hospital between July 1, 2002, and Mar. 31, 2009, at a single academic hospital. We measured the association between infection with hospital-acquired C. difficile and time to discharge from hospital using Kaplan-Meier methods and a Cox multivariable proportional hazards regression model. We controlled for baseline risk of death and accounted for C. difficile as a time-varying effect. Hospital-acquired infection with C. difficile was identified in 1393 of 136,877 admissions to hospital (overall risk 1.02%, 95% confidence interval [CI] 0.97%-1.06%). The crude median length of stay in hospital was greater for patients with hospital-acquired C. difficile (34 d) than for those without C. difficile (8 d). Survival analysis showed that hospital-acquired infection with C. difficile increased the median length of stay in hospital by six days. In adjusted analyses, hospital-acquired C. difficile was significantly associated with time to discharge, modified by baseline risk of death and time to acquisition of C. difficile. The hazard ratio for discharge by day 7 among patients with hospital-acquired C. difficile was 0.55 (95% CI 0.39-0.70) for patients in the lowest decile of baseline risk of death and 0.45 (95% CI 0.32-0.58) for those in the highest decile; for discharge by day 28, the corresponding hazard ratios were 0.74 (95% CI 0.60-0.87) and 0.61 (95% CI 0.53-0.68). Hospital-acquired infection with C. difficile significantly prolonged length of stay in hospital independent of baseline risk of death.
Hoke, Robert S; Müller-Werdan, Ursula; Lautenschläger, Christine; Werdan, Karl; Ebelt, Henning
2012-02-01
To study the association between baseline heart rate and outcome in patients with multiple organ dysfunction (MODS) as well as the course of heart rate over the first 4 days during MODS. Prospective observational study in 89 patients with MODS, defined as an APACHE-II score ≥20. Baseline heart rate (HR(0)) was determined over a 60-minute period at the time of MODS diagnosis. 28-day all-cause mortality was the primary endpoint of the study, a fall of the APACHE-II score by 4 points or more from day 0 to day 4 constituted the secondary endpoint. Hazard ratios for heart rate of 90 beats per minute (bpm) or greater relative to less than 90 bpm were calculated using Cox proportional hazards model and adjusted for confounding variables. Median baseline heart rate was 83 bpm in survivors and 92 bpm in non-survivors (p = 0.048). 28-day mortality was 32 and 61% in patients with HR(0) < 90 bpm and HR(0) ≥ 90 bpm, respectively. The adjusted hazard ratio for 28-day mortality was 2.30 (95% confidence interval 1.21-4.36, p = 0.001) for HR(0) ≥ 90 bpm relative to HR(0) < 90 bpm. No correlation was found between baseline heart rate and the secondary endpoint. From day 0 to day 4, heart rate remained elevated in all patients, as well as in survivors and non-survivors. A heart rate ≥90 bpm at the time of MODS diagnosis is an independent risk factor for increased 28-day mortality. As in patients with cardiovascular conditions such as coronary heart disease or chronic heart failure, heart rate might constitute a target for heart rate-lowering therapy in the narrow initial treatment window of MODS.
Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R
2017-04-01
Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P < 0.0001; mean difference = -0.03 with 95% limits of agreement of -0.19 to 0.14). Baseline extent of GGR was independently associated with disease progression when adjusting for baseline Gender-Age-Physiology stage and smoking status (hazard ratio per 10% visual GGR increase = 1.98, 95% confidence interval [CI] = 1.20-3.28, P = 0.008; and hazard ratio per 10% AMFM GGR increase = 1.36, 95% CI = 1.01-1.84, P = 0.04). Postbaseline visual and AMFM GGR trajectories were correlated with postbaseline FVC trajectory (r = -0.30, 95% CI = -0.46 to -0.11, P = 0.002; and r = -0.25, 95% CI = -0.42 to -0.06, P = 0.01, respectively). More extensive baseline visual and AMFM fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.
Pilotto, Jose H; Velasque, Luciane S; Friedman, Ruth K; Moreira, Ronaldo I; Veloso, Valdilea G; Grinsztejn, Beatriz; Morgado, Mariza G; Watts, D Heather; Currier, Judith S; Hoffman, Risa M
2011-01-01
Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to ≤200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models. A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline ≥500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02). In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.
Al-Batran, S.-E.; Van Cutsem, E.; Oh, S. C.; Bodoky, G.; Shimada, Y.; Hironaka, S.; Sugimoto, N.; Lipatov, O. N.; Kim, T.-Y.; Cunningham, D.; Rougier, P.; Muro, K.; Liepa, A. M.; Chandrawansa, K.; Emig, M.; Ohtsu, A.; Wilke, H.
2016-01-01
Background The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine–platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients and methods Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m2) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Results Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. Conclusion In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. ClinicalTrials.gov NCT01170663. PMID:26747859
Analysis of Participant Withdrawal in Huntington Disease Clinical Trials.
Banno, Haruhiko; Andrzejewski, Kelly L; McDermott, Michael P; Murphy, Alyssa; Majumder, Madhurima; de Blieck, Elisabeth A; Auinger, Peggy; Cudkowicz, Merit E; Atassi, Nazem
2017-01-01
Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials. We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal. Analyses of participant withdrawal were performed for three randomized, double-blind, placebo-controlled trials including the CARE-HD (coenzyme Q10 and remacemide in HD, n = 347), DOMINO (pilot study of minocycline in HD, n = 114), and 2CARE (coenzyme Q10 in HD, n = 609) trials. Reasons for withdrawal were obtained by review of textual data in the study databases. Participant demographic and clinical characteristics were analyzed as potential predictors of time to withdrawal using Cox-proportional hazards models. Estimated probabilities of withdrawal at 12 months were 2.9% for CARE-HD, 10.5% for DOMINO, and 5.9% for 2CARE. The top reasons for withdrawal (202 in total), expressed as mean percentage across the three trials, were loss to follow-up (23.2%), death (15.9%), and loss of interest/desire to participate (15.2%). Baseline and time-dependent variables associated with time to withdrawal were mainly motor, behavioral, and functional scores. Age, gender, ethnicity, and educational level were not associated with time to withdrawal in any of the three studies. The estimated withdrawal probability at 12 months ranged from 2.9% to 10.5% in the three HD trials considered here. A possible strategy to improve retention of participants in future HD clinical trials is to enroll individuals with higher baseline functional and behavioral status.
Park, Sehoon; Lee, Soojin; Lee, Anna; Paek, Jin Hyuk; Chin, Ho Jun; Na, Ki Young; Chae, Dong-Wan; Kim, Sejoong
2018-05-01
It is unclear whether pathologic findings on preoperative urinalysis are associated with the risk of postoperative acute kidney injury (AKI). Therefore, we performed a retrospective review to investigate this association. We assessed the clinical significance of preoperative dipstick urinalysis in a 10-year surgery cohort from a tertiary hospital in Korea. Patients without available information on perioperative serum creatinine levels or kidney injury prior to surgery were excluded. Preoperative dipstick urinalysis parameters, including albuminuria, hematuria, pyuria, and others were studied. The primary outcome was postoperative acute kidney injury. Secondary outcomes were postoperative 1-year mortality and progression of poor kidney function parameters. We enrolled 40,090 patients. The presence of dipstick albuminuria was associated with an increased risk of postoperative AKI (adjusted odds ratio 1.47 [1.29-1.66], P < .001), and the association showed a dose-response relationship. High specific gravity was significantly associated with increased risk of AKI (adjusted odds ratio 1.30 [1.04-1.63], P = .02). Furthermore, in patients with postoperative AKI, those with baseline albuminuria had a worse prognosis with regard to 1-year mortality (adjusted hazard ratio 2.81 [1.56-5.09], P < .001) and persistent renal function impairment (adjusted odds ratio 2.07 [1.21-3.46], P = .007), independent of estimated glomerular filtration rate values. Patients with baseline hematuria and pyuria also had an inferior postoperative AKI prognosis when compared to those without the urinalysis abnormalities. Baseline dipstick urinalysis may predict postoperative AKI and may be significantly associated with prognosis after surgery. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.
Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia.
Goldstein, Felicia C; Steenland, Kyle; Zhao, Liping; Wharton, Whitney; Levey, Allan I; Hajjar, Ihab
2017-09-01
To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD). Observational, longitudinal study. Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging. Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists. Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66-0.93, P = .005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69-0.98, P = .03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76-0.93, P = .001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74-0.91, P = .001). This lower risk was found for persons with normal cognition or MCI. Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Willeit, Peter; Raschenberger, Julia; Heydon, Emma E; Tsimikas, Sotirios; Haun, Margot; Mayr, Agnes; Weger, Siegfried; Witztum, Joseph L; Butterworth, Adam S; Willeit, Johann; Kronenberg, Florian; Kiechl, Stefan
2014-01-01
Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies. Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis. Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I2 = 69%). Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.
Prognostic value of exercise pulmonary haemodynamics in pulmonary arterial hypertension.
Chaouat, Ari; Sitbon, Olivier; Mercy, Magalie; Ponçot-Mongars, Raphaëlle; Provencher, Steeve; Guillaumot, Anne; Gomez, Emmanuel; Selton-Suty, Christine; Malvestio, Pascale; Regent, Denis; Paris, Christophe; Hervé, Philippe; Chabot, François
2014-09-01
The aim of the study was to investigate the prognostic value of right heart catheterisation variables measured during exercise. 55 incident patients with idiopathic, familial or anorexigen-associated pulmonary arterial hypertension (PAH) underwent right heart catheterisation at rest and during exercise and 6-min walk testing before PAH treatment initiation. Patients were treated according to recommendations within the next 2 weeks. Right heart catheterisation was repeated 3-5 months into the PAH treatment in 20 patients. Exercise cardiac index decreased gradually as New York Heart Association (NYHA) functional class increased whereas cardiac index at rest was not significantly different across NYHA groups. Baseline 6-min walk distance correlated significantly with exercise and change in cardiac index from rest to exercise (r=0.414 and r=0.481, respectively; p<0.01). Change in 6-min walk distance from baseline to 3-5 months under PAH treatment was highly correlated with change in exercise cardiac index (r=0.746, p<0.001). The most significant baseline covariates associated with survival were change in systolic pulmonary artery pressure from rest to exercise and exercise cardiac index (hazard ratio 0.56 (95% CI 0.37-0.86) and 0.14 (95% CI 0.05-0.43), respectively). Change in pulmonary haemodynamics during exercise is an important tool for assessing disease severity and may help devise optimal treat-to-target strategies. ©ERS 2014.
Hazardous drinking and military community functioning: identifying mediating risk factors.
Foran, Heather M; Heyman, Richard E; Slep, Amy M Smith
2011-08-01
Hazardous drinking is a serious societal concern in military populations. Efforts to reduce hazardous drinking among military personnel have been limited in effectiveness. There is a need for a deeper understanding of how community-based prevention models apply to hazardous drinking in the military. Community-wide prevention efforts may be most effective in targeting community functioning (e.g., support from formal agencies, community cohesion) that impacts hazardous drinking via other proximal risk factors. The goal of the current study is to inform community-wide prevention efforts by testing a model of community functioning and mediating risk factors of hazardous drinking among active duty U.S. Air Force personnel. A large, representative survey sample of U.S. Air Force active duty members (N = 52,780) was collected at 82 bases worldwide. Hazardous drinking was assessed with the widely used Alcohol Use Disorders Identification Test (Saunders, Aasland, Babor, de la Fuente, & Grant, 1993). A variety of individual, family, and community measures were also assessed. Structural equation modeling was used to test a hypothesized model of community functioning, mediating risk factors and hazardous drinking. Depressive symptoms, perceived financial stress, and satisfaction with the U.S. Air Force were identified as significant mediators of the link between community functioning and hazardous drinking for men and women. Relationship satisfaction was also identified as a mediator for men. These results provide a framework for further community prevention research and suggest that prevention efforts geared at increasing aspects of community functioning (e.g., the U.S. Air Force Community Capacity model) may indirectly lead to reductions in hazardous drinking through other proximal risk factors.
2013-06-01
high-performance contact adhesive (baseline) can be used to bond most rubber, cloth, metal, wood , foamed glass, paper honeycomb, decorative plastic ...and gasket adhesive (baseline) may be used to bond metal, wood , most plastics , neoprene, SBR, and butyl rubber (11). Key features are high immediate...nitrile rubber, most plastics and gasketing materials to a variety of substrates (13). This product contains 0% HAPs (14) and has been added to the
Choudhary, Gaurav; Jankowich, Matthew; Wu, Wen-Chih
2014-07-01
Although elevated pulmonary artery systolic pressure (PASP) is associated with heart failure (HF), whether PASP measurement can help predict future HF admissions is not known, especially in African Americans who are at increased risk for HF. We hypothesized that elevated PASP is associated with increased risk of HF admission and improves HF prediction in African American population. We conducted a longitudinal analysis using the Jackson Heart Study cohort (n=3125; 32.2% men) with baseline echocardiography-derived PASP and follow-up for HF admissions. Hazard ratio for HF admission was estimated using Cox proportional hazard model adjusted for variables in the Atherosclerosis Risk in Community (ARIC) HF prediction model. During a median follow-up of 3.46 years, 3.42% of the cohort was admitted for HF. Subjects with HF had a higher PASP (35.6±11.4 versus 27.6±6.9 mm Hg; P<0.001). The hazard of HF admission increased with higher baseline PASP (adjusted hazard ratio per 10 mm Hg increase in PASP: 2.03; 95% confidence interval, 1.67-2.48; adjusted hazard ratio for highest [≥33 mm Hg] versus lowest quartile [<24 mm Hg] of PASP: 2.69; 95% confidence interval, 1.43-5.06) and remained significant irrespective of history of HF or preserved/reduced ejection fraction. Addition of PASP to the ARIC model resulted in a significant improvement in model discrimination (area under the curve=0.82 before versus 0.84 after; P=0.03) and improved net reclassification index (11-15%) using PASP as a continuous or dichotomous (cutoff=33 mm Hg) variable. Elevated PASP predicts HF admissions in African Americans and may aid in early identification of at-risk subjects for aggressive risk factor modification. © 2014 American Heart Association, Inc.
Circulating active serum calcium reduces the risk of hypertension.
Kunutsor, Setor K; Laukkanen, Jari A
2017-02-01
Purpose Calcium, which is one the most abundant mineral elements in the body, has been suggested to be involved in blood pressure regulation. We aimed to assess the association of active serum calcium (which is the ionised and physiologically active form of serum calcium) with the future risk of hypertension. Methods The active serum calcium concentration was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease population-based prospective cohort study of 1562 normotensive men aged 42-61 years at baseline. Cox proportional hazard models were used to assess the hazard ratios (95% confidence intervals (CIs)) for incident hypertension. Results During a median follow-up of 24.9 years, 247 men developed new-onset hypertension. Active serum calcium was inversely associated with incident hypertension in an approximately linear fashion. In age-adjusted analysis, the hazard ratio for hypertension per 1 standard deviation increase in active serum calcium was 0.86 (95% CI 0.76-0.98), which remained consistent after adjustment for several established risk factors and potential confounders 0.82 (0.71-0.94). In a comparison of extreme quintiles of active serum calcium levels, the corresponding adjusted hazard ratios were 0.59 (95% CI 0.39-0.90) and 0.54 (95% CI 0.35-0.82), respectively. Conclusion Active serum calcium is protective of future hypertension in a middle-aged male Caucasian population. Further research is needed to confirm these findings and help unravel the mechanistic pathways of calcium in the pathogenesis of hypertension.
Confidence intervals for the first crossing point of two hazard functions.
Cheng, Ming-Yen; Qiu, Peihua; Tan, Xianming; Tu, Dongsheng
2009-12-01
The phenomenon of crossing hazard rates is common in clinical trials with time to event endpoints. Many methods have been proposed for testing equality of hazard functions against a crossing hazards alternative. However, there has been relatively few approaches available in the literature for point or interval estimation of the crossing time point. The problem of constructing confidence intervals for the first crossing time point of two hazard functions is considered in this paper. After reviewing a recent procedure based on Cox proportional hazard modeling with Box-Cox transformation of the time to event, a nonparametric procedure using the kernel smoothing estimate of the hazard ratio is proposed. The proposed procedure and the one based on Cox proportional hazard modeling with Box-Cox transformation of the time to event are both evaluated by Monte-Carlo simulations and applied to two clinical trial datasets.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-19
... Compatibility Group S indicates that hazardous effects from accidental functioning are limited to the extent the... package is capable of containing any hazardous effects in the event of an accidental functioning of its... demonstrate that any hazardous effects are confined within a package. In the ANPRM, we invited commenters to...
Kunutsor, Setor Kwadzo; Whitehouse, Michael Richard; Blom, Ashley William; Laukkanen, Jari Antero
2017-07-01
Magnesium, which is an essential trace element that plays a key role in several cellular processes, is a major component of bone; however, its relationship with risk of major bone fractures is uncertain. We aimed to investigate the association of baseline serum magnesium concentrations with risk of incident fractures. We analyzed data on 2245 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study, with the assessment of serum magnesium measurements and dietary intakes made at baseline. Hazard ratios [95% confidence intervals (CI)] for incident total (femoral, humeral, and forearm) and femoral fractures were assessed. During a median follow-up of 25.6 years, 123 total fractures were recorded. Serum magnesium was non-linearly associated with risk of total fractures. In age-adjusted Cox regression analysis, the hazard ratio (HR) (95% CIs) for total fractures in a comparison of the bottom quartile versus top quartile of magnesium concentrations was 2.10 (1.30-3.41), which persisted on adjustment for several established risk factors 1.99 (1.23-3.24). The association remained consistent on further adjustment for renal function, socioeconomic status, total energy intake, and several trace elements 1.80 (1.10-2.94). The corresponding adjusted HRs for femoral fractures were 2.56 (1.38-4.76), 2.43 (1.30-4.53) and 2.13 (1.13-3.99) respectively. There was no evidence of an association of dietary magnesium intake with risk of any fractures. In middle-aged Caucasian men, low serum magnesium is strongly and independently associated with an increased risk of fractures. Further research is needed to assess the potential relevance of serum magnesium in the prevention of fractures.
Camargo, Antonio; Jimenez-Lucena, Rosa; Alcala-Diaz, Juan F; Rangel-Zuñiga, Oriol A; Garcia-Carpintero, Sonia; Lopez-Moreno, Javier; Blanco-Rojo, Ruth; Delgado-Lista, Javier; Perez-Martinez, Pablo; van Ommen, Ben; Malagon, Maria M; Ordovas, Jose M; Perez-Jimenez, Francisco; Lopez-Miranda, Jose
2018-04-11
Insulin resistance (IR) and impaired beta-cell function are key determinants of type 2 diabetes mellitus (T2DM). Intestinal absorption of bacterial components activates the toll-like receptors inducing inflammation, and this in turn IR. We evaluated the role of endotoxemia in promoting inflammation-induced insulin resistance (IR) in the development of T2DM, and its usefulness as predictive biomarker. We included in this study 462 patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months (Incident-DIAB group), whereas 355 patients did not developed it during this period of time (Non-DIAB group). We observed a postprandial increase in lipopolysaccharides (LPS) levels in the Incident-DIAB at baseline (P < 0.001), whereas LPS levels were not modified in the Non-DIAB. Disease-free survival curves based on the LPS postprandial fold change improved T2DM Risk Assessment as compared with the previously described FINDRISC score (hazard ratio of 2.076, 95% CI 1.149-3.750 vs. 1.384, 95% CI 0.740-2.589). Moreover, disease-free survival curves combining the LPS postprandial fold change and FINDRISC score together showed a hazard ratio of 3.835 (95% CI 1.323-11.114), linked to high values of both parameters. Our results suggest that a high postprandial endotoxemia precedes the development of T2DM. Our results also showed the potential use of LPS plasma levels as a biomarker predictor of T2DM development. CLINICAL TRIALS.GOV. NCT00924937. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Deo, Rajat; Katz, Ronit; Shlipak, Michael G.; Sotoodehnia, Nona; Psaty, Bruce M.; Sarnak, Mark J.; Fried, Linda F.; Chonchol, Michel; de Boer, Ian H.; Enquobahrie, Daniel; Siscovick, David; Kestenbaum, Bryan
2012-01-01
Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2,312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations: 2 events per 10,000 for 25-OHD ≥ 20 ng/ml and 4 events per 10,000 for 25-OHD < 20 ng/ml. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations: 2 events per 10,000 for PTH ≤ 65 pg/ml and 4 events per 10,000 for PTH > 65 pg/ml. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a more than 2-fold risk of SCD after adjustment (hazard ratio 2.19, 95% confidence interval 1.17, 4.10, p=0.017) compared to participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. PMID:22068871
Stroke Symptoms as a Predictor of Future Hospitalization.
Howard, Virginia J; Safford, Monika M; Allen, Shauntice; Judd, Suzanne E; Rhodes, J David; Kleindorfer, Dawn O; Soliman, Elsayed Z; Meschia, James F; Howard, George
2016-03-01
Stroke symptoms in the general adult population are common and associated with stroke risk factors, lower physical and mental functioning, impaired cognitive status, and future stroke. Our objective was to determine the association of stroke symptoms with self-reported hospitalization or emergency department (ED) visit. Lifetime history of stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, loss of ability to communicate or understand) was assessed at baseline in a national, population-based, longitudinal cohort study of 30,239 blacks and whites younger than 45 years, enrolled from 2003 to 2007. Self-reported hospitalization or ED visit and reason were collected during follow-up through March 2013. The symptom-hospitalization association was assessed by proportional hazards analysis in persons who were stroke/transient ischemic attack-free at baseline (27,126) with adjustment for sociodemographics and further adjustment for risk factors. One or more stroke symptoms were reported by 4758 (17.5%). After adjustment for sociodemographics, stroke symptoms were most strongly associated with greater risk of hospitalization/ED for cardiovascular disease (CVD) (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.78-1.96), stroke (HR = 1.69, 95% CI: 1.55-1.85), and any reason (HR = 1.39, 95% CI: 1.34-1.44). These associations remained significant and only modestly reduced after risk factor adjustment. Stroke symptoms are a marker for future hospitalization and ED visit not only for stroke but also for CVD in general. Findings suggest a role for stroke symptom assessment as a novel and simple approach for identifying individuals at high risk for CVD including stroke in whom preventive strategies could be implemented. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Lindsay, Alistair C; Harron, Katie; Jabbour, Richard J; Kanyal, Ritesh; Snow, Thomas M; Sawhney, Paramvir; Alpendurada, Francisco; Roughton, Michael; Pennell, Dudley J; Duncan, Alison; Di Mario, Carlo; Davies, Simon W; Mohiaddin, Raad H; Moat, Neil E
2016-07-01
Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation. © 2016 American Heart Association, Inc.
Proof of Principle for Electronic Collimation of a Gamma Ray Detector
2016-01-01
complete the Environmental Baseline Survey mission for soldiers. The monitoring of radioactive waste handling, as well as other sources of radioactive ...electronic collimation of a gamma ray spectroscopic detector will include identifying and characterizing environmentally hazardous radioactivity to
49 CFR 192.919 - What must be in the baseline assessment plan?
Code of Federal Regulations, 2010 CFR
2010-10-01
....919 Section 192.919 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM FEDERAL SAFETY STANDARDS Gas...
Menotti, Alessandro; Puddu, Paolo Emilio; Maiani, Giuseppe; Catasta, Giovina
2016-05-01
To relate major causes of death with lifestyle habits in an almost extinct male middle-aged population. A 40-59 aged male population of 1712 subjects was examined and followed-up for 50 years. Baseline smoking habits, working physical activity and dietary habits were related to 50 years mortality subdivided into 12 simple and 3 composite causes of death by Cox proportional hazard models. Duration of survival was related to the same characteristics by a multiple linear regression model. Death rate in 50 years was of 97.5%. Out of 12 simple groups of causes of death, 6 were related to smoking habits, 3 to physical activity and 4 to dietary habits. Among composite groups of causes of death, hazard ratios (and their 95% confidence limits) of never smokers versus smokers were 0.68 (0.57-0.81) for major cardiovascular diseases; 0.65 (0.52-0.81) for all cancers; and 0.72 (0.64-0.81) for all-cause deaths. Hazard ratios of vigorous physical activity at work versus sedentary physical activity were 0.63 (0.49-0.80) for major cardiovascular diseases; 1.01 (0.72-1.41) for all cancers; and 0.76 (0.64-0.90) for all-cause deaths. Hazard ratios of Mediterranean Diet versus non-Mediterranean Diet were 0.68 (0.54-0.86) for major cardiovascular diseases; 0.54 (0.40-0.73) for all cancers; and 0.67 (0.57-0.78) for all-cause deaths. Expectancy of life was 12 years longer for men with the 3 best behaviors than for those with the 3 worst behaviors. Some lifestyle habits are strongly related to lifetime mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis.
Shah, R C; Buchman, A S; Wilson, R S; Leurgans, S E; Bennett, D A
2011-07-19
To test the hypothesis that level of hemoglobin is associated with incident Alzheimer disease (AD). A total of 881 community-dwelling older persons participating in the Rush Memory and Aging Project without dementia and a measure of hemoglobin level underwent annual cognitive assessments and clinical evaluations for AD. During an average of 3.3 years of follow-up, 113 persons developed AD. In a Cox proportional hazards model adjusted for age, sex, and education, there was a nonlinear relationship between baseline level of hemoglobin such that higher and lower levels of hemoglobin were associated with AD risk (hazard ratio [HR] for the quadratic of hemoglobin 1.06, 95% confidence interval [CI] 1.01-1.11). Findings were unchanged after controlling for multiple covariates. When compared to participants with clinically normal hemoglobin (n = 717), participants with anemia (n = 154) had a 60% increased hazard for developing AD (95% CI 1.02-2.52), as did participants with clinically high hemoglobin (n = 10, HR 3.39, 95% CI 1.25-9.20). Linear mixed-effects models showed that lower and higher hemoglobin levels were associated with a greater rate of global cognitive decline (parameter estimate for quadratic of hemoglobin = -0.008, SE -0.002, p < 0.001). Compared to participants with clinically normal hemoglobin, participants with anemia had a -0.061 z score unit annual decline in global cognitive function (SE 0.012, p < 0.001), as did participants with clinically high hemoglobin (-0.090 unit/year, SE 0.038, p = 0.018). In older persons without dementia, both lower and higher hemoglobin levels are associated with an increased hazard for developing AD and more rapid cognitive decline.
Synopsis of Precision Landing and Hazard Avoidance (PL&HA) Capabilities for Space Exploration
NASA Technical Reports Server (NTRS)
Robertson, Edward A.
2017-01-01
Until recently, robotic exploration missions to the Moon, Mars, and other solar system bodies relied upon controlled blind landings. Because terrestrial techniques for terrain relative navigation (TRN) had not yet been evolved to support space exploration, landing dispersions were driven by the capabilities of inertial navigation systems combined with surface relative altimetry and velocimetry. Lacking tight control over the actual landing location, mission success depended on the statistical vetting of candidate landing areas within the predicted landing dispersion ellipse based on orbital reconnaissance data, combined with the ability of the spacecraft to execute a controlled landing in terms of touchdown attitude, attitude rates, and velocity. In addition, the sensors, algorithms, and processing technologies required to perform autonomous hazard detection and avoidance in real time during the landing sequence were not yet available. Over the past decade, NASA has invested substantial resources on the development, integration, and testing of autonomous precision landing and hazard avoidance (PL&HA) capabilities. In addition to substantially improving landing accuracy and safety, these autonomous PL&HA functions also offer access to targets of interest located within more rugged and hazardous terrain. Optical TRN systems are baselined on upcoming robotic landing missions to the Moon and Mars, and NASA JPL is investigating the development of a comprehensive PL&HA system for a Europa lander. These robotic missions will demonstrate and mature PL&HA technologies that are considered essential for future human exploration missions. PL&HA technologies also have applications to rendezvous and docking/berthing with other spacecraft, as well as proximity navigation, contact, and retrieval missions to smaller bodies with microgravity environments, such as asteroids.
Hemoglobin level in older persons and incident Alzheimer disease
Buchman, A.S.; Wilson, R.S.; Leurgans, S.E.; Bennett, D.A.
2011-01-01
Objective: To test the hypothesis that level of hemoglobin is associated with incident Alzheimer disease (AD). Methods: A total of 881 community-dwelling older persons participating in the Rush Memory and Aging Project without dementia and a measure of hemoglobin level underwent annual cognitive assessments and clinical evaluations for AD. Results: During an average of 3.3 years of follow-up, 113 persons developed AD. In a Cox proportional hazards model adjusted for age, sex, and education, there was a nonlinear relationship between baseline level of hemoglobin such that higher and lower levels of hemoglobin were associated with AD risk (hazard ratio [HR] for the quadratic of hemoglobin 1.06, 95% confidence interval [CI] 1.01–1.11). Findings were unchanged after controlling for multiple covariates. When compared to participants with clinically normal hemoglobin (n = 717), participants with anemia (n = 154) had a 60% increased hazard for developing AD (95% CI 1.02–2.52), as did participants with clinically high hemoglobin (n = 10, HR 3.39, 95% CI 1.25–9.20). Linear mixed-effects models showed that lower and higher hemoglobin levels were associated with a greater rate of global cognitive decline (parameter estimate for quadratic of hemoglobin = −0.008, SE −0.002, p < 0.001). Compared to participants with clinically normal hemoglobin, participants with anemia had a −0.061 z score unit annual decline in global cognitive function (SE 0.012, p < 0.001), as did participants with clinically high hemoglobin (−0.090 unit/year, SE 0.038, p = 0.018). Conclusions: In older persons without dementia, both lower and higher hemoglobin levels are associated with an increased hazard for developing AD and more rapid cognitive decline. PMID:21753176
Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young
2017-08-01
The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [ P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion: 18 F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Marihuana use. Biologic and behavioral aspects.
Mendelson, J H
1976-11-01
More than 70 male chronic marihuana users were studied under research ward conditions for a 31-day period consisting of 5 days of baseline assessment, 21 days of marihuana availability, and 5 days of postsmoking assessment. Biological findings were for the most part within normal limits. Blood chemistry studies showed no abnormalities. Plasma testosterone levels for all subjects at all times during the study were well within normal limits, suggesting that previous reports of testosterone suppression by marihuana may have statistical but not biologic singificance. A significant reduction in baseline vital capacity was observed in six subjects, a compromise in pulmonary function similar to that characteristically produced by chronic inhalation of substances, such as tobacco smoke, which are irritants to the lung. Increased caloric intake and weight gain occurred in virtually all subjects and were causally related to marihuana smoking. The weight gain may be attributable to water retention as well as increased caloric intake. Behavioral findings indicated that no uniform alteration in mood is produced by marihuana smoking--all subjects reported becoming "high", but experienced no consistent degree of euphoria. Mood changes which occurred were relatively mild and were largely dependent on group determinants rather than individual experience. No relationship could be established between marihuana use and motivation to work or engage in socially desirable activities. Evidence that pulmonary function may be compromised as a function of marihuana smoking suggests the need for alerting individuals to this potential health hazard. As was true of cigarette smoking, the eventual public health consequences of marihuana use may become apparent only after large numbers of individuals have smoked marihuana for two or three decades.
Wedderburn, Catherine J; van Beijnum, Janneke; Bhattacharya, Jo J; Counsell, Carl E; Papanastassiou, Vakis; Ritchie, Vaughn; Roberts, Richard C; Sellar, Robin J; Warlow, Charles P; Al-Shahi Salman, Rustam
2008-03-01
The decision about whether to treat an unruptured brain arteriovenous malformation (AVM) depends on a comparison of the estimated lifetime risk of intracranial haemorrhage with the risks of interventional treatment. We aimed to test whether outcome differs between adults who had interventional AVM treatment and those who did not. All adults in Scotland who were first diagnosed with an unruptured AVM during 1999-2003 (n=114) entered our prospective, population-based study. We compared the baseline characteristics and 3-year outcome of adults who received interventional treatment for their AVM (n=63) with those who did not (n=51). At presentation, adults who were treated were younger (mean 40 vs 55 years of age, 95% CI for difference 9-20; p<0.0001), more likely to present with a seizure (odds ratio 2.4, 95% CI 1.1-5.0), and had fewer comorbidities (median 3 vs 4, p=0.03) than those who were not treated. Despite these baseline imbalances, treated and untreated groups did not differ in progression to Oxford Handicap Scale (OHS) scores of 2-6 (log-rank p=0.12) or 3-6 (log-rank p=0.98) in survival analyses. In a multivariable Cox proportional hazards analysis, the risk of poor outcome (OHS 2-6) was greater in patients who had interventional treatment than in those who did not (hazard ratio 2.5, 95% CI 1.1-6.0) and was greater in patients with a larger AVM nidus (hazard ratio 1.3, 95% CI 1.1-1.7). The treated and untreated groups did not differ in time to an OHS score of 2 or more that was sustained until the end of the third year of follow-up, or in the spectrum of dependence as measured by the OHS at 1, 2, and 3 years of follow-up. Greater AVM size and interventional treatment were associated with worse short-term functional outcome for unruptured AVMs, but the longer-term effects of intervention are unclear.
Liu, J J; Lim, S C; Yeoh, L Y; Su, C; Tai, B C; Low, S; Fun, S; Tavintharan, S; Chia, K S; Tai, E S; Sum, C F
2016-03-01
To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.
Tea Consumption and Mortality Among Oldest-Old Chinese
Ruan, Rongping; Feng, Lei; Li, Jialiang; Ng, Tze-Pin; Zeng, Yi
2013-01-01
Objectives To investigate the association between tea consumption and mortality among oldest-old Chinese. Design Population-based longitudinal data from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) was analyzed using Cox semi-parametric proportional hazard model. Setting 631 randomly selected counties and cities of China’s 22 provinces. Participants 9,093 old adults aged 80 and above who provided complete data at baseline survey (year 1998). Measurements Self-reported current frequency of tea drinking and past frequency around age 60 were ascertained at baseline survey, and follow-up survey was conducted respectively in years 2000, 2002 and 2005. Results Among oldest-old Chinese, tea consumption was associated with reduced risk of mortality after adjusting for demographic characteristics, socioeconomic status, health practices, and health status. Compared with non-tea drinkers, the adjusted hazard ratio (HR) was 0.90 (95% CI 0.84–0.96) for daily tea drinkers (at the baseline survey, 1998) and 1.00 (95% CI 1.01–1.07) for occasional tea drinkers respectively (P for linear trend=0.003). Similar results were found when tea drinking status around age 60 was used in analysis. Further analysis showed that compared to consistently infrequent tea drinkers, subjects who reported frequent tea drinking at both age 60 and at baseline survey had a 10% reduction in mortality (HR=0.90, 95%CI 0.84–0.97). Conclusion Tea consumption is associated reduced risk of mortality among oldest-old Chinese. PMID:24117374
Lagro, Joep; Schoon, Yvonne; Heerts, Inger; Meel-van den Abeelen, Aisha S S; Schalk, Bianca; Wieling, Wouter; Olde Rikkert, Marcel G M; Claassen, Jurgen A H R
2014-04-01
Normally, standing up causes a blood pressure (BP) drop within 15 seconds, followed by recovery to baseline driven by BP control mechanisms. The prognostic value of this initial BP drop, but also of the recovery hereafter, is unknown. The aim of this study was to examine the prognostic value of these BP characteristics in response to standing. In a retrospective cohort study of 238 consecutive patients visiting our falls outpatient clinic, we examined the relation between all-cause mortality and BP decline and recovery directly after active standing up with Cox proportional hazards analyses. Of 238 patients (mean age 78.4 ± 7.8 years), during a median follow-up of 21.0 months, 36 (15%) patients died. Neither absolute nor relative (%) initial BP drop after standing predicted mortality. In contrast, the magnitude of BP recovery 40-60 seconds after standing was associated with mortality, even after adjustment for age, comorbidity, and other baseline characteristics. When systolic BP had recovered to less than 80% of prestanding baseline after 60 seconds of standing, this was a powerful independent predictor of mortality (hazard ratio: 3.00; 95% confidence interval 1.17-7.68). Failure to recover from BP decline in the first minute after active standing up is associated with excess mortality in falls clinic patients. A recovery of systolic BP to less than 80% of baseline after 60 seconds may be used as an easily available cardiovascular marker for increased mortality risk in older falls clinic patients.
Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min
2008-12-09
Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.
Choi, Sunha H
2012-04-01
This study tested a healthy immigrant effect (HIE) and postimmigration health status changes among late life immigrants. Using three waves of the Second Longitudinal Study of Aging (1994-2000) and the linked mortality file through 2006, this study compared (a) chronic health conditions, (b) longitudinal trajectories of self-rated health, (c) longitudinal trajectories of functional impairments, and (d) mortality between three groups (age 70+): (i) late life immigrants with less than 15 years in the United States (n = 133), (ii) longer term immigrants (n = 672), and (iii) U.S.-born individuals (n = 8,642). Logistic and Poisson regression, hierarchical generalized linear modeling, and survival analyses were conducted. Late life immigrants were less likely to suffer from cancer, had lower numbers of chronic conditions at baseline, and displayed lower hazards of mortality during the 12-year follow-up. However, their self-rated health and functional status were worse than those of their counterparts over time. A HIE was only partially supported among older adults.
Hulsegge, Gerben; Smit, Henriëtte A; van der Schouw, Yvonne T; Daviglus, Martha L; Verschuren, W M Monique
2015-10-01
Studies investigating the relation between risk profiles and cardiovascular disease have measured risk at baseline only. We investigated maintenance and changes of risk profiles over time and their potential impact on incident cardiovascular disease. Population-based cohort study. Risk factors were measured at baseline (1987-1991) among 5574 cardiovascular disease-free adults aged 20-59 years. They were classified into four risk categories according to smoking status, presence of diabetes and widely accepted cut-off values for blood pressure, total cholesterol/HDL-ratio and body mass index. Categories were subdivided (maintenance, deterioration, improvement) based on risk factor levels at six and 11 years of follow-up. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular disease incidence 5-10 years following the risk-change period were fitted using Cox proportional hazards models. Only 12% of participants were low risk at baseline, and only 7% maintained it. Participants who maintained a low risk profile over 11 years had seven times lower risk of cardiovascular disease (HR: 0.14, 95% CI: 0.05-0.41) than participants with long-term high risk profile, whereas those low risk at baseline whose profile deteriorated had three times lower risk (HR: 0.36, 95% CI: 0.18-0.71). Our results suggest that, within each baseline risk profile group, compared with a stable profile, improving profiles may be associated with up to two-fold lower HRs, and deteriorating profiles with about two-fold higher HRs. Our study, using long-term risk profiles, demonstrates the full benefits of low risk profile. These findings underscore the importance of achieving and maintaining low risk from young adulthood onwards. © The European Society of Cardiology 2014.
Imamura, Kotaro; Kawakami, Norito; Inoue, Akiomi; Shimazu, Akihito; Tsutsumi, Akizumi; Takahashi, Masaya; Totsuzaki, Takafumi
2016-01-01
This study investigated work engagement as a baseline predictor of onset of major depressive episode (MDE). The study used a prospective cohort design, conforming to the STROBE checklist. Participants were recruited from the employee population of a private think tank company (N = 4,270), and 1,058 (24.8%) of them completed a baseline survey, of whom 929 were included in this study. Work engagement and psychological distress at baseline were assessed as predictor variables. MDE was measured at baseline and at each of the follow-ups as the outcome, using the web-based, self-administered version of the Japanese WHO-CIDI 3.0 depression section based upon DSM-IV-TR/DSM-5 criteria. Cox discrete-time hazards analyses were conducted to estimate hazard ratios (95% confidence intervals CIs). Follow-up rates of participants (N = 929) were 78.4%, 67.2%, and 51.6% at 1-, 2-, and 3-year follow-ups, respectively. The association between work engagement at baseline and the onset of MDE was U-shaped. Compared with a group with low work engagement scores, groups with the middle and high scores showed significantly (HR = 0.19, 95% CI = 0.05 to 0.64; p = 0.007) and marginally significantly (HR = 0.48, 95% CI = 0.20 to 1.15, p = 0.099) lower risks of MDE, respectively, over the follow-ups, after adjusting for covariates. The pattern remained the same after additionally adjusting for psychological distress. The present study first demonstrated work engagement as an important predictor of the onset of MDE diagnosed according to an internationally standard diagnostic criteria of mental disorders.
Norton, Joanna; Portet, Florence; Gabelle, Audrey; Debette, Stephanie; Ritchie, Karen; Touchon, Jacques; Berr, Claudine
2016-01-01
Background There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non-migrainous headache (NMH) has received little attention as a potential risk factor, despite being the most frequently reported type of headache. Late-life migraine and NMH were examined as candidate risk factors for stroke in a community-dwelling elderly sample over a 12-year follow-up. Methods 1919 non-institutionalized subjects 65+, without dementia (DSM-IV criteria) and no stroke history at baseline were drawn from the 3C-Montpellier cohort (recruitment 1999–2001) for the longitudinal analysis. Ischemic and haemorrhagic stroke was reported at baseline, and at each of the 5 follow-ups, with ICD-10 cases validated by a panel of experts. Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 IHS criteria. Results 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8 year follow-up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke, however NMH sufferers were twice as likely to have a stroke (Hazard Ratio=2.00, 95% CI: 1.00–3.93, p=0.049). Conclusions This study is one of the first to suggest that late-life NMH rather than migraine could be an independent risk factor for stroke and warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low. PMID:27399611
Imamura, Kotaro; Kawakami, Norito; Inoue, Akiomi; Shimazu, Akihito; Tsutsumi, Akizumi; Takahashi, Masaya; Totsuzaki, Takafumi
2016-01-01
Objective This study investigated work engagement as a baseline predictor of onset of major depressive episode (MDE). Methods The study used a prospective cohort design, conforming to the STROBE checklist. Participants were recruited from the employee population of a private think tank company (N = 4,270), and 1,058 (24.8%) of them completed a baseline survey, of whom 929 were included in this study. Work engagement and psychological distress at baseline were assessed as predictor variables. MDE was measured at baseline and at each of the follow-ups as the outcome, using the web-based, self-administered version of the Japanese WHO-CIDI 3.0 depression section based upon DSM-IV-TR/DSM-5 criteria. Cox discrete-time hazards analyses were conducted to estimate hazard ratios (95% confidence intervals CIs). Results Follow-up rates of participants (N = 929) were 78.4%, 67.2%, and 51.6% at 1-, 2-, and 3-year follow-ups, respectively. The association between work engagement at baseline and the onset of MDE was U-shaped. Compared with a group with low work engagement scores, groups with the middle and high scores showed significantly (HR = 0.19, 95% CI = 0.05 to 0.64; p = 0.007) and marginally significantly (HR = 0.48, 95% CI = 0.20 to 1.15, p = 0.099) lower risks of MDE, respectively, over the follow-ups, after adjusting for covariates. The pattern remained the same after additionally adjusting for psychological distress. Conclusions The present study first demonstrated work engagement as an important predictor of the onset of MDE diagnosed according to an internationally standard diagnostic criteria of mental disorders. PMID:26841020
Quality assurance audits of medical surveillance programs for hazardous waste workers.
Udasin, I G; Buckler, G; Gochfeld, M
1991-11-01
The Occupational Safety and Health Administration (OSHA) Hazardous Waste Operations and Emergency Response Regulation (29 CFR 1910.120) requires medical surveillance examinations for hazardous waste workers. We investigated the consistency and appropriateness of the services provided under OSHA 29 CFR 1910.120 as part of a quality control audit. Our study revealed that in most cases the required paperwork including fitness for duty and restrictions or limitations was completed. However, it is also apparent that many of the components of a complete occupational history were not performed. Spirometric examinations often were performed incorrectly. Documentation of baseline tests was not uniformly done, nor were patients always informed of the findings of their examinations. Our study indicated there may be a lack of education, training, and experience of occupational health providers. This suggests that further efforts should be made to educate physicians and nurses providing medical surveillance and other services to hazardous waste workers.
Kadoglou, Nikolaos Pe; Mandila, Christina; Karavidas, Apostolos; Farmakis, Dimitrios; Matzaraki, Vasiliki; Varounis, Christos; Arapi, Sofia; Perpinia, Anastasia; Parissis, John
2017-05-01
Background/design Functional electrical stimulation of lower limb muscles is an alternative method of training in patients with chronic heart failure (CHF). Although it improves exercise capacity in CHF, we performed a randomised, placebo-controlled study to investigate its effects on long-term clinical outcomes. Methods We randomly assigned 120 patients, aged 71 ± 8 years, with stable CHF (New York Heart Association (NYHA) class II/III (63%/37%), mean left ventricular ejection fraction 28 ± 5%), to either a 6-week functional electrical stimulation training programme or placebo. Patients were followed for up to 19 months for death and/or hospitalisation due to CHF decompensation. Results At baseline, there were no significant differences in demographic parameters, CHF severity and medications between groups. During a median follow-up of 383 days, 14 patients died (11 cardiac, three non-cardiac deaths), while 40 patients were hospitalised for CHF decompensation. Mortality did not differ between groups (log rank test P = 0.680), while the heart failure-related hospitalisation rate was significantly lower in the functional electrical stimulation group (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.21-0.78, P = 0.007). The latter difference remained significant after adjustment for prognostic factors: age, gender, baseline NYHA class and left ventricular ejection fraction (HR 0.22, 95% CI 0.10-0.46, P < 0.001). Compared to placebo, functional electrical stimulation training was associated with a lower occurrence of the composite endpoint (death or heart failure-related hospitalisation) after adjustment for the above-mentioned prognostic factors (HR 0.21, 95% CI 0.103-0.435, P < 0.001). However, that effect was mostly driven by the favourable change in hospitalisation rates. Conclusions In CHF patients, 6 weeks functional electrical stimulation training reduced the risk of heart failure-related hospitalisations, without affecting the mortality rate. The beneficial long-term effects of this alternative method of training require further investigation.
NASA Astrophysics Data System (ADS)
Zhao, Chao-ying; Zhang, Qin; Yang, Chengsheng; Zou, Weibao
2011-07-01
Datong is located in the north of Shanxi Province, which is famous for its old-fashioned coal-mining preservation in China. Some serious issues such as land subsidence, ground fissures, mining collapse, and earthquake hazards have occurred over this area for a long time resulting in significant damages to buildings and roads. In order to monitor and mitigate these natural man-made hazards, Short Baseline Subsets (SBAS) InSAR technique with ten Envisat ASAR data is applied to detect the surface deformation over an area of thousands of square kilometers. Then, five MODIS data are used to check the atmospheric effects on InSAR interferograms. Finally, nine nonlinear land subsidence cumulative results during September 2004 and February 2008 are obtained. Based on the deformation data, three kinds of land subsidence are clearly detected, caused by mine extraction, underground water withdrawal and construction of new economic zones, respectively. The annual mean velocity of subsidence can reach 1 to 4 cm/year in different subsidence areas. A newly designed high-speed railway (HSR) with speeds of 350 km/h will cross through the Datong hi-tech zone. Special measures should be taken for the long run of this project. In addition, another two subsidence regions need further investigation to mitigate such hazards.
Choi, Mun Hee; Yoon, Jung Han; Yong, Suk Woo
2017-10-15
Postganglionic cardiac sympathetic denervation is evident in patients with early-stage Parkinson's disease (PD). Cardiac iodine-123-meta-iodobenzylguanidine (MIBG) uptake is correlated with the non-motor symptoms of PD, suggesting that low cardiac MIBG uptake may reflect wider alpha-synuclein pathology. In addition, low cardiac MIBG could be related to orthostatic hypotension in PD, which may affect cognition. However, the prognostic validity of baseline MIBG scintigraphy in terms of the risk of subsequent dementia remains unclear. We investigated whether cardiac MIBG uptake was associated with a later risk of dementia. We retrospectively enrolled 93 drug-naive patients with de novo PD who underwent MIBG scanning on initial evaluation. The patients visited our outpatient clinic every 3-6months and were followed-up for a minimum of 4years from the time they were begun on dopaminergic medication. The predictive powers of baseline MIBG cardiac scintigraphic data in terms of dementia development were evaluated using Cox's proportional hazard models. During a mean follow-up period of 6.7years, 27 patients with PD (29.0%) developed dementia. These patients had less baseline MIBG uptake than did others (delayed H/M ratios: 1.19 vs. 1.31). Multivariate Cox's proportional hazard modeling revealed that both MIBG uptake (hazard ratio [HR] 3.40; p=0.004) and age (HR 1.08, p=0.01) significantly predicted dementia development. A reduction in cardiac MIBG uptake by PD patients may be associated with a subsequent risk of dementia; reduced uptake may reflect wider extension of alpha-synuclein pathology in PD. Copyright © 2017 Elsevier B.V. All rights reserved.
Pascual, Jose Maria; Rodilla, Enrique; Gonzalez, Carmen; Pérez-Hoyos, Santiago; Redon, Josep
2005-06-01
The objective was to assess the temporal impact of factors related to the development of microalbuminuria during the follow-up of young adult normoalbuminurics with high-normal blood pressure or at stage 1 of essential hypertension. Prospective follow-up was conducted on 245 normoalbuminuric hypertensive subjects (mean age 40.9 years; 134 men; blood pressure 139.7/88.6 mm Hg; body mass index 28.5 kg/m2) never treated previously with antihypertensive drugs, with yearly urinary albumin excretion measurements, until the development of microalbuminuria. After enrollment, patients were placed on usual care including nonpharmacological treatment or with an antihypertensive drug regime to achieve a blood pressure of <135/85 mm Hg. Thirty subjects (12.2%) developed microalbuminuria after a mean follow-up of 29.9 months (range 12 to 144 months), 2.5 per 100 patients per year. Baseline urinary albumin excretion (hazard ratio, 1.07; P=0.006) and systolic blood pressure during the follow-up (hazard ratio, 1.03; P=0.008) were independent factors related to the follow-up urinary albumin excretion in a Cox proportional hazard model. A significant increase in the risk of developing microalbuminuria for urinary albumin excretion at baseline >15 mg per 24-hour systolic blood pressure >139 mm Hg and a positive trend in fasting glucose were observed in the univariate analyses. However, in the multivariate analysis, only the baseline urinary albumin excretion and the trend of fasting glucose were independently related to the risk of developing microalbuminuria. In mild hypertensives, the development of microalbuminuria was linked to insufficient blood pressure control and to a progressive increment of glucose values.
Heikkilä, Katriina; Madsen, Ida E. H.; Nyberg, Solja T.; Fransson, Eleonor I.; Ahola, Kirsi; Alfredsson, Lars; Bjorner, Jakob B.; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Ferrie, Jane E.; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Nielsen, Martin L.; Nordin, Maria; Pejtersen, Jan H.; Pentti, Jaana; Rugulies, Reiner; Oksanen, Tuula; Shipley, Martin J.; Suominen, Sakari B.; Theorell, Töres; Väänänen, Ari; Vahtera, Jussi; Virtanen, Marianna; Westerlund, Hugo; Westerholm, Peter J. M.; Batty, G. David; Singh-Manoux, Archana; Kivimäki, Mika
2014-01-01
Background and Aims Many clinicians, patients and patient advocacy groups believe stress to have a causal role in inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. However, this is not corroborated by clear epidemiological research evidence. We investigated the association between work-related stress and incident Crohn's disease and ulcerative colitis using individual-level data from 95 000 European adults. Methods We conducted individual-participant data meta-analyses in a set of pooled data from 11 prospective European studies. All studies are a part of the IPD-Work Consortium. Work-related psychosocial stress was operationalised as job strain (a combination of high demands and low control at work) and was self-reported at baseline. Crohn's disease and ulcerative colitis were ascertained from national hospitalisation and drug reimbursement registers. The associations between job strain and inflammatory bowel disease outcomes were modelled using Cox proportional hazards regression. The study-specific results were combined in random effects meta-analyses. Results Of the 95 379 participants who were free of inflammatory bowel disease at baseline, 111 men and women developed Crohn's disease and 414 developed ulcerative colitis during follow-up. Job strain at baseline was not associated with incident Crohn's disease (multivariable-adjusted random effects hazard ratio: 0.83, 95% confidence interval: 0.48, 1.43) or ulcerative colitis (hazard ratio: 1.06, 95% CI: 0.76, 1.48). There was negligible heterogeneity among the study-specific associations. Conclusions Our findings suggest that job strain, an indicator of work-related stress, is not a major risk factor for Crohn's disease or ulcerative colitis. PMID:24558416
Loss to Follow-Up in a Community Clinic in South Africa – Roles of Gender, Pregnancy and CD4 count
Wang, Bingxia; Losina, Elena; Stark, Ruth; Munro, Alison; Walensky, Rochelle P.; Wilke, Marisa; Martin, Des; Lu, Zhigang; Freedberg, Kenneth A.; Wood, Robin
2013-01-01
Background Faith-based organizations have expanded access to antiretroviral therapy (ART) in community clinics across South Africa. Loss to follow-up (LTFU), however, limits both the potential individual and population treatment benefits and is an obstacle to optimal care. Objective To identify patient characteristics associated with LTFU six months after starting ART in patients in a large South African community clinic. Methods Patients initiating ART between April 2004 and October 2006 in one Catholic Relief Services HIV treatment clinic who had at least one follow-up visit were included in the analysis. Standardized instruments were used for data collection. Routine monitoring was performed every 6 months following ART initiation. Rates of LTFU over time were estimated by the Kaplan-Meier method. The log-rank test was used to examine the impact of age, baseline CD4 count, HIV RNA, gender and pregnancy status for women on LTFU. Cox proportional hazard regression was performed to analyze hazard ratios for LTFU. Results Data from 925 patients (age > 14 years), median age 36 years, 70% female (16% pregnant) were included in the analysis. Fifty one patients (6%) were lost to follow-up six months after ART initiation. When stratified by baseline CD4 count, gender and pregnancy status, pregnant women with lower baseline CD4 count (≤200 /μl) had 6.06 times (95% CI: 2.20 – 16.71) the hazard of LTFU compared to men. Conclusions HIV-infected pregnant women initiating ART are significantly more likely to be lost to follow-up in a community clinic in South Africa. Interventions to successfully retain pregnant women in care are urgently needed. PMID:21786730
Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan; Lee, Hyun Moo; Cho, Seong Whi
2014-05-01
The purpose of this study is to retrospectively investigate whether pretreatment multiparametric MRI findings can predict biochemical recurrence in patients who underwent radical prostatectomy (RP) for localized prostate cancer. In this study, 282 patients with biopsy-proven prostate cancer who received RP underwent pretreatment MRI using a phased-array coil at 3 T, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI). MRI variables included apparent tumor presence on combined imaging sequences, extracapsular extension, and tumor size on DWI or DCE-MRI. Clinical variables included baseline prostate-specific antigen (PSA) level, clinical stage, and Gleason score at biopsy. The relationship between clinical and imaging variables and biochemical recurrence was evaluated using Cox regression analysis. After a median follow-up of 26 months, biochemical recurrence developed in 61 patients (22%). Univariate analysis revealed that all the imaging and clinical variables were significantly associated with biochemical recurrence (p < 0.01). On multivariate analysis, however, baseline PSA level (p = 0.002), Gleason score at biopsy (p = 0.024), and apparent tumor presence on combined T2WI, DWI, and DCE-MRI (p = 0.047) were the only significant independent predictors of biochemical recurrence. Of the independent predictors, apparent tumor presence on combined T2WI, DWI, and DCE-MRI showed the highest hazard ratio (2.38) compared with baseline PSA level (hazard ratio, 1.05) and Gleason score at biopsy (hazard ratio, 1.34). The apparent tumor presence on combined T2WI, DWI, and DCE-MRI of pretreatment MRI is an independent predictor of biochemical recurrence after RP. This finding may be used to construct a predictive model for biochemical recurrence after surgery.
Postural changes in blood pressure and incidence of ischemic stroke subtypes: the ARIC study.
Yatsuya, Hiroshi; Folsom, Aaron R; Alonso, Alvaro; Gottesman, Rebecca F; Rose, Kathryn M
2011-02-01
The relation of orthostatic blood pressure decrease, or increase, with occurrence of ischemic stroke subtypes has not been examined. We investigated the association of orthostatic blood pressure change (within 2 minutes after supine to standing) obtained at baseline (1987 to 1989) in the Atherosclerosis Risk in Communities Study with incidence of ischemic stroke subtypes through 2007. Among 12 817 black and white individuals without a history of stroke at baseline, 680 ischemic strokes (153 lacunar, 383 nonlacunar thrombotic, and 144 cardioembolic strokes) occurred during a median follow-up of 18.7 years. There was a U-shaped association between orthostatic systolic blood pressure change and lacunar stroke incidence (quadratic P=0.004). In contrast, orthostatic systolic blood pressure decrease of 20 mm Hg or more was associated with increased occurrence of nonlacunar thrombotic and cardioembolic strokes independent of sitting systolic blood pressure, antihypertensive medication use, diabetes, and other lifestyle, physiological, biochemical, and medical conditions at baseline (for nonlacunar thrombotic: hazard ratio, 2.02; 95% CI, 1.43 to 2.84; for cardioembolic: hazard ratio, 1.85, 95% CI, 1.01 to 3.39). Orthostatic diastolic blood pressure decrease was associated with increased risk of nonlacunar thrombotic and cardioembolic strokes; the hazard ratios (95% CI) associated with 10 mm Hg lower orthostatic diastolic blood pressure (continuous) were 1.26 (1.06 to 1.50) and 1.41 (1.06 to 1.88), respectively, in fully adjusted models. In conclusion, the present study found that nonlacunar ischemic stroke incidence was positively associated with an orthostatic decrease of systolic and diastolic blood pressure, whereas greater lacunar stroke incidence was associated with both orthostatic increases and decreases in systolic blood pressure.
Gordon-Dseagu, Vanessa L Z; Thompson, Frances E; Subar, Amy F; Ruder, Elizabeth H; Thiébaut, Anne C M; Potischman, Nancy; Stolzenberg-Solomon, Rachael
2017-08-01
Given the long latency period of pancreatic cancer, exploring the influence of early and midlife exposures will further advance our understanding of the disease. We assessed associations between diet and pancreatic cancer incidence in the National Institutes of Health (NIH)-AARP (formerly American Association of Retired Persons) Diet and Health Study. In 1996, a total of 303,094 participants completed 2 food frequency questionnaires that assessed diet at ages 12-13 years and 10 years previously. We used Cox proportional hazards regression to estimate adjusted hazard ratios and 95% confidence intervals. Through the end of 2006, a total of 1,322 pancreatic cancer cases occurred (average follow up time = 10.1 years). When comparing the highest tertiles with the lowest, carbohydrate intake during adolescence (hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.76, 0.99), but not 10 years before baseline, was inversely associated with pancreatic cancer risk. Total fat intake 10 years before baseline was significantly associated with increased risk (HR = 1.17, 95% CI: 1.02, 1.34), while risk was higher for high fat intake during both adolescence and midlife. Calcium intake 10 years before baseline was associated with reduced risk (HR = 0.87, 95% CI: 0.76, 0.99), as was a change from low intake in adolescence to high intake in midlife (HR = 0.71, 95% CI: 0.54, 0.93). Our study found a number of dietary factors present during adolescence and midlife to be associated with pancreatic cancer. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Tracking Temporal Hazard in the Human Electroencephalogram Using a Forward Encoding Model
2018-01-01
Abstract Human observers automatically extract temporal contingencies from the environment and predict the onset of future events. Temporal predictions are modeled by the hazard function, which describes the instantaneous probability for an event to occur given it has not occurred yet. Here, we tackle the question of whether and how the human brain tracks continuous temporal hazard on a moment-to-moment basis, and how flexibly it adjusts to strictly implicit variations in the hazard function. We applied an encoding-model approach to human electroencephalographic data recorded during a pitch-discrimination task, in which we implicitly manipulated temporal predictability of the target tones by varying the interval between cue and target tone (i.e. the foreperiod). Critically, temporal predictability either was driven solely by the passage of time (resulting in a monotonic hazard function) or was modulated to increase at intermediate foreperiods (resulting in a modulated hazard function with a peak at the intermediate foreperiod). Forward-encoding models trained to predict the recorded EEG signal from different temporal hazard functions were able to distinguish between experimental conditions, showing that implicit variations of temporal hazard bear tractable signatures in the human electroencephalogram. Notably, this tracking signal was reconstructed best from the supplementary motor area, underlining this area’s link to cognitive processing of time. Our results underline the relevance of temporal hazard to cognitive processing and show that the predictive accuracy of the encoding-model approach can be utilized to track abstract time-resolved stimuli. PMID:29740594
2011-01-01
Introduction Long-term outcomes of elderly patients after medical ICU care are little known. The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU. Methods We prospectively studied 112/230 healthy elderly patients (≥65 years surviving at least 12 months after ICU discharge) with full functional autonomy without cognitive impairment prior to ICU entry. The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III (APACHE III) classification diagnosis and length of ICU stay and ICU scores (APACHE II, Sepsis-related Organ Failure Assessment (SOFA) and OMEGA) at admission and discharge were collected. Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton, Barthel, and Charlson Indexes and Informant Questionnaire on Cognitive Decline to evaluate functionality, comorbidity and cognitive status, respectively. The EuroQol-5D assessed quality of life. Data were collected at baseline, during ICU and ward stay and 3, 6 and 12 months after hospital discharge. Paired or unpaired T-tests compared differences between groups (continuous variables), whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables. For variables significant (P ≤ 0.1) on univariate analysis, a forward multiple regression analysis was performed. Results Only 48.9% of patients (mean age: 73.4 ± 5.5 years) were alive 12 months after discharge showing a significant decrease in functional autonomy (Lawton and Barthel Indexes) and quality of life (EuroQol-5D) compared to baseline status (P < 0.001, all). Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery (P < 0.01, both). Thus, in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥40 at discharge the hazard ratio for full functional recovery was 4.04 (95% CI: 1.58 to 10.33; P = 0.005) and 6.1 (95% CI: 1.9 to 19.9; P < 0.01), respectively. Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up (P < 0.001). Conclusions The survival rate of elderly medical patients 12 months after discharge from the ICU is low (49%), although functional status and quality of life remained similar to baseline in most of the survivors. However, there was a two-fold increase in the prevalence of geriatric syndromes. PMID:21443796
[Hazard function and life table: an introduction to the failure time analysis].
Matsushita, K; Inaba, H
1987-04-01
Failure time analysis has become popular in demographic studies. It can be viewed as a part of regression analysis with limited dependent variables as well as a special case of event history analysis and multistate demography. The idea of hazard function and failure time analysis, however, has not been properly introduced to nor commonly discussed by demographers in Japan. The concept of hazard function in comparison with life tables is briefly described, where the force of mortality is interchangeable with the hazard rate. The basic idea of failure time analysis is summarized for the cases of exponential distribution, normal distribution, and proportional hazard models. The multiple decrement life table is also introduced as an example of lifetime data analysis with cause-specific hazard rates.
Graubard, Barry I.
2018-01-01
Restaurant prepared foods are known to be energy-dense and high in fat and sodium, but lower in protective nutrients. There is evidence of higher risk of adiposity, type II diabetes, and heart disease in frequent consumers of restaurant meals. However, the risk of mortality as a long-term health consequence of frequent consumption of restaurant meals has not been examined. We examined the prospective risk of all-cause and coronary heart disease, cerebrovascular disease and diabetes (cardiometabolic) mortality in relation to frequency of eating restaurant prepared meals in a national cohort. We used frequency of eating restaurant prepared meals information collected in the National Health and Nutrition Examination Surveys, conducted from 1999–2004, with mortality follow-up completed through Dec. 31, 2011 (baseline age ≥ 40y; n = 9107). We estimated the relative hazard of all-cause and cardiometabolic mortality associated with weekly frequency of eating restaurant meals using Cox-proportional hazards regression methods to adjust for multiple covariates. All analyses accounted for complex survey design and included sample weights. Over 33% of all respondents reported eating ≥3 restaurant prepared meals/week. In this cohort, 2200 deaths due to all causes and 665 cardiometabolic deaths occurred over a median follow-up of 9 years. The covariate-adjusted hazard ratio of all cause or cardiometabolic mortality in men and women reporters of <1 or 1–2 restaurant prepared meals did not differ from those reporting ≥3 meals/week (P>0.05). The results were robust to effect modification by baseline BMI, years of education, and baseline morbidity. Expectedly, the 24-h dietary intakes of whole grains, fruits, dietary fiber, folate, vitamin C, potassium and magnesium at baseline were lower, but energy, energy density, and energy from fat were higher in more frequent restaurant meal reporters (P<0.05). Baseline serum HDL cholesterol, folate, and some carotenoids were inversely associated with the frequency of eating restaurant prepared meals (P<0.05); however, serum concentrations of total cholesterol, triglycerides, fasting glucose, insulin, glycated hemoglobin, and c-reactive protein were unrelated (P<0.05). The weekly frequency of eating restaurant prepared meals and prospective risk of mortality after 9 years were not related in this cohort. PMID:29360850
Kant, Ashima K; Graubard, Barry I
2018-01-01
Restaurant prepared foods are known to be energy-dense and high in fat and sodium, but lower in protective nutrients. There is evidence of higher risk of adiposity, type II diabetes, and heart disease in frequent consumers of restaurant meals. However, the risk of mortality as a long-term health consequence of frequent consumption of restaurant meals has not been examined. We examined the prospective risk of all-cause and coronary heart disease, cerebrovascular disease and diabetes (cardiometabolic) mortality in relation to frequency of eating restaurant prepared meals in a national cohort. We used frequency of eating restaurant prepared meals information collected in the National Health and Nutrition Examination Surveys, conducted from 1999-2004, with mortality follow-up completed through Dec. 31, 2011 (baseline age ≥ 40y; n = 9107). We estimated the relative hazard of all-cause and cardiometabolic mortality associated with weekly frequency of eating restaurant meals using Cox-proportional hazards regression methods to adjust for multiple covariates. All analyses accounted for complex survey design and included sample weights. Over 33% of all respondents reported eating ≥3 restaurant prepared meals/week. In this cohort, 2200 deaths due to all causes and 665 cardiometabolic deaths occurred over a median follow-up of 9 years. The covariate-adjusted hazard ratio of all cause or cardiometabolic mortality in men and women reporters of <1 or 1-2 restaurant prepared meals did not differ from those reporting ≥3 meals/week (P>0.05). The results were robust to effect modification by baseline BMI, years of education, and baseline morbidity. Expectedly, the 24-h dietary intakes of whole grains, fruits, dietary fiber, folate, vitamin C, potassium and magnesium at baseline were lower, but energy, energy density, and energy from fat were higher in more frequent restaurant meal reporters (P<0.05). Baseline serum HDL cholesterol, folate, and some carotenoids were inversely associated with the frequency of eating restaurant prepared meals (P<0.05); however, serum concentrations of total cholesterol, triglycerides, fasting glucose, insulin, glycated hemoglobin, and c-reactive protein were unrelated (P<0.05). The weekly frequency of eating restaurant prepared meals and prospective risk of mortality after 9 years were not related in this cohort.
Zimering, Mark B.; Anderson, Robert J.; Ge, Ling; Moritz, Thomas E.; Duckworth, William C.
2013-01-01
Aim: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in adults with type 2 diabetes mellitus. The aim of the present study was to test whether plasma basic fibroblast growth factor (bFGF) levels predict future CVD occurrence in adults from the Veterans Affairs Diabetes Trial (VADT). Methods: Nearly 400 veterans, 40 years of age or older having a mean baseline diabetes duration of 11.4 years were recruited from outpatient clinics at six geographically distributed sites in the VADT. Within the VADT, they were randomly assigned to intensive or standard glycemic treatment, with follow-up as much as seven and one-half years. CVD occurrence was examined at baseline in the patient population and during randomized treatment. Plasma bFGF was determined with a sensitive, specific two-site enzyme-linked immunoassay at the baseline study visit in all 399 subjects and repeated at the year 1 study visit in a randomly selected subset of 215 subjects. Results: One hundred and five first cardiovascular events occurred in these 399 subjects. The best fit model of risk factors associated with the time to first CVD occurrence (in the study) over a seven and one-half year period had as significant predictors: prior cardiovascular event [hazard ratio (HR) 3.378; 95% confidence intervals (CI) 3.079–3.807; P < 0.0001), baseline plasma bFGF (HR 1.008; 95% CI 1.002–1.014; P = 0.01), age (HR 1.027; 95% CI 1.004–1.051; P = 0.019), baseline plasma triglycerides (HR 1.001; 95% CI 1.000–1.002; P = 0.02), and diabetes duration-treatment interaction (P = 0.03). Intensive glucose-lowering was associated with significantly decreased hazard ratios for CVD occurrence (0.38–0.63) in patients with known diabetes duration of 0–10 years, and non-significantly increased hazard ratios for CVD occurrence (0.82–1.78) in patients with longer diabetes duration. Conclusion: High level of plasma bFGF is a predictive biomarker of future CVD occurrence in this population of adult type 2 diabetes. PMID:24319441
2012-01-01
Background Based on findings primarily using self-report measures, physical activity has been recommended to reduce disability in old age. Collecting objective measures of total daily physical activity in community-dwelling older adults is uncommon, but might enhance the understanding of the relationship of physical activity and disability. We examined whether greater total daily physical activity was associated with less report of disability in the elderly. Methods Data were from the Rush Memory and Aging Project, a longitudinal prospective cohort study of common, age-related, chronic conditions. Total daily physical activity was measured in community-dwelling participants with an average age of 82 using actigraphy for approximately 9 days. Disability was measured via self-reported basic activities of daily living (ADL). The odds ratio and 95% Confidence Interval (CI) were determined for the baseline association of total daily physical activity and ADL disability using a logistic regression model adjusted for age, education level, gender and self-report physical activity. In participants without initial report of ADL disability, the hazard ratio and 95% CI were determined for the relationship of baseline total daily physical activity and the development of ADL disability using a discrete time Cox proportional hazard model adjusted for demographics and self-report physical activity. Results In 870 participants, the mean total daily physical activity was 2. 9 × 105 counts/day (range in 105 counts/day = 0.16, 13. 6) and the mean hours/week of self-reported physical activity was 3.2 (SD = 3.6). At baseline, 718 (82.5%) participants reported being independent in all ADLs. At baseline, total daily physical activity was protective against disability (OR per 105 counts/day difference = 0.55; 95% CI = 0.47, 0.65). Of the participants without baseline disability, 584 were followed for 3.4 years on average. Each 105 counts/day additional total daily physical activity was associated with reduced hazard of developing disability by 25% (HR = 0.75, 95% CI = 0.66, 0.84). The results were unchanged after controlling for important covariates including cognition, depressive symptoms, and chronic health conditions. Conclusions Greater total daily physical activity is independently associated with less disability even after controlling for self-reported physical activity. PMID:23072476
Patel, U B; Brown, G; Machado, I; Santos-Cores, J; Pericay, C; Ballesteros, E; Salud, A; Isabel-Gil, M; Montagut, C; Maurel, J; Ramón-Ayuso, J; Martin, N; Estevan, R; Fernandez-Martos, C
2017-02-01
Primary chemotherapy has been tested as a possible approach for patients with high risk features but predicted clear mesorectal margins on preoperative MRI assessment. This study investigates the prognostic relevance of baseline and post-treatment MRI and pathology staging in rectal cancer patients undergoing primary chemotherapy. Forty-six patients with T3 tumour > =2 mm from the mesorectal fascia were prospectively treated with Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between 2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour regression grade (TRG) and modified-RECIST assessment of tumour length. The post-treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were also recorded. Three-year disease-free survival (DFS) and cumulative incidence of recurrence were estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging and response on MRI and pathology with survival outcomes. About 46 patients underwent neoadjuvant chemotherapy alone for high risk margin safe primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11 patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46 patients were identified with MRI features of EMVI at baseline. mrEMVI positive status carried independent prognostic significance for DFS (P = 0.0097) with a hazard ratio of 31.33 (95% CI: 2.3-425.4). The histopathologic factor that was of independent prognostic importance was a final ypT downstage of ypT3a or less, hazard ratio: 14.0 (95% CI: 1.5-132.5). mrEMVI is an independent prognostic factor at baseline for poor outcomes in rectal cancer treated with neoadjuvant chemotherapy while ≤ypT3a is associated with an improvement in DFS. Future preoperative therapy evaluation in rectal cancer patients will need to stratify treatment according to baseline EMVI status as a crucial risk factor for recurrence in patients with predicted CRM clear rectal cancer. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Sleep problems and disability retirement: a register-based follow-up study.
Lallukka, Tea; Haaramo, Peija; Lahelma, Eero; Rahkonen, Ossi
2011-04-15
Among aging employees, sleep problems are prevalent, but they may have serious consequences that are poorly understood. This study examined whether sleep problems are associated with subsequent disability retirement. Baseline questionnaire survey data collected in 2000-2002 among employees of the city of Helsinki, Finland, were linked with register data on disability retirement diagnoses by the end of 2008 (n = 457) for those with written consent for such linkages (74%; N = 5,986). Sleep problems were measured by the Jenkins Sleep Questionnaire. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals for disability retirement. Gender- and age-adjusted frequent sleep problems predicted disability retirement due to all causes (hazard ratio (HR) = 3.22, 95% confidence interval (CI): 2.26, 4.60), mental disorders (HR = 9.06, 95% CI: 3.27, 25.10), and musculoskeletal disorders (HR = 3.27, 95% CI: 1.91, 5.61). Adjustments for confounders, that is, baseline sociodemographic factors, work arrangements, psychosocial working conditions, and sleep duration, had negligible effects on these associations, whereas baseline physical working conditions and health attenuated the associations. Health behaviors and obesity did not mediate the examined associations. In conclusion, sleep problems are associated with subsequent disability retirement. To prevent early exit from work, sleep problems among aging employees need to be addressed.
Theis, K A; Roblin, D; Helmick, C G; Luo, R
2018-05-28
Negative employment consequences of arthritis are known but not fully understood. Examining transitions in and out of work can provide valuable information. To examine associations of arthritis with employment during the Great Recession and predictors of employment transitions. Data were for 3,277 adults ages 30-62 years with and without arthritis from the 2007 National Health Interview Survey followed in the Medical Expenditure Panel Survey 2008-2009. Employment (working vs. not working) was ascertained at baseline and five follow-ups. We estimated Kaplan Meier survival curves with 95% confidence intervals (CI) separately for time to stopping work (working at baseline) and starting work (not working at baseline) using Cox proportional hazards regression models with hazard ratios (HR). Arthritis was significantly associated with greater risk of stopping work (HR = 1.7, 95% CI = 1.3-2.2; adjusted HR= 1.5, 95% CI = 1.1-2.0) and significantly associated with 40% lower chance of starting work (HR = 0.6, 95% CI = 0.4-0.8); which reversed on adjustment (HR = 1.5, 95% CI = 1.0-2.2). Employment predictors were mixed by outcome. During the Great Recession, adults with arthritis stopped work at higher rates and started work at lower rates than those without arthritis.
Brenowitz, Willa D.; Kukull, Walter A.; Beresford, Shirley A. A.; Monsell, Sarah E.; Williams, Emily C.
2014-01-01
Social relationships are hypothesized to prevent or slow cognitive decline. We sought to evaluate associations between social relationships and mild cognitive impairment (MCI). Participants from the National Alzheimer’s Coordinating Center database who were cognitively normal, aged 55 and older at baseline, and had at least two in-person visits (n=5,335) were included. Multivariable Cox proportional hazard models evaluated the association between four social relationships at baseline (marital status, living situation, having children, and having siblings) and risk of developing MCI (based on clinician diagnosis following established criteria). Primary models were adjusted for baseline demographics. Participants were followed, on average, for 3.2 years; 15.2% were diagnosed with MCI. Compared to married participants, risk of MCI was significantly lower for widowed participants (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.76, 0.99) but not for divorced/separated or never married participants. Compared to living with a spouse/partner, risk of MCI was significantly higher for living with others (HR: 1.35; 95% CI: 1.03, 1.77) but not for living alone. Risk of MCI was not associated with having children or having siblings. These results did not consistently identify social relationships as a strong risk factor for, or independent clinical predictor of, MCI. PMID:24577205
Letang, Emilio; Lewis, James J; Bower, Mark; Mosam, Anisa; Borok, Margareth; Campbell, Thomas B; Naniche, Denise; Newsom-Davis, Tom; Shaik, Fahmida; Fiorillo, Suzanne; Miro, Jose M; Schellenberg, David; Easterbrook, Philippa J
2013-06-19
To assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral therapy (ART)-naive HIV-infected patients with Kaposi sarcoma initiating ART in both well resourced and limited-resourced settings. Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with Kaposi sarcoma from sub-Saharan Africa (SSA) and one from the UK. KS-IRIS case definition was standardized across sites. Cox regression and Kaplan-Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and Kaposi sarcoma-associated mortality. Fifty-eight of 417 (13.9%) eligible individuals experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (P=0.001). ART alone as initial Kaposi sarcoma treatment (hazard ratio 2.97, 95% confidence interval (CI) 1.02-8.69); T1 Kaposi sarcoma stage (hazard ratio 2.96, 95% CI 1.26-6.94); and plasma HIV-1 RNA more than 5 log₁₀ copies/ml (hazard ratio 2.14, 95% CI 1.25-3.67) independently predicted KS-IRIS at baseline. Detectable plasma Kaposi sarcoma-associated herpes virus (KSHV) DNA additionally predicted KS-IRIS among the 259 patients with KSHV DNA assessed (hazard ratio 2.98, 95% CI 1.23-7.19). Nineteen KS-IRIS patients died, all in SSA. Kaposi sarcoma mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (hazard ratio 19.24, CI 7.62-48.58), lack of chemotherapy (hazard ratio 2.35, 95% CI 1.09-5.05), pre-ART CD4 cell count less than 200 cells/μl (hazard ratio 2.04, 95% CI 0.99-4.2), and detectable baseline KSHV DNA (hazard ratio 2.12, 95% CI 0.94-4.77). KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced Kaposi sarcoma disease and lower chemotherapy availability. KS-IRIS is a major contributor to Kaposi sarcoma-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of Kaposi sarcoma, and advocate on access to systemic chemotherapy in Africa. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins
An Analysis of Contraceptive Discontinuation among Female, Reversible Method Users in Urban Honduras
Barden-O’Fallon, Janine; Speizer, Ilene S.; Cálix, Javier; Rodriguez, Francisco
2013-01-01
A panel study examining the effects of individual characteristics, side effects experienced, and service quality on contraceptive discontinuation was undertaken in four urban areas of Honduras. Data were collected from October 2006 to December 2007. The baseline population included 800 women aged 15–44 who were new or continuing users of the injectable, IUD, or oral contraceptive pill. A total of 671 women (84%) were re-interviewed after one year. Life tables and Cox proportional hazards models are used to present discontinuation rates and factors associated with contraceptive discontinuation. Among new users, discontinuation of the baseline method at 12 months was high (45%); especially for users of the injectable (50%). In the hazards model, service quality had little effect on discontinuation, while individual characteristics and the experience of specific side effects showed significant effects. The results suggest that programs should emphasize continuous contraceptive coverage rather than continuous use of a particular method. PMID:21500697
Copertaro, A; Bracci, M; Amati, Monica; Mocchegiani, E; Barbaresi, Mariella; Copertaro, Benedetta; Santarelli, Lory
2010-01-01
Healthcare workers may be exposed to a variety of biological hazards. Although many studies have shown that some immunological alterations were related to work stress and sleep disorders, few studies investigated effects of shiftwork on the immunological system. The aim of the study was to compare the immune status of a group of nurses on shiftwork with that of nurses working only day shifts. A total of 138 nurses were evaluated at baseline and after a year of follow-up, via tests for perceived stress, daytime sleepiness, number of lymphocytes and subpopulation of CD3+, CD4+, CD8+-CD57+, CD19+ and CD56+, cytotoxic activity and lympho-prolferative response of NK cells, serum concentrations of IL-1beta, IL-6, INFgamma and TNFalpha. No significant alterations of any of the studied parameters were found both at baseline and after a year of follow-up. The biological hazards for nurses do not seem to be increased by shiftwork.
Calcium and Vitamin D Supplementation and Cognitive Impairment in the Women’s Health Initiative
Rossom, Rebecca C.; Espeland, Mark A.; Manson, JoAnn E.; Dysken, Maurice W.; Johnson, Karen C.; Lane, Dorothy S.; LeBlanc, Erin S.; Lederle, Frank A.; Masaki, Kamal H.; Margolis, Karen L.
2012-01-01
Background Calcium and vitamin D are thought to play important roles in neuronal functioning. Studies have found associations between low serum vitamin D levels and reduced cognitive functioning, as well as high serum calcium levels and reduced cognitive functioning. Objectives To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. Design Post-hoc analysis of a randomized double-blinded placebo-controlled trial. Setting 40 Women’s Health Initiative clinical centers across the U.S. Participants 4143 women aged 65 years and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D trial and the Women’s Health Initiative Memory Study. Interventions 2034 women were randomized to 1000 mg of calcium carbonate combined with 400 IU of vitamin D3; 2109 women were randomized to placebo. Measurements Primary: classifications of probable dementia or mild cognitive impairment via a 4-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. Results Mean age of participants was 71 years. During mean follow-up of 7.8 years, there were 39 cases of incident dementia among calcium plus vitamin D subjects compared to 37 cases among placebo subjects (hazard ratio=1.11, 95% CI: 0.71–1.74, p=0.64). Likewise, there were 98 cases of incident mild cognitive impairment among calcium plus vitamin D subjects compared to 108 cases among placebo subjects (hazard ratio=0.95, 95% CI: 0.72–1.25, p=0.72). There were no significant differences in incident dementia or mild cognitive impairment, or in global or domain-specific cognitive function between groups. Conclusion There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men and in other age and ethnic groups, and with other doses. PMID:23176129
Huisingh, Carrie; McGwin, Gerald; Owsley, Cynthia
2017-01-01
Background Many studies on vision and driving cessation have relied on measures of sensory function, which are insensitive to the higher order cognitive aspects of visual processing. The purpose of this study was to examine the association between traditional measures of visual sensory function and higher order visual processing skills with incident driving cessation in a population-based sample of older drivers. Methods Two thousand licensed drivers aged ≥70 were enrolled and followed-up for three years. Tests for central vision and visual processing were administered at baseline and included visual acuity, contrast sensitivity, sensitivity in the driving visual field, visual processing speed (Useful Field of View (UFOV) Subtest 2 and Trails B), and spatial ability measured by the Visual Closure Subtest of the Motor-free Visual Perception Test. Participants self-reported the month and year of driving cessation and provided a reason for cessation. Cox proportional hazards models were used to generate crude and adjusted hazard ratios with 95% confidence intervals between visual functioning characteristics and risk of driving cessation over a three-year period. Results During the study period, 164 participants stopped driving which corresponds to a cumulative incidence of 8.5%. Impaired contrast sensitivity, visual fields, visual processing speed (UFOVand Trails B), and spatial ability were significant risk factors for subsequent driving cessation after adjusting for age, gender, marital status, number of medical conditions, and miles driven. Visual acuity impairment was not associated with driving cessation. Medical problems (63%), specifically musculoskeletal and neurological problems, as well as vision problems (17%) were cited most frequently as the reason for driving cessation. Conclusion Assessment of cognitive and visual functioning can provide useful information about subsequent risk of driving cessation among older drivers. In addition, a variety of factors, not just vision, influenced the decision to stop driving and may be amenable to intervention. PMID:27353969
Troy, Jesse D.; Hartge, Patricia; Weissfeld, Joel L.; Oken, Martin M.; Colditz, Graham A.; Mechanic, Leah E.; Morton, Lindsay M.
2010-01-01
Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all; e.g., for baseline BMI ≥30 vs. 18.5–24.9, hazard ratio = 1.32, 95% confidence interval: 1.13, 1.54). Smoking was not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never: hazard ratio = 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week: Ptrend = 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do not support a causal association between alcohol and NHL. PMID:20494998
Hazard Function Estimation with Cause-of-Death Data Missing at Random.
Wang, Qihua; Dinse, Gregg E; Liu, Chunling
2012-04-01
Hazard function estimation is an important part of survival analysis. Interest often centers on estimating the hazard function associated with a particular cause of death. We propose three nonparametric kernel estimators for the hazard function, all of which are appropriate when death times are subject to random censorship and censoring indicators can be missing at random. Specifically, we present a regression surrogate estimator, an imputation estimator, and an inverse probability weighted estimator. All three estimators are uniformly strongly consistent and asymptotically normal. We derive asymptotic representations of the mean squared error and the mean integrated squared error for these estimators and we discuss a data-driven bandwidth selection method. A simulation study, conducted to assess finite sample behavior, demonstrates that the proposed hazard estimators perform relatively well. We illustrate our methods with an analysis of some vascular disease data.
Topp, Max S; Zimmerman, Zachary; Cannell, Paul; Dombret, Hervé; Maertens, Johan; Stein, Anthony; Franklin, Janet; Tran, Qui; Cong, Ze; Schuh, Andre C
2018-05-08
In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 post-baseline result were available in any EORTC multi-item scale or single-item measure. In general, patients receiving blinatumomab (n=247) reported better posttreatment HRQL across all QLQ-C30 subscales, based on descriptive mean change from baseline, than did those receiving chemotherapy (n=95). The hazard ratios for time to a ≥10-point deterioration from baseline (TTD) in HRQL or death ranged from 0.42 to 0.81 in favor of blinatumomab, with the upper bounds of the 95% CI <1.0 across all measures, except insomnia, social functioning, and financial difficulties; sensitivity analysis of TTD in HRQL without the event of death were consistent with these findings. When treatment effect over time was tested using a restricted maximum likelihood-based mixed model for repeated measures analysis, p<0.05 was reached for blinatumomab vs chemotherapy for all subscale measures except financial difficulties. The clinically meaningful benefits in overall survival and HRQL support the clinical value of blinatumomab in patients with R/R Ph- BCP-ALL when compared with chemotherapy. Funded by Amgen (TOWER ClinicalTrials.gov number, NCT02013167). Copyright © 2018 American Society of Hematology.
Biegstraaten, Marieke; Hughes, Derralynn A.; Mehta, Atul; Elliott, Perry M.; Oder, Daniel; Watkinson, Oliver T.; Vaz, Frédéric M.; van Kuilenburg, André B. P.; Wanner, Christoph; Hollak, Carla E. M.
2017-01-01
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension. PMID:28763515
Tsutsumimoto, Kota; Makizako, Hyuma; Doi, Takehiko; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Shimada, Hiroyuki; Suzuki, Takao
2017-06-01
Although subjective memory complaints (SMCs) are considered a risk factor for incident dementia in older people, the effect might differ based on cognitive function. The aim of the present study was to investigate whether the effect of SMCs on the incidence of dementia in older people differed based on cognitive function. A 24-month follow-up cohort study. Japanese community. Prospective, longitudinal data for incident dementia were collected for 3,672 participants (mean age: 71.7 years; 46.5% men) for up to 24 months. Baseline measurements included covariates for incident dementia, SMCs, and cognitive function. Associations between SMCs, cognitive impairment, and incident dementia were examined using Cox proportional hazards models. Incidences of dementia in the cognitively intact without SMC, cognitively intact with SMC, cognitive impairment without SMC, and cognitive impairment with SMC groups were 0.3%, 1.8%, 3.4%, and 4.8%, respectively. In the cognitively intact participants, SMCs were associated with a significantly higher risk of dementia (hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 1.52-16.11, p = 0.008). Incident dementia with cognitive impairment was not significantly different based on SMC presence (p = 0.527). Participants with cognitive impairment in multiple domains had a significantly higher risk of incident dementia (HR: 2.07, 95% CI: 1.01-4.24, p = 0.046) CONCLUSION: SMCs were related with dementia in cognitively intact older people, but not in those with cognitive impairment.Multiple domains of cognitive impairment were associated with a higher risk of incident dementia. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
30 CFR 585.645 - What must I include in my GAP?
Code of Federal Regulations, 2013 CFR
2013-07-01
...) You must provide the following results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data... geotechnical survey with supporting data A description of all relevant seabed and engineering data and...
30 CFR 585.645 - What must I include in my GAP?
Code of Federal Regulations, 2012 CFR
2012-07-01
...) You must provide the following results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data... geotechnical survey with supporting data A description of all relevant seabed and engineering data and...
30 CFR 585.610 - What must I include in my SAP?
Code of Federal Regulations, 2013 CFR
2013-07-01
... offshore and onshore. (6) General structural and project design, fabrication, and installation Information... requested by BOEM. (b) You must provide the results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data...
30 CFR 585.610 - What must I include in my SAP?
Code of Federal Regulations, 2014 CFR
2014-07-01
... offshore and onshore. (6) General structural and project design, fabrication, and installation Information... requested by BOEM. (b) You must provide the results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data...
30 CFR 585.645 - What must I include in my GAP?
Code of Federal Regulations, 2014 CFR
2014-07-01
...) You must provide the following results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data... geotechnical survey with supporting data A description of all relevant seabed and engineering data and...
30 CFR 585.610 - What must I include in my SAP?
Code of Federal Regulations, 2012 CFR
2012-07-01
... offshore and onshore. (6) General structural and project design, fabrication, and installation Information... requested by BOEM. (b) You must provide the results of geophysical and geological surveys, hazards surveys, archaeological surveys (if required), and baseline collection studies (e.g., biological) with the supporting data...
Kaplan, Mark S.; Huguet, Nathalie; Feeny, David; McFarland, Bentson H.; Caetano, Raul; Bernier, Julie; Giesbrecht, Norman; Oliver, Lisa; Ramage-Morin, Pamela; Ross, Nancy A.
2013-01-01
Studies have shown that moderate alcohol use confers protection against some of the dominant predictors of long-term care placement, including diminished cognitive functioning, physical disability, and injury. But little is known about the association between alcohol use and the likelihood of placement in long-term care facilities. A nationally representative sample of 5,404 community-dwelling Canadians ages 50 years and older at baseline (1994/95) was obtained from the longitudinal National Population Health Survey. Alcohol use categories were developed based on the quantity and frequency of use in the 12 months before the interview. Cox proportional hazards models were used to estimate the association between alcohol use at baseline and subsequent placement in long-term care facilities after adjusting for covariates measured at baseline. During the 14-year follow-up period, 14% of lifetime abstainers, 10% of former drinkers, 7% of infrequent drinkers, 4% of moderate drinkers, and 3% of heavy drinkers were placed in long-term care facilities. Furthermore, the multivariate analysis revealed that abstainers, former drinkers, and infrequent drinkers were more than twice as likely to be placed in long-term care as moderate drinkers. Moderate drinking was protective against placement in long-term care facilities even after adjusting for an array of well-known confounders. The strong protective effect of moderate alcohol use on long-term care entry is likely due to a complex mix of physical, cognitive and psychosocial health factors. PMID:24169370
Serum magnesium and risk of new onset heart failure in men: the Kuopio Ischemic Heart Disease Study.
Kunutsor, Setor K; Khan, Hassan; Laukkanen, Jari A
2016-10-01
Serum magnesium is an essential intracellular cation involved in processes that regulate cardiovascular function and has been linked to the risk of several cardiovascular disease outcomes. We aimed to investigate the association of serum magnesium concentrations with risk of incident heart failure (HF). We studied 2181 middle-aged men without prevalent HF (aged 42-61 years) enrolled in the finnish Kuopio Ischemic Heart Disease prospective cohort study with serum magnesium measurements made at baseline. Hazard ratios (95 % confidence intervals [CI]) for HF were assessed. During a median follow-up of 24.8 years, 278 HF events occurred. Baseline serum magnesium was weakly and inversely associated with several clinical markers and was continuously associated with risk of HF. The age-adjusted HR (95 % CIs) for HF per 1 standard deviation (SD) higher serum magnesium levels was 0.86 (0.76-0.97). The HR (95 % CIs) was 0.87 (0.76-0.98) after controlling for measures of adiposity, socio-economic variables, medical history, blood pressure, renal function, alcohol consumption, and lipids. These findings remained consistent in analyses accounting for incident coronary heart disease. The results were comparable across several clinically relevant subgroups and analyses with atrial fibrillation as a competing risk yielded similar results. Serum magnesium was continuously, inversely and independently associated with future risk of HF. Further research is needed to assess any potential relevance of serum magnesium in HF prevention.
Boyle, Patricia A.; Wilson, Robert S.; Yu, Lei; Buchman, Aron S.; Bennett, David A.
2013-01-01
Background Decision making is thought to be an important determinant of health and well-being across the lifespan, but little is known about the association of decision making with mortality. Methods Participants were 675 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Baseline assessments of decision making were used to predict the risk of mortality during up to 4 years of follow-up. Results The mean score on the decision making measure at baseline was 7.1 (SD=2.9, range: 0-12), with lower scores indicating poorer decision making. During up to 4 years of follow-up (mean=1.7 years), 40 (6% of 675) persons died. In a proportional hazards model adjusted for age, sex, and education, the risk of mortality increased by about 20% for each additional decision making error (HR=1.19, 95% CI 1.07, 1.32, p=0.002). Thus, a person who performed poorly on the measure of decision making (score=3, 10th percentile) was about four times more likely to die compared to a person who performed well (score=11, 90th percentile). Further, the association of decision making with mortality persisted after adjustment for the level of cognitive function. Conclusion Poor decision making is associated with an increased risk of mortality in old age even after accounting for cognitive function. PMID:23364306
Boyle, Patricia A; Wilson, Robert S; Yu, Lei; Buchman, Aron S; Bennett, David A
2013-01-01
Decision making is thought to be an important determinant of health and well-being across the lifespan, but little is known about the association of decision making with mortality. Participants were 675 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Baseline assessments of decision making were used to predict the risk of mortality during up to 4 years of follow-up. The mean score on the decision making measure at baseline was 7.1 (SD = 2.9, range: 0-12), with lower scores indicating poorer decision making. During up to 4 years of follow-up (mean = 1.7 years), 40 (6% of 675) persons died. In a proportional hazards model adjusted for age, sex and education, the risk of mortality increased by about 20% for each additional decision making error (HR = 1.19, 95% CI = 1.07-1.32, p = 0.002). Thus, a person who performed poorly on the measure of decision making (score = 3, 10th percentile) was about 4 times more likely to die compared to a person who performed well (score = 11, 90th percentile). Further, the association of decision making with mortality persisted after adjustment for the level of cognitive function. Poor decision making is associated with an increased risk of mortality in old age even after accounting for cognitive function. Copyright © 2013 S. Karger AG, Basel.
Prospective Predictors of Suicidal Behavior in BPD at 6 Year Follow-up
Soloff, Paul H.; Chiappetta, Laurel
2012-01-01
Objective Recurrent suicidal behavior is a defining characteristic of BPD. Although most patients achieve remission of suicidal behaviors over time, 3% to 10% die by suicide, raising the question of whether there is a high risk suicidal subtype in BPD. We are conducting the first longitudinal study of suicidal behavior in BPD to identify prospective predictors of suicide attempts, and characterize BPD patients at highest risk for suicide completion. Method Demographic, diagnostic, clinical and psychosocial risk factors assessed at baseline were examined for predictive association with medically significant suicide attempts using Cox proportional hazards models. Prospective predictors were defined for subjects completing 6 or more years in the study and compared to earlier intervals. Results Among 90 subjects, 25 (27.8%) made at least one suicide attempt in the interval, most occurring in the first two years. Risk of attempt was increased by: a.) low socioeconomic status, b.) poor psychosocial adjustment, c.) a family history of suicide d.) prior psychiatric hospitalization; e.) absence of any outpatient treatment prior to the attempt. Higher global functioning at baseline decreased risk. Conclusion Risk factors predictive of suicide attempts change over time. Acute stressors such as MDD were predictive only in the short term (12 mos.), while poor psychosocial functioning had persistent and long term effects on suicide risk. Half of BPD patients have poor psychosocial outcomes despite symptomatic improvement. A social and vocational rehabilitation model of treatment is needed to decrease suicide risk and optimize long term outcomes in BPD. PMID:22549208
NASA Technical Reports Server (NTRS)
Sovers, O. J.; Lanyi, G. E.
1994-01-01
To compare the validity of current algorithms that map zenith tropospheric delay to arbitrary elevation angles, 10 different tropospheric mapping functions are used to analyze the current data base of Deep Space Network Mark 3 intercontinental very long baseline interferometric (VLBI) data. This analysis serves as a stringent test because of the high proportion of low-elevation observations necessitated by the extremely long baselines. Postfit delay and delay-rate residuals are examined, as well as the scatter of baseline lengths about the time-linear model that characterizes tectonic motion. Among the functions that utilize surface meteorological data as input parameters, the Lanyi 1984 mapping shows the best performance both for residuals and baselines, through the 1985 Davis function is statistically nearly identical. The next best performance is shown by the recent function of Niell, which is based on an examination of global atmospheric characteristics as a function of season and uses no weather data at the time of the measurements. The Niell function shows a slight improvement in residuals relative to Lanyi, but also an increase in baseline scatter that is significant for the California-Spain baseline. Two variants of the Chao mapping function, as well as the Chao tables used with the interpolation algorithm employed in the Orbit Determination Program software, show substandard behavior for both VLBI residuals and baseline scatter. The length of the California-Australia baseline (10,600 km) in the VLBI solution can vary by as much as 5 to 10 cm for the 10 mapping functions.
Harbeck, N; Iyer, S; Turner, N; Cristofanilli, M; Ro, J; André, F; Loi, S; Verma, S; Iwata, H; Bhattacharyya, H; Puyana Theall, K; Bartlett, C H; Loibl, S
2016-06-01
In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5-67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (-3.3, 95% CI -5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with fulvestrant alone. Palbociclib plus fulvestrant allowed patients to maintain good QoL in the endocrine resistance setting while experiencing substantially delayed disease progression. NCT01942135. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Harbeck, N.; Iyer, S.; Turner, N.; Cristofanilli, M.; Ro, J.; André, F.; Loi, S.; Verma, S.; Iwata, H.; Bhattacharyya, H.; Puyana Theall, K.; Bartlett, C. H.; Loibl, S.
2016-01-01
Background In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2− endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. Patients and methods Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1–4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0–100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. Results Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5–67.7 versus 63.0, 95% CI 60.6–65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (−3.3, 95% CI −5.1 to −1.5 versus 2.0, 95% CI −0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P < 0.025) and pain (P < 0.001) compared with fulvestrant alone. Conclusion Palbociclib plus fulvestrant allowed patients to maintain good QoL in the endocrine resistance setting while experiencing substantially delayed disease progression. Clinical Trial Registration NCT01942135. PMID:27029704
A stereo-vision hazard-detection algorithm to increase planetary lander autonomy
NASA Astrophysics Data System (ADS)
Woicke, Svenja; Mooij, Erwin
2016-05-01
For future landings on any celestial body, increasing the lander autonomy as well as decreasing risk are primary objectives. Both risk reduction and an increase in autonomy can be achieved by including hazard detection and avoidance in the guidance, navigation, and control loop. One of the main challenges in hazard detection and avoidance is the reconstruction of accurate elevation models, as well as slope and roughness maps. Multiple methods for acquiring the inputs for hazard maps are available. The main distinction can be made between active and passive methods. Passive methods (cameras) have budgetary advantages compared to active sensors (radar, light detection and ranging). However, it is necessary to proof that these methods deliver sufficiently good maps. Therefore, this paper discusses hazard detection using stereo vision. To facilitate a successful landing not more than 1% wrong detections (hazards that are not identified) are allowed. Based on a sensitivity analysis it was found that using a stereo set-up at a baseline of ≤ 2 m is feasible at altitudes of ≤ 200 m defining false positives of less than 1%. It was thus shown that stereo-based hazard detection is an effective means to decrease the landing risk and increase the lander autonomy. In conclusion, the proposed algorithm is a promising candidate for future landers.
Physically and psychologically hazardous jobs and mental health in Thailand
Yiengprugsawan, Vasoontara; Strazdins, Lyndall; Lim, Lynette L.-Y.; Kelly, Matthew; Seubsman, Sam-ang; Sleigh, Adrian C.
2015-01-01
This paper investigates associations between hazardous jobs, mental health and wellbeing among Thai adults. In 2005, 87 134 distance-learning students from Sukhothai Thammathirat Open University completed a self-administered questionnaire; at the 2009 follow-up 60 569 again participated. Job characteristics were reported in 2005, psychological distress and life satisfaction were reported in both 2005 and 2009. We derived two composite variables grading psychologically and physically hazardous jobs and reported adjusted odds ratios (AOR) from multivariate logistic regressions. Analyses focused on cohort members in paid work: the total was 62 332 at 2005 baseline and 41 671 at 2009 follow-up. Cross-sectional AORs linking psychologically hazardous jobs to psychological distress ranged from 1.52 (one hazard) to 4.48 (four hazards) for males and a corresponding 1.34–3.76 for females. Similarly AORs for physically hazardous jobs were 1.75 (one hazard) to 2.76 (four or more hazards) for males and 1.70–3.19 for females. A similar magnitude of associations was found between psychologically adverse jobs and low life satisfaction (AORs of 1.34–4.34 among males and 1.18–3.63 among females). Longitudinal analyses confirm these cross-sectional relationships. Thus, significant dose–response associations were found linking hazardous job exposures in 2005 to mental health and wellbeing in 2009. The health impacts of psychologically and physically hazardous jobs in developed, Western countries are equally evident in transitioning Southeast Asian countries such as Thailand. Regulation and monitoring of work conditions will become increasingly important to the health and wellbeing of the Thai workforce. PMID:24218225
COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.
Slade, G D; Sanders, A E; Ohrbach, R; Bair, E; Maixner, W; Greenspan, J D; Fillingim, R B; Smith, S; Diatchenko, L
2015-09-01
When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in adults who developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters. © International & American Associations for Dental Research 2015.
Chow, Benjamin J W; Small, Gary; Yam, Yeung; Chen, Li; McPherson, Ruth; Achenbach, Stephan; Al-Mallah, Mouaz; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Cheng, Victor Y; Chinnaiyan, Kavitha; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gundrun; Hadamitzky, Martin; Hausleiter, Jörg; Karlsberg, Ronald P; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon; LaBounty, Troy; Lin, Fay; Maffei, Erica; Raff, Gilbert L; Shaw, Leslee J; Villines, Todd C; Min, James K
2015-04-01
We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD. URL: http://clinicaltrials.gov/. Unique identifier NCT01443637. © 2015 American Heart Association, Inc.
A small business approach to nanomaterial environment, health, and safety.
Gause, Charles B; Layman, Rachel M; Small, Aaron C
2011-06-01
Integral to the commercialization process for nanotechnology enabled products is the methodology for protecting workers potentially exposed to nanomaterials during product development. Occupational health surveillance is a key aspect of protecting employees and involves both hazard identification and surveillance of known medical data. However, when the health effects and exposure pathways of both new and existing "nano-scale" chemical substances are not yet well understood, conservative hazard controls and baseline data collection can facilitate both immediate and long-term worker protection. Luna Innovations uses a conservative approach based on risk assessment and the OSHA General Duty Clause. To date, Luna's approach has been effective for our business model. Understanding and managing potential hazards to our nanotechnology workers is key to the success and acceptance of nanotechnology enabled products.
Lee, Christina S.; Almeida, Joanna; Colby, Suzanne M.; Tavares, Tonya; Rohsenow, Damaris J.
2015-01-01
Background Among Hispanics in the U.S., lower acculturation level has been found to be protective against alcohol abuse and depression. However, this relationship may not hold within at-risk samples. The prevalence and co-occurrence of hazardous drinking and depressive symptoms and their relationship to acculturation were examined among Hispanics enrolled in a study to reduce heavy drinking. At enrollment, all participants reported past-month heavy drinking (one or more occasions of >4/5 drinks for females/males, and average weekly consumption >7/14 drinks per week). We explored whether gender moderated the effects of acculturation on hazardous drinking and depressive symptoms. Methods Participants (N = 100) completed measures at baseline. Results Eighty-nine percent of participants met criteria for hazardous alcohol use as assessed by the AUDIT and of those, 55% (n=49) also reported elevated depressive symptoms. Of those who reported elevated depressive symptoms, nearly all (94%) met AUDIT criteria for hazardous drinking. Acculturation was not related to hazardous drinking or depressive symptoms in the full sample. Highly acculturated women reported more hazardous drinking than less acculturated women. Acculturation was not associated with hazardous drinking in men, but less acculturated men reported higher levels of depression than highly acculturated men. Discussion Depression should be assessed in alcohol interventions for Hispanics. Alcohol interventions should be tailored for acculturation level and gender to improve relevance and efficacy. Clinical Trial Registration #NCT01996280. PMID:26819573
Step 1: Human System Integration Pilot-Technology Interface Requirements for Weather Management
NASA Technical Reports Server (NTRS)
2005-01-01
This document involves definition of technology interface requirements for Hazardous Weather Avoidance. Technology concepts in use by the Access 5 Weather Management Work Package were considered. Beginning with the Human System Integration (HIS) high-level functional requirement for Hazardous Weather Avoidance, and Hazardous Weather Avoidance technology elements, HSI requirements for the interface to the pilot were identified. Results of the analysis describe (1) the information required by the pilot to have knowledge of hazardous weather, and (2) the control capability needed by the pilot to obtain hazardous weather information. Fundamentally, these requirements provide the candidate Hazardous Weather Avoidance technology concepts with the necessary human-related elements to make them compatible with human capabilities and limitations. The results of the analysis describe how Hazardous Weather Avoidance operations and functions should interface with the pilot to provide the necessary Weather Management functionality to the UA-pilot system. Requirements and guidelines for Hazardous Weather Avoidance are partitioned into four categories: (1) Planning En Route (2) Encountering Hazardous Weather En Route, (3) Planning to Destination, and (4) Diversion Planning Alternate Airport. Each requirement is stated and is supported with a rationale and associated reference(s).
The predictive value of mean serum uric acid levels for developing prediabetes.
Zhang, Qing; Bao, Xue; Meng, Ge; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Huang, Guowei; Song, Kun; Niu, Kaijun
2016-08-01
We aimed to assess the predictive value of mean serum uric acid (SUA) levels for incident prediabetes. Normoglycemic adults (n=39,353) were followed for a median of 3.0years. Prediabetes is defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired HbA1c (IA1c), based on the American Diabetes Association criteria. Serum SUA levels were measured annually. Four diagnostic strategies were used to detect prediabetes in four separate analyses (Analysis 1: IFG. Analysis 2: IFG+IGT. Analysis 3: IFG+IA1c. Analysis 4: IFG+IGT+IA1c). Cox proportional hazards regression models were used to assess the relationship between SUA quintiles and prediabetes. C-statistic was additionally used in the final analysis to assess the accuracy of predictions based upon baseline SUA and mean SUA, respectively. After adjustment for potential confounders, the hazard ratios (95% confidence interval) of prediabetes for the highest versus lowest quintile of mean SUA were 1.22 (1.10, 1.36) in analysis 1; 1.59 (1.23, 2.05) in analysis 2; 1.62 (1.34, 1.95) in analysis 3 and 1.67 (1.31, 2.13) in analysis 4. In contrast, for baseline SUA, significance was only reached in analyses 3 and 4. Moreover, compared with baseline SUA, mean SUA value was associated with a significant increase in the C-statistic (P<0.001). Mean SUA value was strongly and positively related to prediabetes risk, and showed better predictive ability for prediabetes than baseline SUA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lessin, Lawrence S; Kamensky, Victor; Lin, Juan; Wassertheil-Smoller, Sylvia; Rohan, Thomas E
2016-05-15
Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Hazard Function Estimation with Cause-of-Death Data Missing at Random
Wang, Qihua; Dinse, Gregg E.; Liu, Chunling
2010-01-01
Hazard function estimation is an important part of survival analysis. Interest often centers on estimating the hazard function associated with a particular cause of death. We propose three nonparametric kernel estimators for the hazard function, all of which are appropriate when death times are subject to random censorship and censoring indicators can be missing at random. Specifically, we present a regression surrogate estimator, an imputation estimator, and an inverse probability weighted estimator. All three estimators are uniformly strongly consistent and asymptotically normal. We derive asymptotic representations of the mean squared error and the mean integrated squared error for these estimators and we discuss a data-driven bandwidth selection method. A simulation study, conducted to assess finite sample behavior, demonstrates that the proposed hazard estimators perform relatively well. We illustrate our methods with an analysis of some vascular disease data. PMID:22267874
Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie
2015-03-14
The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .
Al-Batran, S-E; Van Cutsem, E; Oh, S C; Bodoky, G; Shimada, Y; Hironaka, S; Sugimoto, N; Lipatov, O N; Kim, T-Y; Cunningham, D; Rougier, P; Muro, K; Liepa, A M; Chandrawansa, K; Emig, M; Ohtsu, A; Wilke, H
2016-04-01
The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. NCT01170663. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Crandall, Carolyn J; Yildiz, Vedat O; Wactawski-Wende, Jean; Johnson, Karen C; Chen, Zhao; Going, Scott B; Wright, Nicole C; Cauley, Jane A
2015-01-27
To determine associations between postmenopausal change in body weight and incidence of fracture and associations between voluntary and involuntary weight loss and risk of fracture. Post hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials. 40 clinical centers in the United States. 120,566 postmenopausal women, aged 50-79 at baseline (1993-98), followed through 2013 (mean fracture follow-up duration 11 years from baseline). Annualized percentage change in measured body weight from baseline to year 3, classified as stable (<5% change), weight loss (≥ 5%), or weight gain (≥ 5%). Self assessment of whether weight loss was intentional or unintentional. Cox proportional hazards regression models were adjusted for age, race/ethnicity, baseline body mass index (BMI), smoking, alcohol intake, level of physical activity, energy expenditure, calcium and vitamin D intake, physical function score, oophorectomy, hysterectomy, previous fracture, comorbidity score, and drug use. Incident self reported fractures of the upper limbs, lower limbs, and central body; hip fractures confirmed by medical records. Mean participant age was 63.3. Mean annualized percent weight change was 0.30% (95% confidence interval 0.28 to 0.32). Overall, 79,279 (65.6%) had stable weight; 18,266 (15.2%) lost weight; and 23,021 (19.0%) gained weight. Compared with stable weight, weight loss was associated with a 65% higher incidence rates of fracture in hip (adjusted hazard ratio 1.65, 95% confidence interval 1.49 to 1.82), upper limb (1.09, 1.03 to 1.16), and central body (1.30, 1.20 to 1.39); weight gain was associated with higher incidence rates of fracture in upper limb (1.10, 1.05 to 1.18) and lower limb (1.18, 1.12 to 1.25). Compared with stable weight, unintentional weight loss was associated with a 33% higher incidence rates of hip fracture (1.33, 1.19 to 1.47) and increased incidence rates of vertebral fracture (1.16, 1.06 to 1.26); intentional weight loss was associated with increased incidence rates of lower limb fracture (1.11, 1.05 to 1.17) and decreased incidence of hip fracture (0.85, 0.76 to 0.95). Weight gain, weight loss, and intentional weight loss are associated with increased incidence of fracture, but associations differ by fracture location. Clinicians should be aware of fracture patterns after weight gain and weight loss. © Crandall et al 2015.
Long-term effects of functional impairment on fracture risk and mortality in postmenopausal women.
Rikkonen, T; Poole, K; Sirola, J; Sund, R; Honkanen, R; Kröger, H
2018-06-02
Our findings imply that simple functional tests can predict both hip fracture risk and excess mortality in postmenopausal women. Since the tests characterize general functional capacity (one-legged stance, squatting down, and grip strength), these simple measures should have clinical utility in the assessment of women at risk of falls and fragility fracture. Functional impairment is associated with the risk of fall, which is the leading cause of hip fracture. We aimed to determine how clinical assessments of functional impairment predict long-term hip fracture and mortality. A population-based prospective cohort involved 2815 Caucasian women with the average baseline age of 59.1 years. The mean follow-up time in 1994-2014 was 18.3 years. Three functional tests and their combinations assessed at baseline were treated as dichotomous risk factors: (1) inability to squat down and touch the floor (SQ), (2) inability to stand on one leg for 10 s (SOL), and (3) having grip strength (GS) within the lowest quartile (≤ 58 kPa, mean 45.6 kPa). Bone mineral density (BMD) at the proximal femur was measured by DXA. Fractures and deaths were verified from registries. Hazard ratios were determined by using Cox proportional models. Age, body mass index (BMI), and BMD were included as covariates for fracture risk estimates. Age, BMI, and smoking were used for mortality. Altogether, 650 (23.1%) women had 718 follow-up fractures, including 86 hip fractures. The mortality during the follow-up was 16.8% (n = 473). Half of the women (56.8%, n = 1600) had none of the impairments and were regarded as the referent group. Overall, women with any of the three impairments (43.2%, n = 1215) had higher risks of any fracture, hip fracture, and death, with hazard ratios (HR) of 1.3 ((95% CI) 1.0-1.5, p < 0.01), 2.4 (1.5-3.4, p < 0.001), and 1.5 (1.3-1.8, p < 0.001), respectively. The strongest single predictor for hip fracture was failing to achieve a one-leg stand for 10 s (prevalence 7.1%, n = 200), followed by inability to squat down (27.0%, n = 759) and weak grip strength (24.4%, n = 688), with their respective HRs of 4.3 (2.3-8.0, p < 0.001), 3.1 (2.0-5.0, p < 0.001), and 2.0 (1.2-3.4, p < 0.001). In addition, age, lower BMD, BMI, and smoking were significant covariates. These findings suggest that functional tests provide long-term prediction of fracture and death in postmenopausal women. Whether reversal of these impairments is associated with a reduction in adverse outcomes is an area for future trials.
Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia.
Trobec, Katja; Palus, Sandra; Tschirner, Anika; von Haehling, Stephan; Doehner, Wolfram; Lainscak, Mitja; Anker, Stefan D; Springer, Jochen
2014-09-01
Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P < 0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function. Copyright © 2014 Elsevier Inc. All rights reserved.
Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Mejía, Mayra; Rivero, Hermes; Mateos-Toledo, Heidegger; Figueroa, José E
2015-09-01
The objectives of the present study were to compare the survival function of antisynthetase syndrome (ASS) Jo1-positive patients with ASS non-Jo1 patients, all with interstitial lung disease (ILD), and to evaluate other factors such as the extension of pulmonary disease and the time between the onset of symptoms and diagnosis and its association to survival in a cohort of ASS patients. Patients with ASS, all with ILD, were included. At the baseline, pulmonary function tests were realized and a high-resolution chest tomography was obtained; lung inflammation and fibrosis were measured with the Goh score and the Kazerooni index. The following autoantibodies were measured: Jo1, Ej, Oj, PL7, and PL12. Patients had to be positive for one of them in order to be included in the study. The survival function was estimated and compared with the log rank test, and the hazard ratio (HR) was estimated using Cox regression procedure. Forty-three patients were included, of which six patients died (14 %). Patients who died were different in comparison with survivors as regards the frequency of anti-Jo1 positivity: Survivors had anti-Jo1 autoantibodies more frequently (86 %) than patients who died (50 %). The univariate Cox regression analysis identified four variables associated with survival: Jo1 status, arthritis, extent of ground glass, and consolidation (inflammation) in high-resolution computed tomography (HRCT) and baseline forced vital capacity. The serological status of patients (Jo1-positive vs non-Jo1), the extent of lung inflammation in the HRCT scan, a low forced vital capacity, and arthritis are associated with survival in ASS patients.
Cawthon, Peggy M; Blackwell, Terri L; Cauley, Jane; Kado, Deborah M; Barrett-Connor, Elizabeth; Lee, Christine G; Hoffman, Andrew R; Nevitt, Michael M; Stefanick, Marcia L; Lane, Nancy E; Ensrud, Kristine E; Cummings, Steven R; Orwoll, Eric S
2016-01-01
Background Recently, several consensus definitions for sarcopenia have been developed. Objective To evaluate the associations and discriminative ability of definitions of sarcopenia against clinical outcomes. Design Osteoporotic Fractures in Men study Setting Six clinical centers Participants 5,934 community-dwelling men aged ≥65 yrs Measurements Sarcopenia definitions evaluated were: International Working Group (IWG), European Working Group for Sarcopenia in Older Persons (EWGSOP), Foundation for the NIH (FNIH) Sarcopenia, Baumgartner, and Newman. Recurrent falls were defined as ≥2 self-reported falls in the year after baseline (N=694, 11.9%). Incident hip fractures (N=207, 3.5 %) and deaths (N=2003, 34.1%) were confirmed by central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and again 4.6 years later. Logistic regression or proportional hazards models estimated associations between sarcopenia and falls, hip fractures or death. The discriminative ability of the sarcopenia definitions (compared to referent models) for these outcomes was evaluated with areas under the receiver operator curve (AUCs) or C-statistics. Referent models included age alone for falls, function limitations and mortality, and age and BMD for hip fractures. Results The association between sarcopenia by the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with increased mortality risk. However, none of the definitions materially changed discrimination based on AUC and C-statistic when compared to referent models (change ≤1% in all models). Conclusions Sarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men. PMID:26502831
Udina, M; Navinés, R; Egmond, E; Oriolo, G; Langohr, K; Gimenez, D; Valdés, M; Gómez-Gil, E; Grande, I; Gratacós, M; Kapczinski, F; Artigas, F; Vieta, E; Solà, R
2016-01-01
Background: The role of inflammation in mood disorders has received increased attention. There is substantial evidence that cytokine therapies, such as interferon alpha (IFN-alpha), can induce depressive symptoms. Indeed, proinflammatory cytokines change brain function in several ways, such as altering neurotransmitters, the glucocorticoid axis, and apoptotic mechanisms. This study aimed to evaluate the impact on mood of initiating IFN-alpha and ribavirin treatment in a cohort of patients with chronic hepatitis C. We investigated clinical, personality, and functional genetic variants associated with cytokine-induced depression. Methods: We recruited 344 Caucasian outpatients with chronic hepatitis C, initiating IFN-alpha and ribavirin therapy. All patients were euthymic at baseline according to DSM-IV-R criteria. Patients were assessed at baseline and 4, 12, 24, and 48 weeks after treatment initiation using the Patient Health Questionnaire (PHQ), the Hospital Anxiety and Depression Scale (HADS), and the Temperament and Character Inventory (TCI). We genotyped several functional polymorphisms of interleukin-28 (IL28B), indoleamine 2,3-dioxygenase (IDO-1), serotonin receptor-1A (HTR1A), catechol-O-methyl transferase (COMT), glucocorticoid receptors (GCR1 and GCR2), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5) genes. A survival analysis was performed, and the Cox proportional hazards model was used for the multivariate analysis. Results: The cumulative incidence of depression was 0.35 at week 24 and 0.46 at week 48. The genotypic distributions were in Hardy-Weinberg equilibrium. Older age (p = 0.018, hazard ratio [HR] per 5 years = 1.21), presence of depression history (p = 0.0001, HR = 2.38), and subthreshold depressive symptoms at baseline (p = 0.005, HR = 1.13) increased the risk of IFN-induced depression. So too did TCI personality traits, with high scores on fatigability (p = 0.0037, HR = 1.17), impulsiveness (p = 0.0200 HR = 1.14), disorderliness (p = 0.0339, HR = 1.11), and low scores on extravagance (p = 0.0040, HR = 0.85). An interaction between HTR1A and COMT genes was found. Patients carrying the G allele of HTR1A plus the Met substitution of the COMT polymorphism had a greater risk for depression during antiviral treatment (HR = 3.83) than patients with the CC (HTR1A) and Met allele (COMT) genotypes. Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype. Moreover, functional variants of the GCR1 (GG genotype: p = 0.0436, HR = 1.88) and BDNF genes (Val/Val genotype: p = 0.0453, HR = 0.55) were associated with depression. Conclusions: The results of the study support the theory that IFN-induced depression is associated with a complex pathophysiological background, including serotonergic and dopaminergic neurotransmission as well as glucocorticoid and neurotrophic factors. These findings may help to improve the management of patients on antiviral treatment and broaden our understanding of the pathogenesis of mood disorders. PMID:26721949
McCullough, Marjorie L; Jacobs, Eric J; Shah, Roma; Campbell, Peter T; Wang, Ying; Hartman, Terryl J; Gapstur, Susan M
2018-01-01
Prospective cohort studies suggest that red and processed meat consumption is associated with increased risk of pancreatic cancer among men, but not women. However, evidence is limited, and less evidence exists for other types of meat. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for the association of meat consumption, by type, with pancreatic cancer risk among 138,266 men and women in the Cancer Prevention Study-II Nutrition Cohort. Diet was assessed at baseline in 1992, and 10 years earlier, at enrollment into the parent CPS-II mortality cohort. 1,156 pancreatic cancers were verified through 2013. Red meat, processed meat, and fish intake at baseline were not associated with pancreatic cancer risk. However, for long-term red and processed meat consumption (highest quartiles in 1982 and 1992, vs. lowest quartiles), risk appeared different in men [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.90, 1.95] and women (HR 0.72, 95% CI 0.47, 1.10, p heterogeneity by sex = 0.05). Poultry consumption in 1992 was associated with increased pancreatic cancer risk (HR 1.27, 95% CI 1.04, 1.55, p trend = 0.01, top vs. bottom quintile). The associations of meat consumption with pancreatic cancer risk remain unclear and further research, particularly of long-term intake, is warranted.
Healthy eating and reduced risk of cognitive decline
Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim
2015-01-01
Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720
Yoon, Chang-Yun; Noh, Juhwan; Jhee, Jong Hyun; Chang, Tae Ik; Kang, Ea Wha; Kee, Youn Kyung; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jung, Su-Young; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Kim, Changsoo; Yoo, Tae-Hyun
2017-09-01
The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications. © 2017 American Heart Association, Inc.
Estimation of Dog-Bite Risk and Related Morbidity Among Personnel Working With Military Dogs.
Schermann, H; Eiges, N; Sabag, A; Kazum, E; Albagli, A; Salai, M; Shlaifer, A
Soldiers serving in the Israel Defense Force Military Working Dogs (MWD) Unit spend many hours taming dogs' special skills, taking them on combat missions, and performing various dogkeeping activities. During this intensive work with the aggressive military dogs, bites are common, and some of them result in permanent disability. However, this phenomenon has not been quantified or reported as an occupational hazard. This was a retrospective cohort study based on self-administered questionnaires. Information was collected about soldiers' baseline demographics, duration of the experience of working with dogs, total number of bites they had, circumstances of bite events, and complications and medical treatment of each bite. Bite risk was quantified by incidence, mean time to first bite, and a Cox proportional hazards model. Rates of complications and the medical burden of bites were compared between combat soldiers and noncombat dogkeepers. Bite locations were presented graphically. Seventy-eight soldiers participated and reported on 139 bites. Mean time of working with dogs was 16 months (standard deviation, ±9.4 months). Overall bite incidence was 11 bites per 100 person-months; the mean time to first bite event was 6.3 months. The Cox proportional hazards model showed that none of baseline characteristics significantly increased bite hazard. About 90% of bites occurred during routine activities, and 3.3% occurred on combat missions. Only in 9% of bite events did soldiers observed the safety precautions code. Bite complications included fractures, need for intravenous antibiotic treatment and surgical repair, prominent scarring, diminished sensation, and stiffness of proximal joints. Bite complications were similar between combat soldiers and dogkeepers. Most bites (57%) were located on hands and arms. MWD bites are an occupational hazard resulting in significant medical burden. Hands and arms were most common bite locations. Observance of safety precautions may be the most appropriate first-line preventive intervention. Barrier protection of upper extremities may reduce bite severity and complication rates. 2017.
Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and Older Wage Workers
2014-01-01
Objectives Many studies have reported an association between overwork and hypertension. However, research on the health effects of long working hours has yielded inconclusive results. The objective of this study was to identify an association between overtime work and hypertension in wage workers 45 years and over of age using prospective data. Methods Wage workers in Korea aged 45 years and over were selected for inclusion in this study from among 10,254 subjects from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension and those with other major diseases were excluded. In the end, a total of 1,079 subjects were included. A Cox proportional hazards model was used to calculate hazard ratios and adjust for baseline characteristics such as sex, age, education, income, occupation, form of employment, body mass index, alcohol habit, smoking habit, regular exercise, and number of working days per week. Additional models were used to calculate hazard ratios after gender stratification. Results Among the 1,079 subjects, 85 workers were diagnosed with hypertension during 3974.2 person-months. The average number of working hours per week for all subjects was 47.68. The proportion of overtime workers was 61.0% (cutoff, 40 h per week). Compared with those working 40 h and less per week, the hazard ratio of subjects in the final model, which adjusted for all selected variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19–4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07–5.39), and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33–6.20). In gender stratification models, the hazard ratio of the females tended to be higher than that of the males. Conclusion As the number of working hours per week increased, the hazard ratio for diagnosis of hypertension significantly increased. This result suggests a positive association between overtime work and the risk of hypertension. PMID:25852938
Effect of Long Working Hours on Self-reported Hypertension among Middle-aged and Older Wage Workers.
Yoo, Dong Hyun; Kang, Mo-Yeol; Paek, Domyung; Min, Bokki; Cho, Sung-Il
2014-01-01
Many studies have reported an association between overwork and hypertension. However, research on the health effects of long working hours has yielded inconclusive results. The objective of this study was to identify an association between overtime work and hypertension in wage workers 45 years and over of age using prospective data. Wage workers in Korea aged 45 years and over were selected for inclusion in this study from among 10,254 subjects from the Korean Longitudinal Study of Ageing. Workers with baseline hypertension and those with other major diseases were excluded. In the end, a total of 1,079 subjects were included. A Cox proportional hazards model was used to calculate hazard ratios and adjust for baseline characteristics such as sex, age, education, income, occupation, form of employment, body mass index, alcohol habit, smoking habit, regular exercise, and number of working days per week. Additional models were used to calculate hazard ratios after gender stratification. Among the 1,079 subjects, 85 workers were diagnosed with hypertension during 3974.2 person-months. The average number of working hours per week for all subjects was 47.68. The proportion of overtime workers was 61.0% (cutoff, 40 h per week). Compared with those working 40 h and less per week, the hazard ratio of subjects in the final model, which adjusted for all selected variables, working 41-50 h per week was 2.20 (95% confidence interval [CI], 1.19-4.06), that of subjects working 51-60 h per week was 2.40 (95% CI, 1.07-5.39), and that of subjects working 61 h and over per week was 2.87 (95% CI, 1.33-6.20). In gender stratification models, the hazard ratio of the females tended to be higher than that of the males. As the number of working hours per week increased, the hazard ratio for diagnosis of hypertension significantly increased. This result suggests a positive association between overtime work and the risk of hypertension.
Shikanov, Sergey A; Eng, Michael K; Bernstein, Andrew J; Katz, Mark; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C
2008-08-01
We evaluated urinary and sexual quality of life 1 year following robotic laparoscopic radical prostatectomy and identified preoperative variables predictive of a severe decrease from baseline. Using a prospective robotic laparoscopic radical prostatectomy database we identified patients with greater than 1 year of postoperative followup. The UCLA-PCI SF-36v2 questionnaire was used to evaluate urinary and sexual quality of life before and 1 year after surgery. Severe worsening of the postoperative score was defined as a greater than 1 SD decrease. Demographic and preoperative clinical variables were evaluated along with baseline scores on univariate and multivariate analysis. Between February 2003 and September 2007 a total of 1,225 robotic laparoscopic radical prostatectomies were performed at our center and 361 patients (52%) met inclusion criteria. On multivariate analysis baseline urinary function was the only predictor of significant worsening of urinary function (OR 1.04, p = 0.003). Baseline urinary bother was the only predictor of significant worsening of urinary bother (OR 1.05, p <0.0001). A significant decrease in sexual function was predicted by baseline sexual function (OR 1.03, p = 0.0001), baseline sexual bother (OR 1.03, p = 0.005) and nerve sparing technique (OR 0.31, p = 0.05). Predictors of a significant decrease in sexual bother were also baseline sexual function (OR 1.02, p = 0.0001), baseline sexual bother (OR 1.04, p = 0.0007) and nerve sparing technique (OR 0.38, p = 0.02). ORs indicated that higher baseline scores corresponded to a higher risk of postoperative score worsening. We found that overall better baseline sexual and urinary scores are associated with better postoperative outcomes. However, the risk of a significant decrease in urinary function, urinary bother, sexual function and sexual bother is higher in patients with better baseline scores. Nerve sparing positively affects sexual function and sexual bother.
Correlating regional natural hazards for global reinsurance risk assessment
NASA Astrophysics Data System (ADS)
Steptoe, Hamish; Maynard, Trevor; Economou, Theo; Fox, Helen; Wallace, Emily; Maisey, Paul
2016-04-01
Concurrent natural hazards represent an uncertainty in assessing exposure for the insurance industry. The recently implemented Solvency II Directive requires EU insurance companies to fully understand and justify their capital reserving and portfolio decisions. Lloyd's, the London insurance and reinsurance market, commissioned the Met Office to investigate the dependencies between different global extreme weather events (known to the industry as perils), and the mechanisms for these dependencies, with the aim of helping them assess their compound risk to the exposure of multiple simultaneous hazards. In this work, we base the analysis of hazard-to-hazard dependency on the interaction of different modes of global and regional climate variability. Lloyd's defined 16 key hazard regions, including Australian wildfires, flooding in China and EU windstorms, and we investigate the impact of 10 key climate modes on these areas. We develop a statistical model that facilitates rapid risk assessment whilst allowing for both temporal auto-correlation and, crucially, interdependencies between drivers. The simulator itself is built conditionally using autoregressive regression models for each driver conditional on the others. Whilst the baseline assumption within the (re)insurance industry is that different natural hazards are independent of each other, the assumption of independence of meteorological risks requires greater justification. Although our results suggest that most of the 120 hazard-hazard connections considered are likely to be independent of each other, 13 have significant dependence arising from one or more global modes of climate variability. This allows us to create a matrix of linkages describing the hazard dependency structure that Lloyd's can use to inform their understanding of risk.
NASA Technical Reports Server (NTRS)
Ranaudo, Richard J.; Martos, Borja; Norton, Bill W.; Gingras, David R.; Barnhart, Billy P.; Ratvasky, Thomas P.; Morelli, Eugene
2011-01-01
The utility of the Icing Contamination Envelope Protection (ICEPro) system for mitigating a potentially hazardous icing condition was evaluated by 29 pilots using the NASA Ice Contamination Effects Flight Training Device (ICEFTD). ICEPro provides real time envelope protection cues and alerting messages on pilot displays. The pilots participating in this test were divided into two groups; a control group using baseline displays without ICEPro, and an experimental group using ICEPro driven display cueing. Each group flew identical precision approach and missed approach procedures with a simulated failure case icing condition. Pilot performance, workload, and survey questionnaires were collected for both groups of pilots. Results showed that real time assessment cues were effective in reducing the number of potentially hazardous upset events and in lessening exposure to loss of control following an incipient upset condition. Pilot workload with the added ICEPro displays was not measurably affected, but pilot opinion surveys showed that real time cueing greatly improved their situation awareness of a hazardous aircraft state.
Occupational hazards and illnesses of Filipino women workers in export processing zones.
Lu, Jinky Leilanie
2008-01-01
This was a baseline study on occupational exposure and health problems among women workers in export processing zones. Physical, chemical, and ergonomic hazards were evaluated and measured through workplace ambient monitoring, survey questionnaires, and interviews with 500 respondents in 24 companies (most were female at 88.8%). The top 5 hazards were ergonomic hazards (72.2%), heat (66.6%), overwork (66.6%), poor ventilation (54.8%), and chemical exposure (50.8%). The most common illnesses were gastrointestinal problems (57.4%), backache (56%), headache (53.2%), and fatigue/weakness (53.2%). Logistic regression showed an association between certain work-related factors and occupational illnesses, and psychosocial problems. Highly significant associations were hearing loss with years spent in the company (p=.005) and gender (p=.006), headache and dizziness with poor ventilation (p=.000), backache with prolonged work (p=.003). These results will have implications for policy and program formulation for women workers' concerns and issues in export zones.
Brown, Paul D.; Jaeckle, Kurt; Ballman, Karla V.; Farace, Elana; Cerhan, Jane H.; Anderson, S. Keith; Carrero, Xiomara W.; Barker, Fred G.; Deming, Richard; Burri, Stuart H.; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W.; Pollock, Bruce E.; Galanis, Evanthia; Buckner, Jan C.; Asher, Anthony L.
2017-01-01
IMPORTANCE Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, −0.1 vs −12.0 points; mean difference, 11.9; 95% CI, 4.8–19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2–5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, −1.5 points for SRS alone vs −4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, −2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75–1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, −48.7%; 95% CI, −87.6% to −9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, −34.4%; 95% CI, −74.4% to 5.5%; P = .04). CONCLUSIONS AND RELEVANCE Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00377156 PMID:27458945
Brown, Paul D; Jaeckle, Kurt; Ballman, Karla V; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Barker, Fred G; Deming, Richard; Burri, Stuart H; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L
2016-07-26
Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04). Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. clinicaltrials.gov Identifier: NCT00377156.
A joint frailty-copula model between tumour progression and death for meta-analysis.
Emura, Takeshi; Nakatochi, Masahiro; Murotani, Kenta; Rondeau, Virginie
2017-12-01
Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.
Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M
2016-04-15
Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.
Reilly, Timothy J.; Jones, Daniel K.; Focazio, Michael J.; Aquino, Kimberly C.; Carbo, Chelsea L.; Kaufhold, Erika E.; Zinecker, Elizabeth K.; Benzel, William M.; Fisher, Shawn C.; Griffin, Dale W.; Iwanowicz, Luke R.; Loftin, Keith A.; Schill, William B.
2015-10-26
Coastal communities are uniquely vulnerable to sea-level rise (SLR) and severe storms such as hurricanes. These events enhance the dispersion and concentration of natural and anthropogenic chemicals and pathogenic microorganisms that could adversely affect the health and resilience of coastal communities and ecosystems in coming years. The U.S. Geological Survey has developed a strategy to define baseline and post-event sediment-bound environmental health (EH) stressors (hereafter referred to as the Sediment-Bound Contaminant Resiliency and Response [SCoRR] strategy). A tiered, multimetric approach will be used to (1) identify and map contaminant sources and potential exposure pathways for human and ecological receptors, (2) define the baseline mixtures of EH stressors present in sediments and correlations of relevance, (3) document post-event changes in EH stressors present in sediments, and (4) establish and apply metrics to quantify changes in coastal resilience associated with sediment-bound contaminants. Integration of this information provides a means to improve assessment of the baseline status of a complex system and the significance of changes in contaminant hazards due to storm-induced (episodic) and SLR (incremental) disturbances. This report describes the purpose and design of the SCoRR strategy and the methods used to construct a decision support tool to identify candidate sampling stations vulnerable to contaminants that may be mobilized by coastal storms.
Jakobsen, Lars; Niemann, Troels; Thorsgaard, Niels; Thuesen, Leif; Lassen, Jens F; Jensen, Lisette O; Thayssen, Per; Ravkilde, Jan; Tilsted, Hans H; Mehnert, Frank; Johnsen, Søren P
2012-10-01
The association between low socioeconomic status (SES) and high mortality from coronary heart disease is well-known. However, the role of SES in relation to the clinical outcome after primary percutaneous coronary intervention remains poorly understood. We studied 7385 patients treated with primary percutaneous coronary intervention. Participants were divided into high-SES and low-SES groups according to income, education, and employment status. The primary outcome was major adverse cardiac events (cardiac death, recurrent myocardial infarction, and target vessel revascularization) at maximum follow-up (mean, 3.7 years). Low-SES patients had more adverse baseline risk profiles than high-SES patients. The cumulative risk of major adverse cardiac events after maximum follow-up was higher among low-income patients and unemployed patients compared with their counterparts (income: hazard ratio, 1.68; 95% CI, 1.47-1.92; employment status: hazard ratio, 1.75; 95% CI, 1.46-2.10). After adjustment for patient characteristics, these differences were substantially attenuated (income: hazard ratio, 1.12; 95% CI, 0.93-1.33; employment status: hazard ratio, 1.27; 95% CI, 1.03-1.56). Further adjustment for admission findings, procedure-related data, and medical treatment during follow-up did not significantly affect the associations. With education as the SES indicator, no between-group differences were observed in the risk of the composite end point. Even in a tax-financed healthcare system, low-SES patients treated with primary percutaneous coronary intervention face a worse prognosis than high-SES patients. The poor outcome seems to be largely explained by differences in baseline patient characteristics. Employment status and income (but not education level) were associated with clinical outcomes.
Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults.
Panwar, Bhupesh; Judd, Suzanne E; Warnock, David G; McClellan, William M; Booth, John N; Muntner, Paul; Gutiérrez, Orlando M
2016-08-01
In previous observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults aged ≥45 years. A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (<12.4 g/dL) and highest (>14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke when compared with the second quartile (12.4-13.2 g/dL; quartile 1: hazard ratio, 1.59; 95% confidence interval, 1.09-2.31; quartile 2: referent; quartile 3: hazard ratio, 0.91; 95% confidence interval, 0.59-1.38; quartile 4: hazard ratio, 1.59; 95% confidence interval, 1.08-2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men. © 2016 American Heart Association, Inc.
Psychopathology, cognition and outcome in Dutch and immigrant first-episode psychosis patients.
Stouten, Luyken H; Veling, Wim; Laan, Winfried; Van der Gaag, Mark
2018-03-30
The primary aim was to examine differences in baseline symptom expression, neurocognition, social cognition and psychosocial functioning between Dutch, first-generation immigrants and second-generation immigrants with a first-episode psychosis (FEP). The secondary aim was to examine functional and symptomatic change and between-group differences at 12-months follow-up. Associations between migration, baseline characteristics and outcome were explored. Forty-six Dutch, 56 second-generation- and 60 first-generation immigrant patients completed baseline measures for 6 symptom dimensions (positive symptoms, negative symptoms, neurocognitive functioning, social cognitive functioning, excitement and emotional distress) and 5 domains of psychosocial functioning (general functioning, work and study, relationships, self-care and disturbing behaviour). Functioning and psychotic symptoms were assessed at baseline and 12-months follow-up. ANCOVA and t tests were used to assess between-group differences. General linear models were used to explore within-group differences. Backward-regression was used to explore predictors of outcome. Levels of positive symptoms, excitement and emotional distress did not differ between groups at baseline or follow-up. Dutch patients had lower levels of negative symptoms than both immigrant groups at follow-up. On neurocognition and social cognition, Dutch performed better than second-generation immigrants, who in turn performed better than first-generation immigrants. Psychosocial functioning across all domains at baseline and at 12-months follow-up was similar across groups. Baseline levels of general psychosocial functioning and income were the strongest predictors of outcome at follow-up. Psychosocial functioning and symptom profiles are comparable between Dutch, first-generation immigrant and second-generation immigrant FEP patients, excluding neurocognitive and social cognitive deficits. A range of baseline characteristics predicted outcome. © 2018 John Wiley & Sons Australia, Ltd.
Neuropsychological Correlates of Hazard Perception in Older Adults.
McInerney, Katalina; Suhr, Julie
2016-03-01
Hazard perception, the ability to identify and react to hazards while driving, is of growing importance in driving research, given its strong relationship to real word driving variables. Furthermore, although poor hazard perception is associated with novice drivers, recent research suggests that it declines with advanced age. In the present study, we examined the neuropsychological correlates of hazard perception in a healthy older adult sample. A total of 68 adults age 60 and older who showed no signs of dementia and were active drivers completed a battery of neuropsychological tests as well as a hazard perception task. Tests included the Repeatable Battery for the Assessment of Neuropsychological Status, Wechsler Test of Adult Reading, Trail Making Test, Block Design, Useful Field of View, and the Delis-Kaplan Executive Function System Color Word Interference Test. Hazard perception errors were related to visuospatial/constructional skills, processing speed, memory, and executive functioning skills, with a battery of tests across these domains accounting for 36.7% of the variance in hazard perception errors. Executive functioning, particularly Trail Making Test part B, emerged as a strong predictor of hazard perception ability. Consistent with prior work showing the relationship of neuropsychological performance to other measures of driving ability, neuropsychological performance was associated with hazard perception skill. Future studies should examine the relationship of neuropsychological changes in adults who are showing driving impairment and/or cognitive changes associated with Mild Cognitive Impairment or dementia.
Physically and psychologically hazardous jobs and mental health in Thailand.
Yiengprugsawan, Vasoontara; Strazdins, Lyndall; Lim, Lynette L-Y; Kelly, Matthew; Seubsman, Sam-ang; Sleigh, Adrian C
2015-09-01
This paper investigates associations between hazardous jobs, mental health and wellbeing among Thai adults. In 2005, 87 134 distance-learning students from Sukhothai Thammathirat Open University completed a self-administered questionnaire; at the 2009 follow-up 60 569 again participated. Job characteristics were reported in 2005, psychological distress and life satisfaction were reported in both 2005 and 2009. We derived two composite variables grading psychologically and physically hazardous jobs and reported adjusted odds ratios (AOR) from multivariate logistic regressions. Analyses focused on cohort members in paid work: the total was 62 332 at 2005 baseline and 41 671 at 2009 follow-up. Cross-sectional AORs linking psychologically hazardous jobs to psychological distress ranged from 1.52 (one hazard) to 4.48 (four hazards) for males and a corresponding 1.34-3.76 for females. Similarly AORs for physically hazardous jobs were 1.75 (one hazard) to 2.76 (four or more hazards) for males and 1.70-3.19 for females. A similar magnitude of associations was found between psychologically adverse jobs and low life satisfaction (AORs of 1.34-4.34 among males and 1.18-3.63 among females). Longitudinal analyses confirm these cross-sectional relationships. Thus, significant dose-response associations were found linking hazardous job exposures in 2005 to mental health and wellbeing in 2009. The health impacts of psychologically and physically hazardous jobs in developed, Western countries are equally evident in transitioning Southeast Asian countries such as Thailand. Regulation and monitoring of work conditions will become increasingly important to the health and wellbeing of the Thai workforce. © The Author 2013. Published by Oxford University Press.
The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure.
Ahmad, Tariq; Fiuzat, Mona; Mark, Daniel B; Neely, Ben; Neely, Megan; Kraus, William E; Kitzman, Dalane W; Whellan, David J; Donahue, Mark; Zannad, Faiez; Piña, Ileana L; Adams, Kirkwood; O'Connor, Christopher M; Felker, G Michael
2014-02-01
Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear. Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP (P = .10), hs-CRP (P = .80), or detectable cTnT levels (P = .83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 (P < .001) at 3 months and decreased risk of hospitalizations or mortality (P ≤ .04), even after adjustment for a comprehensive set of known predictors. Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events. © 2014.
Gender and Racial Disparities in Life-Space Constriction Among Older Adults.
Choi, Moon; O'Connor, Melissa L; Mingo, Chivon A; Mezuk, Briana
2016-12-01
"Life-space" is the spatial area through which a person experiences and interacts with the world. Life-space constriction, the shrinking of the spatial area that a person traverses, is associated with negative health outcomes in later life. Racial and gender disparities in mobility as indicated by life-space constriction are thought to contribute to broader disparities in health and functioning among older adults. Data come from the 5-year follow-up of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (N = 2,765; mean age = 73.6; 75.8% women; 73.7% White). Life-space constriction was defined as "not traveling beyond one's town." A series of logistic regression and Cox proportional hazard models were used to estimate risk for incident life-space constriction by race and gender. Blacks and women had greater likelihood of life-space constriction at baseline. Women were more likely to experience incident life-space constriction at follow-up relative to men (Hazard ratio [HR]: 1.89, 95% Confidence interval [CI]: 1.26-2.83). Blacks were associated with lower risk of life-space constriction over time (HR: 0.67, 95% CI: 0.45-0.99) relative to Whites. Disparities in life-space constriction by gender and race exist in later life. Understanding the processes underlying these mobility restrictions is important to developing intervention programs to enhance health and functioning for older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Fedirko, V.; Trichopolou, A.; Bamia, C.; Duarte-Salles, T.; Trepo, E.; Aleksandrova, K.; Nöthlings, U.; Lukanova, A.; Lagiou, P.; Boffetta, P.; Trichopoulos, D.; Katzke, V. A.; Overvad, K.; Tjønneland, A.; Hansen, L.; Boutron-Ruault, M. C.; Fagherazzi, G.; Bastide, N.; Panico, S.; Grioni, S.; Vineis, P.; Palli, D.; Tumino, R.; Bueno-de-Mesquita, H. B.; Peeters, P. H.; Skeie, G.; Engeset, D.; Parr, C. L.; Jakszyn, P.; Sánchez, M. J.; Barricarte, A.; Amiano, P.; Chirlaque, M.; Quirós, J. R.; Sund, M.; Werner, M.; Sonestedt, E.; Ericson, U.; Key, T. J.; Khaw, K. T.; Ferrari, P.; Romieu, I.; Riboli, E.; Jenab, M.
2013-01-01
Background While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations. Methods The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case–control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured. Results HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74–0.95 and HR = 0.80, 95% CI 0.69–0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66–1.11 and RR = 0.74, 95% CI 0.50–1.09, respectively) in a nested case–control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk. Conclusions In this large European cohort, total fish intake is associated with lower HCC risk. PMID:23670094
Hall, Michelle; Hinman, Rana S; van der Esch, Martin; van der Leeden, Marike; Kasza, Jessica; Wrigley, Tim V; Metcalf, Ben R; Dobson, Fiona; Bennell, Kim L
2017-12-08
Clinical guidelines recommend knee muscle strengthening exercises to improve physical function. However, the amount of knee muscle strength increase needed for clinically relevant improvements in physical function is unclear. Understanding how much increase in knee muscle strength is associated with improved physical function could assist clinicians in providing appropriate strength gain targets for their patients in order to optimise outcomes from exercise. The aim of this study was to investigate whether an increase in knee muscle strength is associated with improved self-reported physical function following exercise; and whether the relationship differs according to physical function status at baseline. Data from 100 participants with medial knee osteoarthritis enrolled in a 12-week randomised controlled trial comparing neuromuscular exercise to quadriceps strengthening exercise were pooled. Participants were categorised as having mild, moderate or severe physical dysfunction at baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical function (dependent variable) and peak isometric knee extensor and flexor strength (independent variables) were evaluated with and without accounting for baseline physical function status and covariates using linear regression models. In covariate-adjusted models without accounting for baseline physical function, every 1-unit (Nm/kg) increase in knee extensor strength was associated with physical function improvement of 17 WOMAC units (95% confidence interval (CI) -29 to -5). When accounting for baseline severity of physical function, every 1-unit increase in knee extensor strength was associated with physical function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with severe physical dysfunction. There were no associations between change in strength and change in physical function in participants with mild or moderate physical dysfunction at baseline. The association between change in knee flexor strength and change in physical function was not significant, irrespective of baseline function status. In patients with severe physical dysfunction, an increase in knee extensor strength and improved physical function were associated. ANZCTR 12610000660088 . Registered 12 August 2010.
Norton, J; Portet, F; Gabelle, A; Debette, S; Ritchie, K; Touchon, J; Berr, C
2016-09-01
There is evidence that migraine is a risk factor for stroke but little is known about this association in elderly people. Furthermore, non-migrainous headache (NMH) has received little attention despite being the most frequently reported type of headache. Late-life migraine and NMH were examined as candidate risk factors for stroke in a community-dwelling elderly sample over a 12-year follow-up. One thousand nine hundred and nineteen non-institutionalized subjects aged 65+, without dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, DSM-IV criteria) and with no stroke history at baseline, were drawn from the Three-City Montpellier cohort (recruitment 1999-2001) for longitudinal analysis. Ischaemic and haemorrhagic stroke was reported at baseline and at each of the five follow-ups, with cases validated by a panel of experts, according to ICD-10 criteria (International Classification of Diseases, 10th revision). Migraine and NMH were determined at baseline during a neurological interview and examination using 1988 International Headache Society criteria. A total of 110 (5.4%) cases of migraine and 179 (8.9%) cases of NMH were identified at baseline. During the median 8.8-year follow-up, incident stroke was observed in 1.9% of baseline migrainers, 6.2% of NMH and 3.6% of those with no lifetime history of headache. Cox proportional hazard models indicated that migraine was not a risk factor for stroke; however, NMH sufferers were twice as likely to have a stroke (hazard ratio 2.00, 95% confidence interval 1.00-3.93, P = 0.049). This study is one of the first to suggest that late-life NMH rather than migraine could be an independent risk factor for stroke and a warning sign. The incidence of stroke in elderly migrainers, seldom reported, is particularly low. © 2016 EAN.
Myopia Development Among Young Schoolchildren: The Myopia Investigation Study in Taipei.
Tsai, Der-Chong; Fang, Shao-You; Huang, Nicole; Hsu, Chih-Chien; Chen, Shing-Yi; Chiu, Allen Wen-Hsiang; Liu, Catherine Jui-Ling
2016-12-01
To investigate the annual incidence of myopia and associated factors among young schoolchildren in Taipei City. The Myopia Investigation Study in Taipei was a citywide, population-based cohort study. During the fall 2013 semester (baseline), a total of 11,590 grade 2 schoolchildren completed ocular examination and were included for further analysis. A parent-completed questionnaire was administered to collect data on risk factors for myopia development. Follow-up visits were arranged biannually over 3 years. The first-year results are reported here. Schoolchildren who were emmetropic/hyperopic at baseline and had myopia (spherical equivalent ≤ -0.5 diopters) in either eye at follow-up were identified as having incident myopia. Among 7376 baseline nonmyopic participants, 6794 (92.1%) were examined during the first-year follow-up, and 1856 (25.2%) with incident myopia were identified. The incidence density of myopia was 31.7 (95% confidence interval [CI]: 30.6-32.8) per 100 person-years. Cox hazard proportional regression analysis revealed that participants who were emmetropic at baseline (hazards ratio [HR]: 19.37; 95% CI: 4.84-77.57), who had two myopic parents (HR: 1.21; 95% CI: 1.04-1.42), and who spent ≥5 hours every week on after-school tutoring programs (HR: 1.12; 95% CI: 1.02-1.22) had greater risk for incident myopia. By contrast, protective factors included suburban area of residence (HR: 0.91; 95% CI: 0.83-1.00) and spending ≥30 minutes outdoors after school every weekday (HR: 0.90; 95% CI: 0.82-0.99). This study provides population-based data on the annual incidence of myopia among Taiwanese schoolchildren, and found that baseline refractive status, parental myopia, area of residence, time outdoors after school on weekdays, and time spent on after-school tutoring programs are associated with risk of new-onset myopia.
Orchard, Tonya; Yildiz, Vedat; Steck, Susan E; Hébert, James R; Ma, Yunsheng; Cauley, Jane A; Li, Wenjun; Mossavar-Rahmani, Yasmin; Johnson, Karen C; Sattari, Maryam; LeBoff, Meryl; Wactawski-Wende, Jean; Jackson, Rebecca D
2017-01-01
Previous studies suggest that bone loss and fracture risk are associated with higher inflammatory milieu, potentially modifiable by diet. The primary objective of this analysis was to evaluate the association of the dietary inflammatory index (DII), a measure of the inflammatory potential of diet, with risk of hip, lower-arm, and total fracture using longitudinal data from the Women's Health Initiative Observational Study and Clinical Trials. Secondarily, we evaluated changes in bone mineral density (BMD) and DII scores. DII scores were calculated from baseline food frequency questionnaires (FFQs) completed by 160,191 participants (mean age 63 years) without history of hip fracture at enrollment. Year 3 FFQs were used to calculate a DII change score. Fractures were reported at least annually; hip fractures were confirmed by medical records. Hazard ratios for fractures were computed using multivariable-adjusted Cox proportional hazard models, further stratified by age and race/ethnicity. Pairwise comparisons of changes in hip BMD, measured by dual-energy X-ray absorptiometry from baseline, year 3, and year 6 were analyzed by quartile (Q1 = least inflammatory diet) of baseline DII scores in a subgroup of women (n = 10,290). Mean DII score improved significantly over 3 years (p < 0.01), but change was not associated with fracture risk. Baseline DII score was only associated with hip fracture risk in younger white women (HR Q4,1.48; 95% CI, 1.09 to 2.01; p = 0.01). There were no significant associations among white women older than 63 years or other races/ethnicities. Women with the least inflammatory DII scores had less loss of hip BMD (p = 0.01) by year 6, despite lower baseline hip BMD, versus women with the most inflammatory DII scores. In conclusion, a less inflammatory dietary pattern was associated with less BMD loss in postmenopausal women. A more inflammatory diet was associated with increased hip fracture risk only in white women younger than 63 years. PMID:28019686
Steinberg, Benjamin A; Moghbeli, Nazanin; Buros, Jacqueline; Ruda, Mikhail; Parkhomenko, Alexander; Raju, B Soma; García-Castillo, Armando; Janion, Marianna; Nicolau, José C; Fox, Keith A A; Morrow, David A; Gibson, C Michael; Antman, Elliott M
2007-07-01
Outcomes in patients with ST-elevation myocardial infarction (STEMI) differ between those in clinical trials and those in routine practice, as well as across different regions. We hypothesized that adjustment for baseline risk would minimize such variations. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction (ExTRACT-TIMI) 25 registry was an observational study of patients with STEMI presenting to hospitals participating in the ExTRACT-TIMI 25 randomized clinical trial. Consecutive patients with STEMI who were not enrolled in the trial were entered into the registry. Demographics, in-hospital therapies, and in-hospital events were collected. Baseline risk was assessed using the TIMI Risk Index for STEMI. To adjust for differences among the countries from which the patients presented, the gross national income per annum per capita (GNI) was used. A total of 3726 patients were registered from 109 sites in 25 countries. Patients in the registry had a higher baseline risk than those in the trial; they had more extensive prior cardiac histories and more comorbidities. Unadjusted in-hospital mortality was higher in the registry (8.3%) than in the trial (6.6%) (hazard ratio, 1.30; P < .001); however, after adjusting for TIMI Risk Index, mortality was similar (hazard ratio(adj), 1.00; P = .97). The GNI was not significantly predictive of in-hospital mortality in the multivariable model of the registry. Patients in the registry had higher mortality than those in the trial. This difference could be explained by the higher baseline risk of patients in the registry. After adjusting for baseline risk, the GNI of the country in which the patient presented did not contribute to predicting in-hospital mortality.
Cohn, B A; Wingard, D L; Cohen, R D; Cirillo, P M; Kaplan, G A
1990-03-01
In a previous analysis from the Alameda County Study, it was observed that although men had higher heart disease mortality rates than women, there was no male excess in the prevalence of self-reported heart disease morbidity at baseline or in new reports of morbidity 9 years past baseline. This apparent contradiction might occur because women report less severe heart disease than men. In the present study, this hypothesis was evaluated by examining whether self-reported heart trouble was more strongly associated with subsequent heart disease mortality for men than for women in a representative sample of the population of Alameda County, California, selected in 1965 and followed for mortality for 19 years (n = 3,742). In a time-dependent Cox model, self-reported heart trouble was a stronger predictor of heart disease mortality for men, but only during the early years of follow-up (p = 0.00). This effect was due to a shorter time to death for men who reported heart trouble. The relative hazard for men reporting heart trouble was 6.6 (95% confidence interval (CI) 3.7-11.6) at baseline, declining to 3.2 (95% CI 2.2-4.5) by 5 years past baseline and 1.5 (95% CI 0.9-2.5) by 10 years past baseline. Self-reported heart trouble was a consistent predictor of subsequent heart disease mortality for women over the 19-year follow-up period (relative hazard = 2.0, 95% CI 1.4-2.8). Sex differences in the prognosis of self-reported heart trouble were masked in non-time-dependent analyses. These results illustrate that consideration of time dependence may be required for meaningful analysis of long-term cohort studies. Possible explanations of the shorter time to death for men who reported heart trouble are discussed.
Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.
2015-01-01
Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136. PMID:25681380
Ferré-Huguet, Núria; Nadal, Martí; Schuhmacher, Marta; Domingo, José L
2006-01-01
The purpose of this study was to assess the environmental impact of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the vicinity of a new hazardous waste incinerator (HWI) 4 years after regular operation of the facility. A double approach was carried out. The PCDD/F congener profiles corresponding to environmental samples, soil and herbage, collected before the HWI (baseline) and 4 years after starting regular operations, as well as PCDD/F profiles of air emission samples, were compared. The potential health risks (carcinogenic and noncarcinogenic) due to PCDD/F exposure were assessed for adults and children living in the neighborhood of the facility. Human exposure to PCDD/Fs was mainly due to dietary food intake. Comparisons between the PCDD/F congener profiles corresponding to the baseline and current surveys, as well as data concerning the human health risk assessment, indicate that the HWI in question does not cause additional risks to the environment orto the population living in the vicinity of the facility.
Kabat, Geoffrey C; Cross, Amanda J; Park, Yikyung; Schatzkin, Arthur; Hollenbeck, Albert R; Rohan, Thomas E; Sinha, Rashmi
2009-05-15
A number of studies have reported that intake of red meat or meat cooked at high temperatures is associated with increased risk of breast cancer, but other studies have shown no association. We assessed the association between meat, meat-cooking methods, and meat-mutagen intake and postmenopausal breast cancer in the NIH-AARP Diet and Health Study cohort of 120,755 postmenopausal women who completed a food frequency questionnaire at baseline (1995-1996) as well as a detailed meat-cooking module within 6 months following baseline. During 8 years of follow-up, 3,818 cases of invasive breast cancer were identified in this cohort. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). After adjusting for covariates, intake of total meat, red meat, meat cooked at high temperatures, and meat mutagens showed no association with breast cancer risk. This large prospective study with detailed information on meat preparation methods provides no support for a role of meat mutagens in the development of postmenopausal breast cancer. (c) 2008 Wiley-Liss, Inc.
Gross, Alden L; Rebok, George W; Unverzagt, Frederick W; Willis, Sherry L; Brandt, Jason
2011-09-01
The present study sought to predict changes in everyday functioning using cognitive tests. Data from the Advanced Cognitive Training for Independent and Vital Elderly trial were used to examine the extent to which competence in different cognitive domains--memory, inductive reasoning, processing speed, and global mental status--predicts prospectively measured everyday functioning among older adults. Coefficients of determination for baseline levels and trajectories of everyday functioning were estimated using parallel process latent growth models. Each cognitive domain independently predicts a significant proportion of the variance in baseline and trajectory change of everyday functioning, with inductive reasoning explaining the most variance (R2 = .175) in baseline functioning and memory explaining the most variance (R2 = .057) in changes in everyday functioning. Inductive reasoning is an important determinant of current everyday functioning in community-dwelling older adults, suggesting that successful performance in daily tasks is critically dependent on executive cognitive function. On the other hand, baseline memory function is more important in determining change over time in everyday functioning, suggesting that some participants with low baseline memory function may reflect a subgroup with incipient progressive neurologic disease.
Reversing the sequence: reducing alcohol consumption by overcoming alcohol attentional bias.
Fadardi, Javad Salehi; Cox, W Miles
2009-05-01
The aims of the research were to (a) compare the alcohol attentional bias (AAB) of social, hazardous, and harmful drinkers and (b) assess the effects of alcohol attention-control training on the AAB and alcohol consumption of hazardous and harmful drinkers. Participants were social drinkers (N=40), hazardous drinkers (N=89), and harmful drinkers (N=92). Paper-and-pencil measures were used to collect information about participants' socio-demographic characteristics, health status, motivational structure, drinking-related locus of control and situational self-confidence, readiness to change, affect, and alcohol consumption. Computerized classic, alcohol- and concerns-Stroop tests were administered. All participants were tested individually, with the order of tests counterbalanced across participants. After the baseline assessment, the hazardous and harmful drinkers were trained with the Alcohol Attention-Control Training Program (AACTP) for two and four sessions, respectively. Both samples completed a post-training assessment, and the harmful drinkers also completed 3-month follow-up. Results indicated that (a) the harmful drinkers had larger AAB than the hazardous and the social drinkers; (b) the attentional training reduced the hazardous and harmful drinkers' AAB; and (c) the harmful drinkers showed post-training reductions in alcohol consumption and improvements on the other drinking-related indices. The harmful drinkers' improvements were maintained at the 3-month follow-up.
Gaggin, Hanna K; Belcher, Arianna M; Gandhi, Parul U; Ibrahim, Nasrien E; Januzzi, James L
2016-12-01
Little is known regarding objective predictors of cachexia affecting patients with heart failure (HF). We studied 108 stable chronic systolic HF patients with serial echocardiography and biomarker measurements over 10 months. Cachexia was defined as weight loss ≥5 % from baseline or final BMI <20 kg/m 2 ; 18.5 % developed cachexia. While there were no significant differences in baseline or serial echocardiographic measures in those developing cachexia, we found significant differences in baseline amino-terminal pro-B type natriuretic peptide (NT-proBNP), highly sensitive troponin I, sST2, and endothelin-1. Baseline log NT-proBNP (hazard ratio (HR) = 2.57, p = 0.004) and edema (HR = 3.36, p = 0.04) were predictive of cachexia in an adjusted analysis. When serial measurement of biomarkers was considered, only percent time with NT-proBNP ≥1000 pg/mL was predictive of cachexia. Thus, a close association exists between baseline and serial measurement of NT-proBNP and HF cachexia.
Lunar mission safety and rescue: Hazards analysis and safety requirements
NASA Technical Reports Server (NTRS)
1971-01-01
The results are presented of the hazards analysis which was concerned only with hazards to personnel and not with loss of equipment or property. Hazards characterization includes the definition of a hazard, the hazard levels, and the hazard groups. The analysis methodology is described in detail. The methodology was used to prepare the top level functional flow diagrams, to perform the first level hazards assessment, and to develop a list of conditions and situations requiring individual hazard studies. The 39 individual hazard study results are presented in total.
Longitudinal Change of Self-Perceptions of Aging and Mortality
2014-01-01
Objective. To understand the association between self-perceptions of aging (SPA) and mortality in late life. Method. The sample (n = 1,507) was drawn from the Australian Longitudinal Study of Aging (baseline age = 65–103 years). We used joint growth curve and survival models on 5 waves of data for a period of 16 years to investigate the random intercept and slope of SPA for predicting all-cause mortality. Results. The unadjusted model revealed that poor SPA at baseline, as well as decline in SPA, increased the risk of mortality (SPA intercept hazard ratio [HR] = 1.21, 95% confidence interval [CI] = 1.13, 1.31; SPA slope HR = 1.17, 95% CI = 1.02, 1.33). This relationship remained significant for the SPA intercept after adjusting for other risk factors including demographics, physical health, cognitive functioning, and well-being. Conclusion. These findings suggest that a single measurement of SPA in late life may be very informative of future long-term vulnerability to health decline and mortality. Furthermore, a dynamic measure of SPA may be indicative of adaptation to age-related changes. This supports a “self-fulfilling” hypothesis, whereby SPA is a lens through which age-related changes are interpreted, and these interpretations can affect future health and health behaviors. PMID:23419867
Kidney stones and kidney function loss: a cohort study.
Alexander, R Todd; Hemmelgarn, Brenda R; Wiebe, Natasha; Bello, Aminu; Morgan, Catherine; Samuel, Susan; Klarenbach, Scott W; Curhan, Gary C; Tonelli, Marcello
2012-08-29
To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. Alberta, Canada, between 1997 and 2009. 3,089,194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1,954,836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. One or more kidney stones during follow-up. Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m(2)), and sustained doubling of serum creatinine concentration from baseline. 23,706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68,525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥ 50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms.
Sherrouse, Benson C.; Hester, David J.
2008-01-01
The Multi-Hazards Demonstration Project (MHDP) is a collaboration between the U.S. Geological Survey (USGS) and various partners from the public and private sectors and academia, meant to improve Southern California's resiliency to natural hazards. In support of the MHDP objectives, the ShakeOut Scenario was developed. It describes a magnitude 7.8 earthquake along the southernmost 300 kilometers (200 miles) of the San Andreas Fault, identified by geoscientists as a plausible event that will cause moderate to strong shaking over much of the eight-county (Imperial, Kern, Los Angeles, Orange, Riverside, San Bernardino, San Diego, and Ventura) Southern California region. This report uses historical, estimated, and projected population data from several Federal and State data sources to estimate baseline characteristics and trends of the region's population migration (that is, changes in a person's place of residence over time). The analysis characterizes migration by various demographic, economic, family, and household variables for the period 1995-2000. It also uses existing estimates (beginning in 2001) of the three components of population change - births, deaths, and migration - to extrapolate near-term projections of county-level migration trends through 2010. The 2010 date was chosen to provide baseline projections corresponding to a two-year recovery period following the November 2008 date that was selected for the occurrence of the ShakeOut Scenario earthquake. The baseline characteristics and projections shall assist with evaluating the effects of inflow and outflow migration trends for alternative futures in which the simulated M7.8 earthquake either does or does not occur and the impact of the event on housing and jobs, as well as community composition and regional economy changes based on dispersion of intellectual, physical, economic, and cultural capital.
Behrens, Thomas; Rabstein, Sylvia; Wichert, Katharina; Erbel, Raimund; Eisele, Lewin; Arendt, Marina; Dragano, Nico; Brüning, Thomas; Jöckel, Karl-Heinz
2017-11-01
Objectives We investigated the association of shift and night work with the incidence of prostate cancer using data of the population-based prospective Heinz Nixdorf Recall Study from the highly industrialized Ruhr area in Germany. Methods Participants of the baseline survey were recruited between 2000-2003. A follow-up survey including, a detailed interview on shift and night work, was conducted from 2011-2014. We included 1757 men who did not report a history of prostate cancer at baseline. We assessed shift- and night-work exposure up to time of the baseline interview. Incident prostate cancers were recorded from baseline through September 2014. We calculated hazard ratios (HR) of shift- and night-work exposure using Cox proportional hazards regression with age at event as timescale, adjusting for smoking status, family history of prostate cancer, education (≤13, 14-17, ≥18 years), and equivalent income (low, medium, high). Results We observed a twofold increased HR for prostate cancer among shift and night workers. Ever employment in shift work was associated with HR 2.29, 95% confidence interval (CI) 1.43-3.67 and night work with HR 2.27, 95% CI 1.42-3.64. HR increased steadily with duration of employment in shift or night work. Stratifying analyses by preferred midpoint of sleep, yielded strongly elevated HR among subjects with early sleep preference, although these analyses were limited by small number of cases. Conclusions We identified increased risks for prostate cancer among men with employment in shift or night work. HR were strongly elevated among long-term employed shift workers and men with early preferred midpoint of sleep.
Westerdahl, Christina; Zöller, Bengt; Arslan, Eren; Erdine, Serap; Nilsson, Peter M
2014-12-01
Screening of hypertension has been advocated for early detection and treatment. Severe hypertension (grade 3 hypertension) is a strong predictor for cardiovascular disease. This study aimed to evaluate not only the risk factors for developing severe hypertension, but also the prospective morbidity and mortality risk associated with severe hypertension in a population-based screening and intervention programme. In all, 18,200 individuals from a population-based cohort underwent a baseline examination in 1972-1992 and were re-examined in 2002-2006 in Malmö, Sweden. In total, 300 (1.6%) patients with severe hypertension were identified at re-examination, and predictive risk factors from baseline were calculated. Total and cause-specific morbidity and mortality were followed in national registers in all severe hypertension patients, as well as in age and sex-matched normotensive controls. Cox analyses for hazard ratios were used. Men developing severe hypertension differed from matched controls in baseline variables associated with the metabolic syndrome, as well as paternal history of hypertension (P < 0.001). Women with later severe hypertension were characterized by elevated BMI and a positive maternal history for hypertension at baseline. The risk of mortality, coronary events, stroke and diabetes during follow-up was higher among severe hypertension patients compared to controls. For coronary events, the risk remained elevated adjusted for other risk factors [hazard ratio 2.31, 95% confidence interval (CI) 1.22-4.40, P = 0.011]. Family history and variables associated with metabolic syndrome are predictors for severe hypertension after a long-term follow-up. Severe hypertension is associated with increased mortality, cardiovascular morbidity and incident diabetes in spite of treatment. This calls for improved risk factor control in patients with severe hypertension.
Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong
2018-01-01
We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.
Duration of diabetes and risk of ischemic stroke: the Northern Manhattan Study.
Banerjee, Chirantan; Moon, Yeseon P; Paik, Myunghee C; Rundek, Tatjana; Mora-McLaughlin, Consuelo; Vieira, Julio R; Sacco, Ralph L; Elkind, Mitchell S V
2012-05-01
Diabetes increases stroke risk, but whether diabetes status immediately before stroke improves prediction and whether duration is important are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. Among 3298 stroke-free participants in the Northern Manhattan Study, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median, 9 years). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors. Mean age was 69 ± 10 years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and 10% had development of diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR, 2.5; 95% CI, 1.9-3.3) and diabetes considered as a time-dependent covariate (HR, 2.4; 95% CI, 1.8-3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR, 1.03 per year with diabetes; 95% CI, 1.02-1.04). Compared to nondiabetic participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1-2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1-3.0), and ≥ 10 years (adjusted HR, 3.2; 95% CI, 2.4-4.5) were at increased risk. Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥ 10 years.
Mortamais, Marion; Abdennour, Meriem; Bergua, Valérie; Tzourio, Christophe; Berr, Claudine; Gabelle, Audrey; Akbaraly, Tasnime N.
2018-01-01
Background: Anxiety is common in patients with cognitive impairment and dementia. However, whether anxiety is a risk factor for dementia is still not known. We aimed to examine the association between trait anxiety at baseline and the 10-year risk of incident dementia to determine to which extent depressive symptoms influence this relationship in the general population. Methods: Data came from 5,234 community-dwelling participants from the Three-City prospective cohort study, aged 65 years at baseline and followed over 10 years. At baseline, anxiety trait was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), and depressive symptoms using Center for Epidemiologic Studies-Depression Scale (CESD). Use of anxiolytic drugs was also considered. Diagnoses of dementia were made at baseline and every 2 years. To examine the relationship between anxiety exposures and risk of incident dementia, Cox proportional hazard regression models were performed. Results: Taking anxiolytic drugs or having high trait anxiety (STAI score ≥ 44) increased the risk of dementia assessed over 10 years of follow-up [Hazard Ratio (HR) = 1.39, 95%CI: 1.08–1.80, p = 0.01 and HR = 1.26, 95%CI: 1.01–1.57, p = 0.04, respectively], independently of a large panel of socio-demographic variables, health behaviors, cardio-metabolic disorders, and additional age-related disorders such as cardiovascular diseases, activity limitations, and cognitive deficit. However, the associations were substantially attenuated after further adjustment for depressive symptoms. Conclusion: Our findings suggest that depressive symptoms shape the association between anxiety trait and dementia. Further research is needed to replicate our findings and extrapolate our results to anxiety disorders. PMID:29719498
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peek, Dennis W.
The approach was to perform a document search, supplemented by a visual site inspection, to identify potential environmental contamination associated with the property. Factors evaluated included hazardous substances; petroleum products and derivatives; environmental restoration sites; areas of concern; storage tanks; oil/water separators; grease traps; wash racks; waste tanks; pesticides; military munitions/ordnance; medical or bio-hazardous waste; radioactive waste; solid/municipal waste; indoor air quality; groundwater; wastewater treatment, collection, and disposal/discharge; drinking water quality; utilities; asbestos; polychlorinated biphenyls (PCBs); radon; lead-based paint; cultural resources; floodplains; and natural/biological resources.
Gooding, Holly C; Shay, Christina M; Ning, Hongyan; Gillman, Matthew W; Chiuve, Stephanie E; Reis, Jared P; Allen, Norrina B; Lloyd-Jones, Donald M
2015-10-29
Middle-aged adults with ideal blood pressure, cholesterol, and glucose levels exhibit substantially lower cardiovascular mortality than those with unfavorable levels. Four healthy lifestyle components-optimal body weight, diet, physical activity, and not smoking-are recommended for cardiovascular health (CVH). This study quantified associations between combinations of healthy lifestyle components measured in young adulthood and loss of the ideal CVH profile into middle age. Analyses included 2164 young adults in the Coronary Artery Risk Development in Young Adults study with the ideal CVH profile (defined as untreated blood pressure <120/80 mm Hg, total cholesterol <200 mg/dL, fasting blood glucose <100 mg/dL, and absence of cardiovascular disease) at baseline. Cox proportional hazards regression models estimated hazard ratios for loss of the ideal CVH profile over 25 years according to 4 individual and 16 combinations of optimal healthy lifestyle components measured in young adulthood: body mass index, physical activity, nonsmoking status, and diet quality. Models were adjusted for age, sex, race, education, study center, and baseline blood pressure, cholesterol, and glucose. Eighty percent (n=1737) of participants lost the ideal CVH profile by middle age; loss was greatest for young adults with no optimal healthy lifestyle components at baseline. Relative to young adults with no optimal healthy lifestyle components, those with all 4 were less likely to lose the ideal CVH profile (hazard ratio 0.59, 95% CI 0.44-0.80). Combinations that included optimal body mass index and nonsmoking status were each associated with lower risk. Optimal body mass index and not smoking in young adulthood were protective against loss of the ideal CVH profile through middle age. Importance of diet and physical activity may be included through their effects on healthy weight. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Gunderson, Erica P; Hurston, Shanta R; Ning, Xian; Lo, Joan C; Crites, Yvonne; Walton, David; Dewey, Kathryn G; Azevedo, Robert A; Young, Stephen; Fox, Gary; Elmasian, Cathie C; Salvador, Nora; Lum, Michael; Sternfeld, Barbara; Quesenberry, Charles P
2015-12-15
Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain. To evaluate lactation and the 2-year incidence of DM after GDM pregnancy. Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030). Integrated health care system. 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011. Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders. Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios. Randomized design is not feasible or desirable for clinical studies of lactation. Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery. National Institute of Child Health and Human Development.
Lipid Profile Components and Risk of Ischemic Stroke
Willey, Joshua Z.; Xu, Qiang; Boden-Albala, Bernadette; Paik, Myunghee C.; Moon, Yeseon Park; Sacco, Ralph L.; Elkind, Mitchell S. V.
2010-01-01
Objective To explore the relationship between lipid profile components and incident ischemic stroke in a stroke-free prospective cohort. Design Population-based prospective cohort study. Setting Northern Manhattan, New York. Patients Stroke-free community residents. Intervention As part of the Northern Manhattan Study, baseline fasting blood samples were collected on stroke-free community residents followed up for a mean of 7.5 years. Main Outcome Measures Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for lipid profile components and ischemic stroke after adjusting for demographic and risk factors. In secondary analyses, we used repeated lipid measures over 5 years from a 10% sample of the population to calculate the change per year of each of the lipid parameters and to impute time-dependent lipid parameters for the full cohort. Results After excluding those with a history of myocardial infarction, 2940 participants were available for analysis. Baseline high-density lipoprotein cholesterol, triglyceride, and total cholesterol levels were not associated with risk of ischemic stroke. Low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol levels were associated with a paradoxical reduction in risk of stroke. There was an interaction with use of cholesterol-lowering medication on follow-up, such that LDL-C level was only associated with a reduction in stroke risk among those taking medications. An LDL-C level greater than 130 mg/dL as a time-dependent covariate showed an increased risk of ischemic stroke (adjusted hazard ratio, 3.81; 95% confidence interval, 1.53–9.51). Conclusions Baseline lipid panel components were not associated with an increased stroke risk in this cohort. Treatment with cholesterol-lowering medications and changes in LDL-C level over time may have attenuated the risk in this population, and lipid measurements at several points may be a better marker of stroke risk. PMID:19901173
Landslide Hazard Zonation and Risk Assessment of Ramganga Basin in Garhwal Himalaya
NASA Astrophysics Data System (ADS)
Wasini Pandey, Bindhy; Roy, Nikhil
2016-04-01
The Himalaya being unique in its physiographic, tectonic and climatic characteristics coupled with many natural and man-made factors is inherently prone to landslides. These landslides lead to mass loss of property and lives every year in Himalayas. Hence, Landslide Hazard Zonation is important to take quick and safe mitigation measures and make strategic planning for future development. The present study tries to explore the causes of landslides in Ramganga Basin in Garhwal Himalaya, which has an established history and inherent susceptibility to massive landslides has been chosen for landslide hazard zonation and risk assessment. The satellite imageries of LANDSAT, IRS P6, ASTER along with Survey of India (SOI) topographical sheets formed the basis for deriving baseline information on various parameters like slope, aspect, relative relief, drainage density, geology/lithology and land use/land cover. The weighted parametric method will be used to determine the degree of susceptibility to landslides. Finally, a risk map will be prepared from the landslide probability values, which will be classified into no risk, very low to moderate, high, and very high to severe landslide hazard risk zones. Keywords: Landslides, Hazard Zonation, Risk Assessment
Goveas, Joseph S; Espeland, Mark A; Woods, Nancy F; Wassertheil-Smoller, Sylvia; Kotchen, Jane M
2011-01-01
To examine whether significant depressive symptoms in postmenopausal women increases the risk of subsequent mild cognitive impairment (MCI) and dementia. Prospective cohort study. Thirty nine of the 40 Women's Health Initiative (WHI) clinical centers that participated in a randomized clinical trial of hormone therapy. Six thousand three hundred seventy-six postmenopausal women without cognitive impairment aged 65 to 79 at baseline. Depressive disorders were assessed using an eight-item Burnam algorithm and followed annually for a mean period of 5.4 years. A central adjudication committee classified the presence of MCI and probable dementia based on an extensive neuropsychiatric examination. Eight percent of postmenopausal women in this sample reported depressive symptoms above a 0.06 cut point on the Burnam algorithm. Depressive disorder at baseline was associated with greater risk of incident MCI (hazard ratio (HR)=1.98, 95% confidence interval (CI)=1.33-2.94), probable dementia (HR=2.03, 95% CI=1.15-3.60), and MCI or probable dementia (HR=1.92, 95% CI=1.35-2.73) after controlling for sociodemographic characteristics, lifestyle and vascular risk factors, cardiovascular and cerebrovascular disease, antidepressant use, and current and past hormone therapy status. Assignment to hormone therapy and baseline cognitive function did not affect these relationships. Women without depression who endorsed a remote history of depression had a higher risk of developing dementia. Clinically significant depressive symptoms in women aged 65 and older are independently associated with greater incidence of MCI and probable dementia. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.
Markus, Hugh S; King, Alice; Shipley, Martin; Topakian, Raffi; Cullinane, Marisa; Reihill, Sheila; Bornstein, Natan M; Schaafsma, Arjen
2010-01-01
Summary Background Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis. Methods The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity. Findings 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results. Interpretation Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy. Funding British Heart Foundation. PMID:20554250
DOE Office of Scientific and Technical Information (OSTI.GOV)
King, David A.
2012-11-29
This environmental baseline survey (EBS) report documents the baseline environmental conditions of five land parcels located near the U.S. Department of Energy?s (DOE?s) East Tennessee Technology Park (ETTP), including West Black Oak Ridge, East Black Oak Ridge, McKinney Ridge, West Pine Ridge, and Parcel 21d. Preparation of this report included the detailed search of federal government records, title documents, aerial photos that may reflect prior uses, and visual inspections of the property and adjacent properties. Interviews with current employees involved in, or familiar with, operations on the real property were also conducted to identify any areas on the property wheremore » hazardous substances and petroleum products, or their derivatives, and acutely hazardous wastes may have been released or disposed. In addition, a search was made of reasonably obtainable federal, state, and local government records of each adjacent facility where there has been a release of any hazardous substance or any petroleum product or their derivatives, including aviation fuel and motor oil, and which is likely to cause or contribute to a release of any hazardous substance or any petroleum product or its derivatives, including aviation fuel or motor oil, on the real property. A radiological survey and soil/sediment sampling was conducted to assess baseline conditions of Parcel 21d that were not addressed by the soils-only no-further-investigation (NFI) reports. Groundwater sampling was also conducted to support a Parcel 21d decision. Based on available data West Black Oak Ridge, East Black Oak Ridge, McKinney Ridge, and West Pine Ridge are not impacted by site operations and are not subject to actions per the Federal Facility Agreement (FFA). This determination is supported by visual inspections, records searches and interviews, groundwater conceptual modeling, approved NFI reports, analytical data, and risk analysis results. Parcel 21d data, however, demonstrate impacts from site operations, specifically as associated with lead in surface soil at the abandoned water tank and nickel in surface soils over the northern portion of the parcel from former Bldg. K-1037 smelting operations. Low level detections of organics are also reported in some surface soils including Polycyclic aromatic hydrocarbons (PAHs) near Blair Road and common laboratory contaminants at randomly distributed locations. However, human health risk from site-related contaminants of potential concern (COPCs) are acceptable?though maximum concentrations of lead and nickel and the screening-level ecological risk assessment (SLERA) demonstrate no further ecological evaluation is warranted. The weight of evidence leads to the conclusion Parcel 21d does not require any actions per the FFA.« less
2009-01-01
Background During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia. PMID:19331670
Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis
Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano
2017-01-01
Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs –7.31 [6.23]; P = .04). Conclusions and Relevance These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001. PMID:28384752
Saulnier, Pierre-Jean; Wheelock, Kevin M; Howell, Scott; Weil, E Jennifer; Tanamas, Stephanie K; Knowler, William C; Lemley, Kevin V; Mauer, Michael; Yee, Berne; Nelson, Robert G; Beisswenger, Paul J
2016-12-01
We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA 1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08-2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02-1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = -0.26, P = 0.01; and partial r = -0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. © 2016 by the American Diabetes Association.
Saulnier, Pierre-Jean; Wheelock, Kevin M.; Howell, Scott; Weil, E. Jennifer; Tanamas, Stephanie K.; Knowler, William C.; Lemley, Kevin V.; Mauer, Michael; Yee, Berne; Beisswenger, Paul J.
2016-01-01
We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded. Glomerular filtration rate (GFR) was measured annually. Kidney biopsies were performed at the end of the trial. Five AGEs were measured in serum collected at enrollment and at kidney biopsy. RFL was defined as ≥40% decline of measured GFR from baseline. Of 168 participants (mean baseline age 41 years, HbA1c 9.2%, GFR 164 mL/min, and albumin-to-creatinine ratio 31 mg/g), 104 reached the RFL end point during median follow-up of 8.0 years. After multivariable adjustment, each doubling of carboxyethyl lysine (hazard ratio [HR] 1.60 [95% CI 1.08–2.37]) or methylglyoxal hydroimidazolone (HR 1.30 [95% CI 1.02–1.65]) concentration was associated with RFL. Carboxyethyl lysine, carboxymethyl lysine, and methylglyoxal hydroimidazolone correlated positively with cortical interstitial fractional volume (partial r = 0.23, P = 0.03; partial r = 0.25, P = 0.02; and partial r = 0.31, P = 0.003, respectively). Glyoxyl hydroimidazolone and methylglyoxal hydroimidazolone correlated negatively with total filtration surface per glomerulus (partial r = −0.26, P = 0.01; and partial r = −0.21, P = 0.046, respectively). AGEs improve prediction of RFL and its major structural correlates. PMID:27609106
Kim, Jae-Min; Stewart, Robert; Bae, Kyung-Yeol; Yang, Su-Jin; Yoon, Jin-Sang; Jung, Sung-Won; Lee, Min-Soo; Yim, Hyeon-Woo; Jun, Tae-Youn
2011-11-01
Physical and depressive disorders frequently co-occur, but effects of physical health on depression treatment outcomes have received little research. This study aimed to compare treatment outcomes between people with depressive disorder with and without comorbid physical disorders. A Korean nationwide sample of 723 people with depressive disorder initiated on antidepressant treatment, and re-evaluated at 1, 2, 4, 8, and 12 weeks later. Assessment scales for evaluating depressive symptoms (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and every follow-up visit. Achievement of remission or response was defined only when these were maintained to the 12 weeks study endpoint or to the last follow-up examination, if earlier, with the date of the first observed remission point applied as the timing of remission. Logistic regression and Cox proportional hazards models were used. Of the sample, 247 (34%) had at least one physical disorder. This was associated with lower socioeconomic status and more severe depressive symptoms at baseline, but was not associated with any treatment related characteristics including antidepressant type and regimen, concomitant medications, side effects, and duration of treatment period. After adjustment, patients with physical comorbidity responded more slowly and less often - particularly in domains of anxiety, global severity, and functioning (all p-values <.005). More intensive assessment and integrated treatment approaches are needed to facilitate treatment responses for depressive disorders in people with physical comorbidity. Future comparative studies between conventional and integrated treatment approaches are indicated for depressive disorders with physical comorbidity. 2011 Elsevier Inc. All rights reserved.
Tank waste remediation system functions and requirements document
DOE Office of Scientific and Technical Information (OSTI.GOV)
Carpenter, K.E
1996-10-03
This is the Tank Waste Remediation System (TWRS) Functions and Requirements Document derived from the TWRS Technical Baseline. The document consists of several text sections that provide the purpose, scope, background information, and an explanation of how this document assists the application of Systems Engineering to the TWRS. The primary functions identified in the TWRS Functions and Requirements Document are identified in Figure 4.1 (Section 4.0) Currently, this document is part of the overall effort to develop the TWRS Functional Requirements Baseline, and contains the functions and requirements needed to properly define the top three TWRS function levels. TWRS Technicalmore » Baseline information (RDD-100 database) included in the appendices of the attached document contain the TWRS functions, requirements, and architecture necessary to define the TWRS Functional Requirements Baseline. Document organization and user directions are provided in the introductory text. This document will continue to be modified during the TWRS life-cycle.« less
A new estimator for VLBI baseline length repeatability
NASA Astrophysics Data System (ADS)
Titov, O.
2009-11-01
The goal of this paper is to introduce a more effective technique to approximate for the “repeatability-baseline length” relationship that is used to evaluate the quality of geodetic VLBI results. Traditionally, this relationship is approximated by a quadratic function of baseline length over all baselines. The new model incorporates the mean number of observed group delays of the reference radio sources (i.e. estimated as global parameters) used in the estimation of each baseline. It is shown that the new method provides a better approximation of the “repeatability-baseline length” relationship than the traditional model. Further development of the new approach comes down to modeling the repeatability as a function of two parameters: baseline length and baseline slewing rate. Within the framework of this new approach the station vertical and horizontal uncertainties can be treated as a function of baseline length. While the previous relationship indicated that the station vertical uncertainties are generally 4-5 times larger than the horizontal uncertainties, the vertical uncertainties as determined by the new method are only larger by a factor of 1.44 over all baseline lengths.
Vidal-Petiot, Emmanuelle; Stebbins, Amanda; Chiswell, Karen; Ardissino, Diego; Aylward, Philip E; Cannon, Christopher P; Ramos Corrales, Marco A; Held, Claes; López-Sendón, José Luis; Stewart, Ralph A H; Wallentin, Lars; White, Harvey D; Steg, Philippe Gabriel
2017-10-01
To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
2013-01-01
Background Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated. Methods This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (≥2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI. Results Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake. Conclusion These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use. PMID:23635086
Bariatric surgery is associated with improvement in kidney outcomes.
Chang, Alex R; Chen, Yuan; Still, Christopher; Wood, G Craig; Kirchner, H Lester; Lewis, Meredith; Kramer, Holly; Hartle, James E; Carey, David; Appel, Lawrence J; Grams, Morgan E
2016-07-01
Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Long, Thorir E; Sigurdsson, Martin I; Sigurdsson, Gisli H; Indridason, Olafur S
2016-12-01
Acute kidney injury (AKI) is a common complication of medical and surgical interventions in hospitalized patients and associates with high mortality. Our aim was to examine renal recovery and long-term survival and time trends in AKI survival. Changes in serum creatinine (SCr) were used to define AKI in patients at Landspitali University Hospital in Iceland from 1993 to 2013. Renal recovery was defined as SCr < 1.5× baseline. Out of 25 274 individuals who had their highest measured SCr during hospitalization and an available baseline SCr, 10,419 (41%) had AKI during hospitalization (H-AKI), 19%, 11% and 12% with Stage 1, 2 and 3, respectively. The incidence of H-AKI increased from 18.6 (95% CI, 14.7-22.5) to 29.9 (95% CI, 26.7-33.1) per 1000 admissions/year over the study period. Survival after H-AKI was 61% at 90-days and 51% at one year. Comparing H-AKI patients to propensity score matched individuals the hazard ratio for death was 1.49 (1.36-1.62), 2.17 (1.95-2.41) and 2.95 (2.65-3.29) for Stage 1, 2 and 3, respectively. One-year survival of H-AKI patients improved from 47% in 1993-1997 to 57% in 2008-2013 and the adjusted hazard ratio for mortality improved, compared to the first 5-year period, 0.85 (0.81-0.89), 0.67 (0.64-0.71), and 0.57 (0.53-0.60) for each subsequent 5-year interval. Recovery of renal function was achieved in 88%, 58% and 44% of patients in Stages 1, 2 and 3, respectively, improving with time. Acute kidney injury is an independent predictor of long-term mortality in hospitalized patients but there has been a marked improvement in survival and renal recovery over the past two decades. © 2015 Asian Pacific Society of Nephrology.
2012-01-01
Introduction There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. Methods This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). Results Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). Conclusion We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear. PMID:22906142
McAdams-DeMarco, Mara A; Maynard, Janet W; Coresh, Josef; Baer, Alan N
2012-08-20
There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear.
Biological age as a useful index to predict seventeen-year survival and mortality in Koreans.
Yoo, Jinho; Kim, Yangseok; Cho, Eo Rin; Jee, Sun Ha
2017-01-05
Many studies have been conducted to quantitatively estimate biological age using measurable biomarkers. Biological age should function as a valid proxy for aging, which is closely related with future work ability, frailty, physical fitness, and/or mortality. A validation study using cohort data found biological age to be a superior index for disease-related mortality than chronological age. The purpose of this study is to demonstrate the validity of biological age as a useful index to predict a person's risk of death in the future. The data consists of 13,106 cases of death from 557,940 Koreans at 20-93 years old, surveyed from 1994 to 2011. Biological ages were computed using 15 biomarkers measured in general health check-ups using an algorithm based on principal component analysis. The influence of biological age on future mortality was analyzed using Cox proportional hazards regression considering gender, chronological age, and event type. In the living subjects, the average biological age was almost the same as the average chronological age. In the deceased, the biological age was larger than the chronological age: largest increment of biological age over chronological age was observed when their baseline chronological age was within 50-59 years. The death rate significantly increased as biological age became larger than chronological age (linear trend test, p value < 0.0001). The largest hazard ratio was observed in subjects whose baseline chronological age was within 50-59 years when the cause was death from non-cancerous diseases (HR = 1.30, 95% confidence intervals = 1.26 - 1.34). The survival probability, over the 17 year term of the study, was significantly decreased in the people whose biological age was larger than chronological age (log rank test, p value < 0.001). Biological age could be used to predict future risk of death, and its effect size varied according to gender, chronological age, and cause of death.
Dunlop, Dorothy D; Song, Jing; Semanik, Pamela A; Sharma, Leena; Bathon, Joan M; Eaton, Charles B; Hochberg, Marc C; Jackson, Rebecca D; Kwoh, C Kent; Mysiw, W Jerry; Nevitt, Michael C; Chang, Rowland W
2014-04-29
To investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression. Prospective multisite cohort study from September 2008 to December 2012. Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA. Disability onset cohort of 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis; the disability progression cohort included 1814 adults. Physical activity was measured by accelerometer monitoring. Disability was ascertained from limitations in instrumental and basic activities of daily living at baseline and two years. The primary outcome was incident disability. The secondary outcome was progression of disability defined by a more severe level (no limitations, limitations to instrumental activities only, 1-2 basic activities, or ≥3 basic activities) at two years compared with baseline. Greater time spent in light intensity activities had a significant inverse association with incident disability. Less incident disability and less disability progression were each significantly related to increasing quartile categories of daily time spent in light intensity physical activities (hazard ratios for disability onset 1.00, 0.62, 0.47, and 0.58, P for trend=0.007; hazard ratios for progression 1.00, 0.59, 0.50, and 0.53, P for trend=0.003) with control for socioeconomic factors (age, sex, race/ethnicity, education, income) and health factors (comorbidities, depressive symptoms, obesity, smoking, lower extremity pain and function, and knee assessments: osteoarthritis severity, pain, symptoms, prior injury). This finding was independent of time spent in moderate-vigorous activities. These prospective data showed an association between greater daily time spent in light intensity physical activities and reduced risk of onset and progression of disability in adults with osteoarthritis of the knee or risk factors for knee osteoarthritis. An increase in daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased.
Hazard function theory for nonstationary natural hazards
NASA Astrophysics Data System (ADS)
Read, L. K.; Vogel, R. M.
2015-11-01
Impact from natural hazards is a shared global problem that causes tremendous loss of life and property, economic cost, and damage to the environment. Increasingly, many natural processes show evidence of nonstationary behavior including wind speeds, landslides, wildfires, precipitation, streamflow, sea levels, and earthquakes. Traditional probabilistic analysis of natural hazards based on peaks over threshold (POT) generally assumes stationarity in the magnitudes and arrivals of events, i.e. that the probability of exceedance of some critical event is constant through time. Given increasing evidence of trends in natural hazards, new methods are needed to characterize their probabilistic behavior. The well-developed field of hazard function analysis (HFA) is ideally suited to this problem because its primary goal is to describe changes in the exceedance probability of an event over time. HFA is widely used in medicine, manufacturing, actuarial statistics, reliability engineering, economics, and elsewhere. HFA provides a rich theory to relate the natural hazard event series (X) with its failure time series (T), enabling computation of corresponding average return periods, risk and reliabilities associated with nonstationary event series. This work investigates the suitability of HFA to characterize nonstationary natural hazards whose POT magnitudes are assumed to follow the widely applied Generalized Pareto (GP) model. We derive the hazard function for this case and demonstrate how metrics such as reliability and average return period are impacted by nonstationarity and discuss the implications for planning and design. Our theoretical analysis linking hazard event series X, with corresponding failure time series T, should have application to a wide class of natural hazards with rich opportunities for future extensions.
Hazard function theory for nonstationary natural hazards
NASA Astrophysics Data System (ADS)
Read, Laura K.; Vogel, Richard M.
2016-04-01
Impact from natural hazards is a shared global problem that causes tremendous loss of life and property, economic cost, and damage to the environment. Increasingly, many natural processes show evidence of nonstationary behavior including wind speeds, landslides, wildfires, precipitation, streamflow, sea levels, and earthquakes. Traditional probabilistic analysis of natural hazards based on peaks over threshold (POT) generally assumes stationarity in the magnitudes and arrivals of events, i.e., that the probability of exceedance of some critical event is constant through time. Given increasing evidence of trends in natural hazards, new methods are needed to characterize their probabilistic behavior. The well-developed field of hazard function analysis (HFA) is ideally suited to this problem because its primary goal is to describe changes in the exceedance probability of an event over time. HFA is widely used in medicine, manufacturing, actuarial statistics, reliability engineering, economics, and elsewhere. HFA provides a rich theory to relate the natural hazard event series (X) with its failure time series (T), enabling computation of corresponding average return periods, risk, and reliabilities associated with nonstationary event series. This work investigates the suitability of HFA to characterize nonstationary natural hazards whose POT magnitudes are assumed to follow the widely applied generalized Pareto model. We derive the hazard function for this case and demonstrate how metrics such as reliability and average return period are impacted by nonstationarity and discuss the implications for planning and design. Our theoretical analysis linking hazard random variable X with corresponding failure time series T should have application to a wide class of natural hazards with opportunities for future extensions.
Interval Estimation of Seismic Hazard Parameters
NASA Astrophysics Data System (ADS)
Orlecka-Sikora, Beata; Lasocki, Stanislaw
2017-03-01
The paper considers Poisson temporal occurrence of earthquakes and presents a way to integrate uncertainties of the estimates of mean activity rate and magnitude cumulative distribution function in the interval estimation of the most widely used seismic hazard functions, such as the exceedance probability and the mean return period. The proposed algorithm can be used either when the Gutenberg-Richter model of magnitude distribution is accepted or when the nonparametric estimation is in use. When the Gutenberg-Richter model of magnitude distribution is used the interval estimation of its parameters is based on the asymptotic normality of the maximum likelihood estimator. When the nonparametric kernel estimation of magnitude distribution is used, we propose the iterated bias corrected and accelerated method for interval estimation based on the smoothed bootstrap and second-order bootstrap samples. The changes resulted from the integrated approach in the interval estimation of the seismic hazard functions with respect to the approach, which neglects the uncertainty of the mean activity rate estimates have been studied using Monte Carlo simulations and two real dataset examples. The results indicate that the uncertainty of mean activity rate affects significantly the interval estimates of hazard functions only when the product of activity rate and the time period, for which the hazard is estimated, is no more than 5.0. When this product becomes greater than 5.0, the impact of the uncertainty of cumulative distribution function of magnitude dominates the impact of the uncertainty of mean activity rate in the aggregated uncertainty of the hazard functions. Following, the interval estimates with and without inclusion of the uncertainty of mean activity rate converge. The presented algorithm is generic and can be applied also to capture the propagation of uncertainty of estimates, which are parameters of a multiparameter function, onto this function.
2014-01-01
Background Home hazards are associated with toddlers receiving unintentional home injuries (UHI). These result in not only physical and psychological difficulties for children, but also economic losses and additional stress for their families. Few researchers pay attention to predictors of home hazards among toddlers in a systematic way. The purpose of this study is firstly to describe the characteristics of homes with hazards and secondly to explore the predicted relationship of children, parents and family factors to home hazards among toddlers aged 24–47 months in Wenzhou, China. Methods A random cluster sampling was employed to select 366 parents having children aged 24 – 47 months from 13 kindergartens between March and April of 2012. Four instruments assessed home hazards, demographics, parent’s awareness of UHI, as well as family functioning. Results Descriptive statistics showed that the mean of home hazards was 12.29 (SD = 6.39). The nine kinds of home hazards that were identified in over 50% of households were: plastic bags (74.3%), coin buttons (69.1%), and toys with small components (66.7%) etc. Multivariate linear regression revealed that the predictors of home hazards were the child’s age, the child’s residential status and family functioning (b = .19, 2.02, - .07, p < .01, < .05 and < .01, respectively). Conclusions The results showed that a higher number of home hazards were significantly attributed to older toddlers, migrant toddlers and poorer family functioning. This result suggested that heath care providers should focus on the vulnerable family and help the parents assess home hazards. Further study is needed to find interventions on how to manage home hazards for toddlers in China. PMID:24953678
Lallukka, Tea; Ferrie, Jane E; Rahkonen, Ossi; Shipley, Martin J; Pietiläinen, Olli; Kivimäki, Mika; Marmot, Michael G; Lahelma, Eero
2013-09-01
The main aims of this longitudinal study were to (i) examine associations between changes in economic difficulties and health functioning among middle-aged employees and (ii) assess whether the associations remained after considering conventional domains of socioeconomic position. The associations were tested in two European welfare state occupational cohorts to strengthen the evidence base and improve generalizability. Data came from two cohorts: the Finnish Helsinki Health Study (baseline 2000-2002, follow-up 2007, N = 6328) and the British Whitehall II Study (baseline 1997-1999, follow-up 2003-2004, N = 4350). Responses to the survey item "finding it hard to afford adequate food and clothes and pay bills" repeated at baseline and follow-up were used to examine persistent, increasing, and decreasing economic difficulties. Poor physical and mental health functioning were denoted as being in the lowest quartile of the Short Form 36 physical and mental component summary. Logistic regression analyses were adjusted for sex, age, childhood economic difficulties, household income at baseline and follow-up, employment status at follow-up, and baseline health functioning. We observed strong sex- and age-adjusted associations between increasing [odds ratio (OR) range 1.69-2.96] and persistent (OR range 2.54-3.21) economic difficulties and poorer physical and mental health functioning in both British and Finnish occupational cohorts. These associations remained after full adjustments. Those reporting decreasing difficulties over follow-up also had poorer functioning (OR range 1.30-1.61) compared to those who did not have difficulties at baseline, possibly reflecting residual effects of economic difficulties at baseline. Changes in economic difficulties are associated with poorer physical and mental health functioning independent of income, employment status, and baseline health functioning.
Marte, Thomas; Saely, Christoph H; Schmid, Fabian; Koch, Lorena; Drexel, Heinz
2009-01-01
The impact of atrial fibrillation (AF) on future coronary events is uncertain. In particular, the prognostic impact of AF in the clinically important population of coronary patients who undergo angiography is unknown. The aim of this study was to investigate (1) the prevalence of AF, (2) its association with coronary atherosclerosis, and (3) its impact on future coronary events in patients who undergo angiography. Electrocardiograms were evaluated in a consecutive series of 613 patients who underwent coronary angiography. Prospectively, death and cardiovascular events were recorded over 4.0 +/- 0.6 years. Among these patients, 37 (6%) at baseline had AF, and 576 (94%) were in sinus rhythm. The presence of AF was associated with a lower prevalence of coronary artery disease and of coronary diameter narrowing >or=50% on baseline angiography. However, prospectively, patients with AF were at a strongly increased risk for all-cause mortality (adjusted hazard ratio 5.15, 95% confidence interval 2.36 to 11.26, p <0.001), coronary death (hazard ratio 8.16, 95% confidence interval 2.89 to 23.09, p <0.001), and major coronary events (hazard ratio 3.80, 95% confidence interval 1.45 to 9.94, p = 0.007). In conclusion, although inversely associated with the presence of angiographically determined coronary atherosclerosis, AF is a strong predictor of death and future coronary events in patients with coronary artery disease who undergo coronary angiography.
Enhancing fire department home visiting programs: results of a community intervention trial.
Gielen, Andrea C; Shields, Wendy; Frattaroli, Shannon; McDonald, Eileen; Jones, Vanya; Bishai, David; O'Brocki, Raymond; Perry, Elise C; Bates-Hopkins, Barbara; Tracey, Pat; Parsons, Stephanie
2013-01-01
This study evaluates the impact of an enhanced fire department home visiting program on community participation and installation of smoke alarms, and describes the rate of fire and burn hazards observed in homes. Communities were randomly assigned to receive either a standard or enhanced home visiting program. Before implementing the program, 603 household surveys were completed to determine comparability between the communities. During a 1-year intervention period, 171 home visits took place with 8080 homes. At baseline, 60% of homes did not have working smoke alarms on every level, 44% had unsafe water temperatures, and 72% did not have carbon monoxide alarms. Residents in the enhanced community relative to those in the standard community were significantly more likely to let the fire fighters into their homes (75 vs 62%). Among entered homes, those in the enhanced community were significantly more likely to agree to have smoke alarms installed (95 vs 92%), to be left with a working smoke alarm on every level of the home (84 vs 78%), and to have more smoke alarms installed per home visited (1.89 vs 1.74). The high baseline rates of home hazards suggest that fire department home visiting programs should take an "all hazards" approach. Community health workers and community partnerships can be effective in promoting fire departments' fire and life safety goals. Public health academic centers should partner with the fire service to help generate evidence on program effectiveness that can inform decision making about resource allocation for prevention.
Michaëlsson, Karl; Wolk, Alicja; Melhus, Håkan; Byberg, Liisa
2017-01-01
Abstract High milk consumption might shorten life span through increased oxidative stress. We aimed to determine whether higher mortality rates with high milk consumption are modified by fruit and vegetable intake or total antioxidant intake (oxygen radical absorbance capacity). We used information from food frequency questionnaires completed by 61,420 women in a Swedish cohort (22,391 deaths from the 1987–1990 baseline onward), 36,714 women from a second survey (1997) of this cohort, and 45,280 Swedish men (15,478 deaths from the 1998 baseline onward). Compared with low consumption of milk (<1 glass/day) and high consumption of fruits/vegetables (≥5 servings/day), time-updated information revealed an adjusted hazard ratio for death of 2.79 (95% confidence interval (CI): 2.42, 3.21) in women who consumed ≥3 glasses of milk/day and <1 serving/day of fruit/vegetables and a hazard ratio of 1.60 (95% CI: 1.40, 1.82) in women who consumed the same amount of milk but ≥5 servings/day of fruits/vegetables. The same comparisons in men, based on a single food frequency questionnaire, displayed hazard ratios of 1.31 (95% CI: 1.14, 1.51) and 1.07 (95% CI: 0.97, 1.18), respectively. Total antioxidant consumption showed similar patterns as fruit/vegetable intakes. Dietary antioxidant intake, especially in women, seems to modify the elevated death rate associated with high milk consumption. PMID:28184428
Backhans, Mona Christina; Balliu, Natalja; Lundin, Andreas; Hemmingsson, Tomas
2016-11-01
This study examined the associations between unemployment and alcohol-related hospitalization or mortality and to what extent these associations may be confounded by alcohol consumption and alcohol problems before unemployment. The study was based on the Stockholm Public Health Cohort (SPHC), a population-based stratified random sample with a baseline questionnaire in 2002/2003 and record linkages up to year 2011. The final sample in the study consists of 15,841 people aged 18-60 years. Unemployment was defined as any registration at the public employment services during 2003-2005. The outcome was alcohol-related hospitalization and alcohol-related mortality during 2006-2011. Confounders were age, sex, and education, and we further adjusted for baseline alcohol consumption and alcohol-related hospitalization before the study period. Cox proportional hazard models were fit, and associations were expressed as hazard ratios (HRs). In the fully adjusted model, unemployment was associated with an increased risk of alcohol-related hospitalization or mortality, with a more than threefold hazard (HR = 3.38, 95% CI [1.81, 6.31]) compared with no unemployment during the exposure period. There was a moderate attenuating effect of prior alcohol consumption and alcohol-related hospitalization. Any unemployment in 2003-2005 was highly related to having experienced an alcohol-related diagnosis during the 6-year follow-up, even after controlling for risky use of alcohol and prior hospitalization.
Abe, Takumi; Tsuji, Taishi; Kitano, Naruki; Muraki, Toshiaki; Hotta, Kazushi; Okura, Tomohiro
2015-01-01
The purpose of this study was to investigate whether the degree of improvement in cognitive function achieved with an exercise intervention in community-dwelling older Japanese women is affected by the participant's baseline cognitive function and age. Eighty-eight women (mean age: 70.5±4.2 years) participated in a prevention program for long-term care. They completed the Square-Stepping Exercise (SSE) program once a week, 120 minutes/session, for 11 weeks. We assessed participants' cognitive function using 5 cognitive tests (5-Cog) before and after the intervention. We defined cognitive function as the 5-Cog total score and defined the change in cognitive function as the 5-cog post-score minus the pre-score. We divided participants into four groups based on age (≤69 years or ≥70 years) and baseline cognitive function level (above vs. below the median cognitive function level). We conducted two-way analysis of variance. All 4 groups improved significantly in cognitive function after the intervention. There were no baseline cognitive function level×age interactions and no significant main effects of age, although significant main effects of baseline cognitive function level (P=0.004, η(2)=0.09) were observed. Square-Stepping Exercise is an effective exercise for improving cognitive function. These results suggest that older adults with cognitive decline are more likely to improve their cognitive function with exercise than if they start the intervention with high cognitive function. Furthermore, during an exercise intervention, baseline cognitive function level may have more of an effect than a participant's age on the degree of cognitive improvement.
Controlling hazardous energy sources (lockout/tagout)
NASA Technical Reports Server (NTRS)
Dominguez, Manuel B.
1991-01-01
The minimum requirements as established by the Occupational Safety and Health Administration (OSHA) standard 29 CFR 1910.147 are discussed for preventing the unexpected operation of equipment or release of energy which could cause injury to personnel, damage to equipment, harm to the environment, or loss or compromise of test data. Safety requirements both for government and contractor personnel are explained for potentially hazardous energy sources during work operations at LeRC (Cleveland and Plum Brook Stations). Basic rules are presented to ensure protection against harmful exposures, and baseline implementation requirements are discussed from which detailed lockout/tagout procedures can be developed for individual equipment items. Examples of energy sources covered by this document include electrical, pneumatic, mechanical, chemical, cryogenic, thermal, spring tension/compression suspended or moving loads, and other potentially hazardous sources. Activities covered by this standard include, but are not limited to, construction, maintenance, installation, calibration, inspection, cleaning, or repair.
Controlling hazardous energy sources (lockout/tagout)
NASA Astrophysics Data System (ADS)
Dominguez, Manuel B.
1991-10-01
The minimum requirements as established by the Occupational Safety and Health Administration (OSHA) standard 29 CFR 1910.147 are discussed for preventing the unexpected operation of equipment or release of energy which could cause injury to personnel, damage to equipment, harm to the environment, or loss or compromise of test data. Safety requirements both for government and contractor personnel are explained for potentially hazardous energy sources during work operations at LeRC (Cleveland and Plum Brook Stations). Basic rules are presented to ensure protection against harmful exposures, and baseline implementation requirements are discussed from which detailed lockout/tagout procedures can be developed for individual equipment items. Examples of energy sources covered by this document include electrical, pneumatic, mechanical, chemical, cryogenic, thermal, spring tension/compression suspended or moving loads, and other potentially hazardous sources. Activities covered by this standard include, but are not limited to, construction, maintenance, installation, calibration, inspection, cleaning, or repair.
Chapter 12 - Mapping wildland fuel across large regions for the LANDFIRE Prototype Project
Robert E. Keane; Tracey Frescino; Matthew C. Reeves; Jennifer L. Long
2006-01-01
The Landscape Fire and Resource Management Planning Tools Prototype Project, or LANDFIRE Prototype Project, required that the entire array of wildland fuel characteristics be mapped to provide fire and landscape managers with consistent baseline geo-spatial information to plan projects for hazardous fuel mitigation and to improve public and firefighter safety. Fuel...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-28
..., exposure and hazard, the requirements are designed to be flexible. Test notes to the data requirements... data and labeling requirements. In terms of costs, using pre-2003 costs as the baseline, the...-0060 (EPA ICR No. 0277). 3. The activities associated with the application for an experimental use...
Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong
2016-10-01
Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.
Oyarzabal, Omar A; Rowe, Ellen
2017-04-01
The terms hazard and risk are significant building blocks for the organization of risk-based food safety plans. Unfortunately, these terms are not clear for some personnel working in food manufacturing facilities. In addition, there are few examples of active learning modules for teaching adult participants the principles of hazard analysis and critical control points (HACCP). In this study, we evaluated the effectiveness of an active learning module to teach hazard and risk to participants of HACCP classes provided by the University of Vermont Extension in 2015 and 2016. This interactive module is comprised of a questionnaire; group playing of a dice game that we have previously introduced in the teaching of HACCP; the discussion of the terms hazard and risk; and a self-assessment questionnaire to evaluate the teaching of hazard and risk. From 71 adult participants that completed this module, 40 participants (56%) provided the most appropriate definition of hazard, 19 participants (27%) provided the most appropriate definition of risk, 14 participants (20%) provided the most appropriate definitions of both hazard and risk, and 23 participants (32%) did not provide an appropriate definition for hazard or risk. Self-assessment data showed an improvement in the understanding of these terms (P < 0.05). Thirty participants (42%) stated that the most valuable thing they learned with this interactive module was the difference between hazard and risk, and 40 participants (65%) responded that they did not attend similar presentations in the past. The fact that less than one third of the participants answered properly to the definitions of hazard and risk at baseline is not surprising. However, these results highlight the need for the incorporation of modules to discuss these important food safety terms and include more active learning modules to teach food safety classes. This study suggests that active learning helps food personnel better understand important food safety terms that serve as building blocks for the understanding of more complex food safety topics.
Rothschild, Anthony J.; Lapane, Kate L.
2016-01-01
Abstract Objective: To characterize the association between functional impairment and major depression subtypes at baseline and to characterize changes in subtypes by functional impairment level in women receiving citalopram in level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial. Method: Women who completed baseline and week 12 study visits were included. Items from the self-reported Quick Inventory of Depressive Symptomatology were used to define the latent depression subtypes. The Work and Social Adjustment Scale was used to classify baseline functional impairment. A latent transition analysis model provided estimates of the prevalence of subtype membership and transition probabilities by functional impairment level. Results: Of the 755 women included, 69% had major functional impairment at baseline. Regardless of functional impairment level, the subtypes were differentiated by depression severity, appetite changes, psychomotor disturbances, and insomnia. Sixty-seven percent of women with normal/significant functional impairment and 60% of women with major impairment were likely to transition to a symptom resolution subtype at week 12. Women with baseline major impairment who were in the severe with psychomotor agitation subtype at the beginning of the study were least likely to transition to the symptom resolution subtype (4% chance). Conclusions: Functional impairment level was related to both the baseline depression subtype and the likelihood of moving to a different subtype. These results underscore the need to incorporate not only depression symptoms but also functioning in the assessment and treatment of depression. PMID:26488110
Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar
2017-12-01
The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and < 0.0001, respectively). On ROC analysis, a threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor response (95% sensitivity, 93% specificity). Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.
Changes in physical activity and all-cause mortality in COPD.
Vaes, Anouk W; Garcia-Aymerich, Judith; Marott, Jacob L; Benet, Marta; Groenen, Miriam T J; Schnohr, Peter; Franssen, Frits M E; Vestbo, Jørgen; Wouters, Emiel F M; Lange, Peter; Spruit, Martijn A
2014-11-01
Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis. ©ERS 2014.
Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.
Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong
2017-04-01
This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, P<0.001). When HR of the 1st quartile was regarded as the reference, HRs for abdominal obesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend <0.001]. Although the risk of incident abdominal obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.
Virtanen, M; Ferrie, J E; Singh-Manoux, A; Shipley, M J; Stansfeld, S A; Marmot, M G; Ahola, K; Vahtera, J; Kivimäki, M
2011-12-01
Although long working hours are common in working populations, little is known about the effect of long working hours on mental health. We examined the association between long working hours and the onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 years (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997-1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002-2004). In a prospective analysis of participants with no depressive (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold [95% confidence interval (CI) 1.06-2.61] risk of depressive symptoms and a 1.74-fold (95% CI 1.15-2.61) risk of anxiety symptoms among employees working more than 55 h/week compared with employees working 35-40 h/week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women [hazard ratios (HRs) 2.67 (95% CI 1.07-6.68) and 2.84 (95% CI 1.27-6.34) respectively] but not men [1.30 (0.77-2.19) and 1.43 (0.89-2.30)]. Working long hours is a risk factor for the development of depressive and anxiety symptoms in women.
Saat, Mohd Rapik; Barkan, Christopher P L
2011-05-15
North America railways offer safe and generally the most economical means of long distance transport of hazardous materials. Nevertheless, in the event of a train accident releases of these materials can pose substantial risk to human health, property or the environment. The majority of railway shipments of hazardous materials are in tank cars. Improving the safety design of these cars to make them more robust in accidents generally increases their weight thereby reducing their capacity and consequent transportation efficiency. This paper presents a generalized tank car safety design optimization model that addresses this tradeoff. The optimization model enables evaluation of each element of tank car safety design, independently and in combination with one another. We present the optimization model by identifying a set of Pareto-optimal solutions for a baseline tank car design in a bicriteria decision problem. This model provides a quantitative framework for a rational decision-making process involving tank car safety design enhancements to reduce the risk of transporting hazardous materials. Copyright © 2011 Elsevier B.V. All rights reserved.
Expected hazards and hospital beds in host cities of the 2014 FIFA World Cup in Brazil.
Miranda, Elaine Silva; Shoaf, Kimberley; Silva, Raulino Sabino da; Freitas, Carolina Figueiredo; Osorio-de-Castro, Claudia Garcia Serpa
2017-06-12
Planning for mass gatherings involves health system preparedness based on an understanding of natural and technological hazards identified through prior risk assessment. We present the expected hazards reported by health administrators of the host cities for the 2014 FIFA World Cup in Brazil and discuss the hazards considering minimal available public hospital beds in the 12 cities at the time of the event. Four different groups of respondents were interviewed: pharmaceutical service administrators and overall health administrators at both the municipal and hospital levels. The hospital bed occupancy rate was calculated, based on the Brazilian Health Informatics Department (DATASUS). The number of surplus beds was calculated using parameters from the literature regarding surge and mass casualty needs and number of unoccupied beds. In all groups, physical injuries ranked first, followed by emerging and endemic diseases. Baseline occupancy rates were high (95%CI: 0.93-2.19) in all 12 cities. Total shortage, considering all the cities, ranged from -47,670 (for surges) to -60,569 beds (for mass casualties). The study can contribute to discussions on mass-gathering preparedness.
Konagaya, Yoko; Watanabe, Tomoyuki; Ohta, Toshiki
2012-01-01
The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.
Past Decline Versus Current eGFR and Subsequent ESRD Risk.
Kovesdy, Csaba P; Coresh, Josef; Ballew, Shoshana H; Woodward, Mark; Levin, Adeera; Naimark, David M J; Nally, Joseph; Rothenbacher, Dietrich; Stengel, Benedicte; Iseki, Kunitoshi; Matsushita, Kunihiro; Levey, Andrew S
2016-08-01
eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2). Copyright © 2016 by the American Society of Nephrology.
Casellas, J; Bach, R
2012-06-01
Lambing interval is a relevant reproductive indicator for sheep populations under continuous mating systems, although there is a shortage of selection programs accounting for this trait in the sheep industry. Both the historical assumption of small genetic background and its unorthodox distribution pattern have limited its implementation as a breeding objective. In this manuscript, statistical performances of 3 alternative parametrizations [i.e., symmetric Gaussian mixed linear (GML) model, skew-Gaussian mixed linear (SGML) model, and piecewise Weibull proportional hazard (PWPH) model] have been compared to elucidate the preferred methodology to handle lambing interval data. More specifically, flock-by-flock analyses were performed on 31,986 lambing interval records (257.3 ± 0.2 d) from 6 purebred Ripollesa flocks. Model performances were compared in terms of deviance information criterion (DIC) and Bayes factor (BF). For all flocks, PWPH models were clearly preferred; they generated a reduction of 1,900 or more DIC units and provided BF estimates larger than 100 (i.e., PWPH models against linear models). These differences were reduced when comparing PWPH models with different number of change points for the baseline hazard function. In 4 flocks, only 2 change points were required to minimize the DIC, whereas 4 and 6 change points were needed for the 2 remaining flocks. These differences demonstrated a remarkable degree of heterogeneity across sheep flocks that must be properly accounted for in genetic evaluation models to avoid statistical biases and suboptimal genetic trends. Within this context, all 6 Ripollesa flocks revealed substantial genetic background for lambing interval with heritabilities ranging between 0.13 and 0.19. This study provides the first evidence of the suitability of PWPH models for lambing interval analysis, clearly discarding previous parametrizations focused on mixed linear models.
Augmented Reality Cues and Elderly Driver Hazard Perception
Schall, Mark C.; Rusch, Michelle L.; Lee, John D.; Dawson, Jeffrey D.; Thomas, Geb; Aksan, Nazan; Rizzo, Matthew
2013-01-01
Objective Evaluate the effectiveness of augmented reality (AR) cues in improving driving safety in elderly drivers who are at increased crash risk due to cognitive impairments. Background Cognitively challenging driving environments pose a particular crash risk for elderly drivers. AR cueing is a promising technology to mitigate risk by directing driver attention to roadway hazards. This study investigates whether AR cues improve or interfere with hazard perception in elderly drivers with age-related cognitive decline. Methods Twenty elderly (Mean= 73 years, SD= 5 years), licensed drivers with a range of cognitive abilities measured by a speed of processing (SOP) composite participated in a one-hour drive in an interactive, fixed-base driving simulator. Each participant drove through six, straight, six-mile-long rural roadway scenarios following a lead vehicle. AR cues directed attention to potential roadside hazards in three of the scenarios, and the other three were uncued (baseline) drives. Effects of AR cueing were evaluated with respect to: 1) detection of hazardous target objects, 2) interference with detecting nonhazardous secondary objects, and 3) impairment in maintaining safe distance behind a lead vehicle. Results AR cueing improved the detection of hazardous target objects of low visibility. AR cues did not interfere with detection of nonhazardous secondary objects and did not impair ability to maintain safe distance behind a lead vehicle. SOP capacity did not moderate those effects. Conclusion AR cues show promise for improving elderly driver safety by increasing hazard detection likelihood without interfering with other driving tasks such as maintaining safe headway. PMID:23829037
Hazard function theory for nonstationary natural hazards
Read, Laura K.; Vogel, Richard M.
2016-04-11
Impact from natural hazards is a shared global problem that causes tremendous loss of life and property, economic cost, and damage to the environment. Increasingly, many natural processes show evidence of nonstationary behavior including wind speeds, landslides, wildfires, precipitation, streamflow, sea levels, and earthquakes. Traditional probabilistic analysis of natural hazards based on peaks over threshold (POT) generally assumes stationarity in the magnitudes and arrivals of events, i.e., that the probability of exceedance of some critical event is constant through time. Given increasing evidence of trends in natural hazards, new methods are needed to characterize their probabilistic behavior. The well-developed field ofmore » hazard function analysis (HFA) is ideally suited to this problem because its primary goal is to describe changes in the exceedance probability of an event over time. HFA is widely used in medicine, manufacturing, actuarial statistics, reliability engineering, economics, and elsewhere. HFA provides a rich theory to relate the natural hazard event series ( X) with its failure time series ( T), enabling computation of corresponding average return periods, risk, and reliabilities associated with nonstationary event series. This work investigates the suitability of HFA to characterize nonstationary natural hazards whose POT magnitudes are assumed to follow the widely applied generalized Pareto model. We derive the hazard function for this case and demonstrate how metrics such as reliability and average return period are impacted by nonstationarity and discuss the implications for planning and design. As a result, our theoretical analysis linking hazard random variable X with corresponding failure time series T should have application to a wide class of natural hazards with opportunities for future extensions.« less
Hazard function theory for nonstationary natural hazards
DOE Office of Scientific and Technical Information (OSTI.GOV)
Read, Laura K.; Vogel, Richard M.
Impact from natural hazards is a shared global problem that causes tremendous loss of life and property, economic cost, and damage to the environment. Increasingly, many natural processes show evidence of nonstationary behavior including wind speeds, landslides, wildfires, precipitation, streamflow, sea levels, and earthquakes. Traditional probabilistic analysis of natural hazards based on peaks over threshold (POT) generally assumes stationarity in the magnitudes and arrivals of events, i.e., that the probability of exceedance of some critical event is constant through time. Given increasing evidence of trends in natural hazards, new methods are needed to characterize their probabilistic behavior. The well-developed field ofmore » hazard function analysis (HFA) is ideally suited to this problem because its primary goal is to describe changes in the exceedance probability of an event over time. HFA is widely used in medicine, manufacturing, actuarial statistics, reliability engineering, economics, and elsewhere. HFA provides a rich theory to relate the natural hazard event series ( X) with its failure time series ( T), enabling computation of corresponding average return periods, risk, and reliabilities associated with nonstationary event series. This work investigates the suitability of HFA to characterize nonstationary natural hazards whose POT magnitudes are assumed to follow the widely applied generalized Pareto model. We derive the hazard function for this case and demonstrate how metrics such as reliability and average return period are impacted by nonstationarity and discuss the implications for planning and design. As a result, our theoretical analysis linking hazard random variable X with corresponding failure time series T should have application to a wide class of natural hazards with opportunities for future extensions.« less
McCartney, Danielle; Desbrow, Ben; Irwin, Christopher
2017-01-02
Fatal vision goggles (FVGs) are image-distorting equipment used within driver education programs to simulate alcohol-related impairment. However, there is no empirical evidence comparing the behavioral effects associated with wearing FVGs to alcohol intoxication. The purpose of this study was to determine the validity of FVGs in producing alcohol-related impairment in simulated driving. Twenty-two healthy males (age: 23 ± 3 years, mean ± SD) participated in a placebo-controlled crossover design study involving 4 experimental trials. In each trial, participants completed a baseline level simulated driving task followed by an experimental driving task, involving one of 4 treatments: (1) a dose of alcohol designed to elicit 0.080% breath alcohol concentration (BrAC; AB), (2) an alcohol placebo beverage (PB), (3) FVG (estimated % blood alcohol concentration [BAC] 0.070-0.100+), and (4) placebo goggles (PGs). The driving tasks included 3 separate scenarios lasting ∼5 min each; these were a simple driving scenario, a complex driving scenario, and a hazard perception driving scenario. Selected lateral control parameters (standard deviation of lane position [SDLP]; total number of lane crossings [LCs]) and longitudinal control parameters (average speed; standard deviation of speed [SDSP]; distance headway; minimum distance headway) were monitored during the simple and complex driving scenarios. Latency to 2 different stimuli (choice reaction time [CRT]) was tested in the hazard perception driving scenario. Subjective ratings of mood and attitudes toward driving were also provided during each of the trials. Neither placebo treatment influenced simulated driving performance. Mean BrAC was 0.060 ± 0.010% at the time of driving on the AB trial. Lateral control: In the simple driving scenario, SDLP and LC were not affected under any of the experimental treatments. However, in the complex driving scenario, significantly greater SDLP was observed on both the FVG and AB trials compared to their respective baseline drives. LC increased significantly from baseline on the AB trial only. Longitudinal control: Speed was not affected by any of the experimental treatments; however, SDSP increased significantly from baseline on the FVG trial. A significant reduction in distance headway and minimum distance headway was detected on the FVG trial compared to baseline. Hazard perception: Neither AB nor FVG trials were influential on CRT. Subjective mood ratings were significantly altered on the AB and FVG trials compared to baseline and placebo conditions. Participants reported reduced willingness and ability to drive under the active treatments (AB and FVG) than the placebo treatments (PB and PG). FVGs may have some utility in replicating alcohol-related impairment on specific driving performance measurements. Hence, the equipment may offer an alternative approach to researching the impact of alcohol intoxication on simulated driving performance among populations where the provision of alcohol would otherwise be unethical (e.g., prelicensed drivers).
PERSONNEL PROTECTION THROUGH RECONNAISSANCE ROBOTICS AT SUPERFUND REMEDIAL SITES
Investigation, mitigation, and clean-up of hazardous materials at Superfund sites normally require on-site workers to perform hazardous and sometimes potentially dangerous functions. uch functions include site surveys and the reconnaissance for airborne and buried toxic environme...
DEMONSTRATION OF AUTONOMOUS AIR MONITORING THROUGH ROBOTICS
Hazardous and/or tedious functions are often performed by on-site workers during investigation, mitigation and clean-up of hazardous substances. These functions include site surveys, sampling and analysis, excavation, and treatment and preparation of wastes for shipment to chemic...
Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.
Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan
2017-10-01
Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.
Lord, Kevin; Moll, David; Lindsey, John K.; Mahne, Sarah; Raman, Girija; Dugas, Tammy; Cormier, Stephania; Troxlair, Dana; Lomnicki, Slawo; Dellinger, Barry; Varner, Kurt
2011-01-01
Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown Norway rats were dosed (8 mg/kg, i.t.) 24 hr prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed. PMID:21385100
Mankikar, Deepa; Campbell, Carla; Greenberg, Rachael
2016-09-09
This evaluation examined whether participation in a home-based environmental educational intervention would reduce exposure to health and safety hazards and asthma-related medical visits. The home intervention program focused on vulnerable, low-income households, where children had asthma, were at risk for lead poisoning, or faced multiple unsafe housing conditions. Home visitors conducted two home visits, two months apart, consisting of an environmental home assessment, Healthy Homes education, and distribution of Healthy Homes supplies. Measured outcomes included changes in participant knowledge and awareness of environmental home-based hazards, rate of children's asthma-related medical use, and the presence of asthma triggers and safety hazards. Analysis of 2013-2014 baseline and post-intervention program data for a cohort of 150 families revealed a significantly lower three-month rate (p < 0.05) of children's asthma-related doctor visits and hospital admissions at program completion. In addition, there were significantly reduced reports of the presence of home-based hazards, including basement or roof leaks (p = 0.011), plumbing leaks (p = 0.019), and use of an oven to heat the home (p < 0.001). Participants' pre- and post- test scores showed significant improvement (p < 0.05) in knowledge and awareness of home hazards. Comprehensive home interventions may effectively reduce environmental home hazards and improve the health of asthmatic children in the short term.
Clinical Relevance of Baseline TCP in Transcatheter Aortic Valve Replacement.
Sannino, Anna; Stoler, Robert C; Hebeler, Robert F; Szerlip, Molly; Mack, Michael J; Grayburn, Paul A
2017-10-01
To investigate the influence of baseline thrombocytopenia (TCP) on short-term and long-term outcomes after transcatheter aortic valve replacement (TAVR). A total of 732 consecutive patients with severe, symptomatic aortic stenosis undergoing TAVR from January 2012 to December 2015 were included. Primary outcomes of interest were the relationship of baseline TCP with 30-day and 1-year all-cause mortality. Secondary outcomes of interest were procedural complications and in-hospital mortality in the same subgroups. The prevalence of TCP (defined as platelet count <150 × 109/L) at baseline was 21.9%, of whom 4.0% had moderate/severe TCP (defined as platelet count <100 × 109/L). Compared to no or mild TCP, moderate/severe TCP at baseline was associated with a significantly higher 30-day mortality (23.3% vs 2.3% and 3.1%, respectively; P<.001) and 1-year mortality (40.0% vs 8.3% and 13.4%, respectively; P<.001). In Cox regression analysis, moderate/severe baseline TCP was an independent predictor of 30-day and 1-year mortality (hazard ratio [HR], 13.18; 95% confidence interval [CI], 4.49-38.64; P<.001 and HR, 5.90; 95% CI, 2.68-13.02; P<.001, respectively). In conclusion, baseline TCP is a strong predictor of mortality in TAVR patients, possibly identifying a specific subgroup of frail patients; therefore, it should be taken into account when addressing TAVR risk.
NASA Astrophysics Data System (ADS)
Bezawada, Rajesh; Uijt de Haag, Maarten
2010-04-01
This paper discusses the results of an initial evaluation study of hazard and integrity monitor functions for use with integrated alerting and notification. The Hazard and Integrity Monitor (HIM) (i) allocates information sources within the Integrated Intelligent Flight Deck (IIFD) to required functionality (like conflict detection and avoidance) and determines required performance of these information sources as part of that function; (ii) monitors or evaluates the required performance of the individual information sources and performs consistency checks among various information sources; (iii) integrates the information to establish tracks of potential hazards that can be used for the conflict probes or conflict prediction for various time horizons including the 10, 5, 3, and <3 minutes used in our scenario; (iv) detects and assesses the class of the hazard and provide possible resolutions. The HIM monitors the operation-dependent performance parameters related to the potential hazards in a manner similar to the Required Navigation Performance (RNP). Various HIM concepts have been implemented and evaluated using a previously developed sensor simulator/synthesizer. Within the simulation framework, various inputs to the IIFD and its subsystems are simulated, synthesized from actual collected data, or played back from actual flight test sensor data. The framework and HIM functions are implemented in SimulinkR, a modeling language developed by The MathworksTM. This modeling language allows for test and evaluation of various sensor and communication link configurations as well as the inclusion of feedback from the pilot on the performance of the aircraft.
Perceived neighborhood safety and incident mobility disability among elders: the hazards of poverty.
Clark, Cheryl R; Kawachi, Ichiro; Ryan, Louise; Ertel, Karen; Fay, Martha E; Berkman, Lisa F
2009-05-28
We investigated whether lack of perceived neighborhood safety due to crime, or living in high crime neighborhoods was associated with incident mobility disability in elderly populations. We hypothesized that low-income elders and elders at retirement age (65 - 74) would be at greatest risk of mobility disability onset in the face of perceived or measured crime-related safety hazards. We conducted the study in the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE), a longitudinal cohort study of community-dwelling elders aged 65 and older who were residents of New Haven, Connecticut in 1982. Elders were interviewed beginning in 1982 to assess mobility (ability to climb stairs and walk a half mile), perceptions of their neighborhood safety due to crime, annual household income, lifestyle characteristics (smoking, alcohol use, physical activity), and the presence of chronic co-morbid conditions. Additionally, we collected baseline data on neighborhood crime events from the New Haven Register newspaper in 1982 to measure local area crime rates at the census tract level. At baseline in 1982, 1,884 elders were without mobility disability. After 8 years of follow-up, perceiving safety hazards was associated with increased risk of mobility disability among elders at retirement age whose incomes were below the federal poverty line (HR 1.56, 95% CI 1.02 - 2.37). No effect of perceived safety hazards was found among elders at retirement age whose incomes were above the poverty line. No effect of living in neighborhoods with high crime rates (measured by newspaper reports) was found in any sub-group. Perceiving a safety hazard due to neighborhood crime was associated with increased risk of incident mobility disability among impoverished elders near retirement age. Consistent with prior literature, retirement age appears to be a vulnerable period with respect to the effect of neighborhood conditions on elder health. Community violence prevention activities should address perceived safety among vulnerable populations, such as low-income elders at retirement age, to reduce future risks of mobility disability.
Perceived neighborhood safety and incident mobility disability among elders: the hazards of poverty
Clark, Cheryl R; Kawachi, Ichiro; Ryan, Louise; Ertel, Karen; Fay, Martha E; Berkman, Lisa F
2009-01-01
Background We investigated whether lack of perceived neighborhood safety due to crime, or living in high crime neighborhoods was associated with incident mobility disability in elderly populations. We hypothesized that low-income elders and elders at retirement age (65 – 74) would be at greatest risk of mobility disability onset in the face of perceived or measured crime-related safety hazards. Methods We conducted the study in the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE), a longitudinal cohort study of community-dwelling elders aged 65 and older who were residents of New Haven, Connecticut in 1982. Elders were interviewed beginning in 1982 to assess mobility (ability to climb stairs and walk a half mile), perceptions of their neighborhood safety due to crime, annual household income, lifestyle characteristics (smoking, alcohol use, physical activity), and the presence of chronic co-morbid conditions. Additionally, we collected baseline data on neighborhood crime events from the New Haven Register newspaper in 1982 to measure local area crime rates at the census tract level. Results At baseline in 1982, 1,884 elders were without mobility disability. After 8 years of follow-up, perceiving safety hazards was associated with increased risk of mobility disability among elders at retirement age whose incomes were below the federal poverty line (HR 1.56, 95% CI 1.02 – 2.37). No effect of perceived safety hazards was found among elders at retirement age whose incomes were above the poverty line. No effect of living in neighborhoods with high crime rates (measured by newspaper reports) was found in any sub-group. Conclusion Perceiving a safety hazard due to neighborhood crime was associated with increased risk of incident mobility disability among impoverished elders near retirement age. Consistent with prior literature, retirement age appears to be a vulnerable period with respect to the effect of neighborhood conditions on elder health. Community violence prevention activities should address perceived safety among vulnerable populations, such as low-income elders at retirement age, to reduce future risks of mobility disability. PMID:19476610
Bruckner, Tim A; Yoon, Jangho; Gonzales, Marco
2017-03-01
Increasing attention focuses on cardiovascular disease (CVD) among persons with SMI. We examined, among persons with SMI, whether co-occurring substance use disorder (SUD) elevates the risk of CVD death. We linked 2002-2007 Medicaid claims data on 121,817 persons with SMI to cause and date of death information. We applied a proportional hazards model that controls for co-morbidity at baseline, atypical antipsychotic prescription medications, age, gender and race/ethnicity. Results among persons with co-occurring SUD indicate a 24 % increased risk of CVD death (hazard ratio 1.24; 95 % confidence interval 1.17-1.33). We encourage further coordination of services for this population.
Hazards Data Distribution System (HDDS)
Jones, Brenda; Lamb, Rynn M.
2015-07-09
When emergencies occur, first responders and disaster response teams often need rapid access to aerial photography and satellite imagery that is acquired before and after the event. The U.S. Geological Survey (USGS) Hazards Data Distribution System (HDDS) provides quick and easy access to pre- and post-event imagery and geospatial datasets that support emergency response and recovery operations. The HDDS provides a single, consolidated point-of-entry and distribution system for USGS-hosted remotely sensed imagery and other geospatial datasets related to an event response. The data delivery services are provided through an interactive map-based interface that allows emergency response personnel to rapidly select and download pre-event ("baseline") and post-event emergency response imagery.
[The prognostic value of baseline serum free light chain in cardiac amyloidosis].
Zhao, Lei; Tian, Zhuang; Fang, Quan
2016-03-01
To analyze the prognostic value of baseline serum free light chain (sFLC) in light-chain (AL) cardiac amyloidosis. Twenty-seven patients with AL cardiac amyloidosis were retrospectively reviewed from January 2014 to January 2015. sFLC was measured by immuoturbidimetric assay. Baseline characteristics, echocardiographic parameters and electrocardiogram data were analyzed. According to the median baseline dFLC (involved sFLC minus uninvolved sFLC), patients were categorized into either the low dFLC(≤ 307 mg/L) or the high dFLC group (>307 mg/L). More subjects in the high dFLC group with early/late diastolic mitral velocity ratio (E/A ratio) over 2 (71.4% vs 30.8%, P=0.035), and subjects in this group had a shorter median survival time than those in the low dFLC group (3 months vs 17 months, P=0.004). A similar phenomenon for median survival time was observed when the subjects were redivided either by a new cut-off value of 180 mg/L for dFLC (low dFLC group: 17 months; high dFLC group: 4 months, P=0.014) or a κ/λ ratio, in which subjects with κ type sFLC-ratio ≤ 19.6 and λ type sFLC-ratio>0.065 were in the low sFLC-ratio group (17 months) and those with κ type sFLC-ratio > 19.6 and λ type sFLC-ratio ≤ 0.065 were in the high sFLC-ratio group (4 months, P=0.023). In multivariate analysis, dFLC and New York Heart Association (NYHA)classification of cardiac function were two risk factors associated with all-cause mortality in patients, among which the hazard ratio for higher dFLC was 4.28 (95%CI 1.55-11.8, P=0.005). The level of sFLC could be a marker for the prognosis of AL cardiac amyloidosis.
Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Jansa, Pavel; Kim, Nick H; Mayer, Eckhard; Pulido, Tomas; Wang, Chen; Colorado, Pablo; Fritsch, Arno; Meier, Christian; Nikkho, Sylvia; Hoeper, Marius M
2016-05-01
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers. Bayer Pharma AG. Copyright © 2016 Elsevier Ltd. All rights reserved.
Trail Making Test predicts physical impairment and mortality in older persons.
Vazzana, Rosamaria; Bandinelli, Stefania; Lauretani, Fabrizio; Volpato, Stefano; Lauretani, Fulvio; Di Iorio, Angelo; Abate, Michele; Corsi, Anna Maria; Milaneschi, Yuri; Guralnik, Jack M; Ferrucci, Luigi
2010-04-01
To examine whether performance in the Trail Making Test (TMT) predicts mobility impairment and mortality in older persons. Prospective cohort study. Community-dwelling older persons enrolled in the Invecchiare in Chianti (InCHIANTI) Study. Five hundred eighty-three participants aged 65 and older and free of major cognitive impairment (Mini-Mental State Examination score >21) with baseline data on TMT performance. Of these, 427 performed the Short Physical Performance Battery (SPPB) for the assessment of lower extremity function at baseline and after 6 years. Of the initial 583 participants, 106 died during a 9-year follow-up. The TMT Parts A and B (TMT-A and TMT-B) and SPPB were administered at baseline and 6-year follow-up. Impaired mobility was defined as an SPPB score less than 10. Vital status was ascertained over a 9-year follow-up. InCHIANTI participants in the fourth quartile of the time to complete TMT-B minus time to complete TMT-A (TMT (B-A)) were significantly more likely to develop an SPPB score less than 10 during the 6-year follow-up than those in the first quartile (relative risk (RR)=2.4, 95% confidence interval (CI)=1.4-3.9, P=.001). After adjusting for potential confounders, these findings were substantially unchanged (RR=2.2, 95% CI=1.4-3.6, P=.001). Worse performance on the TMT was associated with significantly greater decline in SPPB score over the 6-year follow-up, after adjusting for age, sex, and baseline SPPB scores (beta=-0.01, standard error=0.003, P=.004). During the 9-year follow-up, 18.2% of the participants died. After adjustment for age and sex, the proportion of participants who died was higher in participants in the worst than the best performance quartile of TMT (B-A) scores (hazard ratio (HR)=1.7, 95% CI=1.0-2.9, P=.048). Results were similar in a parsimonious adjusted model (HR=1.8, 95% CI=1.0-3.2, P=.04). Performance on the TMT is a strong, independent predictor of mobility impairment, accelerated decline in lower extremity function, and death in older adults living in the community. The TMT could be a useful addition to geriatric assessment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.
2014-02-01
Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less
Serum magnesium is associated with the risk of dementia.
Kieboom, Brenda C T; Licher, Silvan; Wolters, Frank J; Ikram, M Kamran; Hoorn, Ewout J; Zietse, Robert; Stricker, Bruno H; Ikram, M Arfan
2017-10-17
To determine if serum magnesium levels are associated with the risk of all-cause dementia and Alzheimer disease. Within the prospective population-based Rotterdam Study, we measured serum magnesium levels in 9,569 participants, free from dementia at baseline (1997-2008). Participants were subsequently followed up for incident dementia, determined according to the DSM-III-R criteria, until January 1, 2015. We used Cox proportional hazard regression models to associate quintiles of serum magnesium with incident all-cause dementia. We used the third quintile as a reference group and adjusted for age, sex, Rotterdam Study cohort, educational level, cardiovascular risk factors, kidney function, comorbidities, other electrolytes, and diuretic use. Our study population had a mean age of 64.9 years and 56.6% were women. During a median follow-up of 7.8 years, 823 participants were diagnosed with all-cause dementia. Both low serum magnesium levels (≤0.79 mmol/L) and high serum magnesium levels (≥0.90 mmol/L) were associated with an increased risk of dementia (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.02-1.69, and HR 1.30, 95% CI 1.02-1.67, respectively). Both low and high serum magnesium levels are associated with an increased risk of all-cause dementia. Our results warrant replication in other population-based studies. © 2017 American Academy of Neurology.
Smoothing spline ANOVA frailty model for recurrent event data.
Du, Pang; Jiang, Yihua; Wang, Yuedong
2011-12-01
Gap time hazard estimation is of particular interest in recurrent event data. This article proposes a fully nonparametric approach for estimating the gap time hazard. Smoothing spline analysis of variance (ANOVA) decompositions are used to model the log gap time hazard as a joint function of gap time and covariates, and general frailty is introduced to account for between-subject heterogeneity and within-subject correlation. We estimate the nonparametric gap time hazard function and parameters in the frailty distribution using a combination of the Newton-Raphson procedure, the stochastic approximation algorithm (SAA), and the Markov chain Monte Carlo (MCMC) method. The convergence of the algorithm is guaranteed by decreasing the step size of parameter update and/or increasing the MCMC sample size along iterations. Model selection procedure is also developed to identify negligible components in a functional ANOVA decomposition of the log gap time hazard. We evaluate the proposed methods with simulation studies and illustrate its use through the analysis of bladder tumor data. © 2011, The International Biometric Society.
Executive function processes predict mobility outcomes in older adults.
Gothe, Neha P; Fanning, Jason; Awick, Elizabeth; Chung, David; Wójcicki, Thomas R; Olson, Erin A; Mullen, Sean P; Voss, Michelle; Erickson, Kirk I; Kramer, Arthur F; McAuley, Edward
2014-02-01
To examine the relationship between performance on executive function measures and subsequent mobility outcomes in community-dwelling older adults. Randomized controlled clinical trial. Champaign-Urbana, Illinois. Community-dwelling older adults (N = 179; mean age 66.4). A 12-month exercise trial with two arms: an aerobic exercise group and a stretching and strengthening group. Established cognitive tests of executive function (flanker task, task switching, and a dual-task paradigm) and the Wisconsin card sort test. Mobility was assessed using the timed 8-foot up and go test and times to climb up and down a flight of stairs. Participants completed the cognitive tests at baseline and the mobility measures at baseline and after 12 months of the intervention. Multiple regression analyses were conducted to determine whether baseline executive function predicted postintervention functional performance after controlling for age, sex, education, cardiorespiratory fitness, and baseline mobility levels. Selective baseline executive function measurements, particularly performance on the flanker task (β = 0.15-0.17) and the Wisconsin card sort test (β = 0.11-0.16) consistently predicted mobility outcomes at 12 months. The estimates were in the expected direction, such that better baseline performance on the executive function measures predicted better performance on the timed mobility tests independent of intervention. Executive functions of inhibitory control, mental set shifting, and attentional flexibility were predictive of functional mobility. Given the literature associating mobility limitations with disability, morbidity, and mortality, these results are important for understanding the antecedents to poor mobility function that well-designed interventions to improve cognitive performance can attenuate. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
Morgan, Karen L. M.
2017-04-03
The U.S. Geological Survey (USGS), as part of the National Assessment of Storm-Induced Coastal Change Hazards project, conducts baseline and storm-response photography missions to document and understand the changes in vulnerability of the Nation's coasts to extreme storms. On June 9, 2011, the USGS conducted an oblique aerial photographic survey from Dauphin Island, Alabama, to Breton Island, Louisiana, aboard a Beechcraft BE90 King Air (aircraft) at an altitude of 500 feet (ft) (152 meters (m)) and approximately 1,200 ft (366 m) offshore. This mission was conducted to collect baseline data for assessing incremental changes in the beach and nearshore area and can be used to assess future coastal change.The photographs in this report are Joint Photographic Experts Group (JPEG) images. These photographs document the state of the barrier islands and other coastal features at the time of the survey.
Drazner, Mark H; Velez-Martinez, Mariella; Ayers, Colby R; Reimold, Sharon C; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Patel, Chetan B
2013-03-01
Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAP/PCWP ratio, and whether it conveys prognostic value, is not known. We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial database. Baseline characteristics, including echocardiographic assessment of right ventricular (RV) structure and function, and invasively measured hemodynamic parameters, were compared among tertiles of the RAP/PCWP ratio. Multivariable Cox proportional hazard models assessed the association of RAP/PCWP ratio with the primary ESCAPE outcome (6-month death or hospitalization [days]) adjusting for systolic blood pressure, blood urea nitrogen, 6-minute walk distance, and PCWP. The RAP/PCWP tertiles were 0.27 to 0.4 (tertile 1); 0.41 to 0.615 (tertile 2), and 0.62 to 1.21 (tertile 3). Increasing RAP/PCWP was associated with increasing median right atrial area (23, 26, 29 cm2, respectively; P<0.005), RV area in diastole (21, 27, 27 cm2, respectively; P<0.005), and pulmonary vascular resistance (2.4, 2.9, 3.6 woods units, respectively; P=0.003), and lower RV stroke work index (8.6, 8.4, 5.5 g·m/m2 per beat, respectively; P<0.001). RAP/PCWP ratio was associated with death or hospitalization within 6 months (hazard ratio, 1.16 [1, 1.4]; P<0.05). Increased RAP/PCWP ratio was associated with higher pulmonary vascular resistance, reduced RV function (manifest as a larger right atrium and ventricle and lower RV stroke work index), and an increased risk of adverse outcomes in patients with advanced heart failure.
Olfaction and risk of dementia in a biracial cohort of older adults.
Yaffe, Kristine; Freimer, Daniel; Chen, Honglei; Asao, Keiko; Rosso, Andrea; Rubin, Susan; Tranah, Greg; Cummings, Steve; Simonsick, Eleanor
2017-01-31
Prior studies indicate that olfactory function may be an early marker for cognitive impairment, but the body of evidence has been largely restricted to white populations. We studied 2,428 community-dwelling black and white older adults (baseline age 70-79 years) without dementia enrolled in the Health, Aging, and Body Composition (Health ABC) study. Olfaction was measured as odor identification (OI) with the 12-item Cross Cultural Smell Identification Test in year 3. We defined incident dementia over 12 years on the basis of hospitalization records, prescription for dementia medication, or 1.5-SD decline in race-stratified global cognition score. We assessed dementia risk associated with OI score (by tertile) using Cox proportional hazards models. All analyses were stratified by race. Poorer OI in older adults without dementia was associated with increased risk of dementia. After adjustment for demographics, medical comorbidities, and lifestyle characteristics, white participants in the poor or moderate OI tertile had greater risk of dementia (adjusted hazard ratio [HR] 3.34, 95% confidence interval [CI] 2.45-4.54; and HR 1.84, 95% CI 1.33-2.54, respectively) compared to those in the good tertile of function. Among blacks, worse OI was associated with an increased risk of dementia, but the magnitude of the effect was weaker (p for interaction = 0.04) for the poor OI tertile (adjusted HR 2.03, 95% CI 1.44-2.84) and for the moderate tertile (adjusted HR 1.42, 95% CI 0.97-2.10). There was no interaction between OI and APOE ε4 and risk of dementia. While the magnitude of the association was stronger in whites, we found that poor OI was associated with increased risk of dementia among both black and white older adults. © 2016 American Academy of Neurology.
Tomioka, Kimiko; Kurumatani, Norio; Hosoi, Hiroshi
2016-01-01
Background This study’s aim was to clarify the relationship of having hobbies and a purpose in life (PIL; in Japanese, ikigai) with mortality and a decline in the activities of daily living (ADL) and instrumental ADL (IADL) among the community-dwelling elderly. Methods Prospective observational data from residents aged ≥65 years who were at increased risk for death (n = 1853) and developing a decline in ADL (n = 1254) and IADL (n = 1162) were analyzed. Cox proportional hazard models were used for mortality analysis of data from February 2011 to November 2014. ADL and IADL were evaluated using the Barthel Index and the Tokyo Metropolitan Institute of Gerontology Index of Competence, respectively. ADL and IADL were assessed at baseline and follow-up and were evaluated using logistic regression models. Fully adjusted models included terms for age, gender, BMI, income, alcohol intake, smoking history, number of chronic diseases, cognitive function, and depression. Results During the follow-up of eligible participants, 248 had died, 119 saw a decline in ADL, and 178 saw a decline in IADL. In fully adjusted models, having neither hobbies nor PIL was significantly associated with an increased risk of mortality (hazard ratio 2.08; 95% confidence interval [CI], 1.47–2.94), decline in ADL (odds ratio 2.74; 95% CI, 1.44–5.21), and decline in IADL (odds ratio 1.89; 95% CI, 1.01–3.55) compared to having both hobbies and PIL. Conclusions Although effect modifications by cognitive functioning and depression cannot be ruled out, our findings suggest that having hobbies and PIL may extend not only longevity, but also healthy life expectancy among community-dwelling older adults. PMID:26947954
Tomioka, Kimiko; Kurumatani, Norio; Hosoi, Hiroshi
2016-07-05
This study's aim was to clarify the relationship of having hobbies and a purpose in life (PIL; in Japanese, ikigai) with mortality and a decline in the activities of daily living (ADL) and instrumental ADL (IADL) among the community-dwelling elderly. Prospective observational data from residents aged ≥65 years who were at increased risk for death (n = 1853) and developing a decline in ADL (n = 1254) and IADL (n = 1162) were analyzed. Cox proportional hazard models were used for mortality analysis of data from February 2011 to November 2014. ADL and IADL were evaluated using the Barthel Index and the Tokyo Metropolitan Institute of Gerontology Index of Competence, respectively. ADL and IADL were assessed at baseline and follow-up and were evaluated using logistic regression models. Fully adjusted models included terms for age, gender, BMI, income, alcohol intake, smoking history, number of chronic diseases, cognitive function, and depression. During the follow-up of eligible participants, 248 had died, 119 saw a decline in ADL, and 178 saw a decline in IADL. In fully adjusted models, having neither hobbies nor PIL was significantly associated with an increased risk of mortality (hazard ratio 2.08; 95% confidence interval [CI], 1.47-2.94), decline in ADL (odds ratio 2.74; 95% CI, 1.44-5.21), and decline in IADL (odds ratio 1.89; 95% CI, 1.01-3.55) compared to having both hobbies and PIL. Although effect modifications by cognitive functioning and depression cannot be ruled out, our findings suggest that having hobbies and PIL may extend not only longevity, but also healthy life expectancy among community-dwelling older adults.
Chan, Y-H; Lau, K-K; Yiu, K-H; Siu, C-W; Chan, H-T; Li, S-W; Tam, S; Lam, T-H; Lau, C-P; Tse, H-F
2012-04-01
Whether isoflavone has any effect on recurrent cardiovascular events is unknown. To investigate the relations between isoflavone intake and the risk of stroke recurrence. We recruited 127 consecutive patients with prior history of atherothrombotic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. Median isoflavone intake was 6.9 (range: 2.1 - 14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4 - 27.6] mth versus 5.0 [range: 4.1 - 5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4 - 27.6] mth versus 4.0 [range: 2.4 - 5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03 - 0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03 - 0.84], risk reduction 84%, p=0.030). Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE independent of baseline vascular function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.
Hazardous Drinking and Military Community Functioning: Identifying Mediating Risk Factors
ERIC Educational Resources Information Center
Foran, Heather M.; Heyman, Richard E.; Slep, Amy M. Smith
2011-01-01
Objective: Hazardous drinking is a serious societal concern in military populations. Efforts to reduce hazardous drinking among military personnel have been limited in effectiveness. There is a need for a deeper understanding of how community-based prevention models apply to hazardous drinking in the military. Community-wide prevention efforts may…
49 CFR 171.1 - Applicability of Hazardous Materials Regulations (HMR) to persons and functions.
Code of Federal Regulations, 2013 CFR
2013-10-01
... package or container or on a package or container containing a residue of a hazardous material. (5... bracing a hazardous materials package in a freight container or transport vehicle. (13) Segregating a hazardous materials package in a freight container or transport vehicle from incompatible cargo. (14...
49 CFR 171.1 - Applicability of Hazardous Materials Regulations (HMR) to persons and functions.
Code of Federal Regulations, 2011 CFR
2011-10-01
... package or container or on a package or container containing a residue of a hazardous material. (5... bracing a hazardous materials package in a freight container or transport vehicle. (13) Segregating a hazardous materials package in a freight container or transport vehicle from incompatible cargo. (14...
49 CFR 171.1 - Applicability of Hazardous Materials Regulations (HMR) to persons and functions.
Code of Federal Regulations, 2010 CFR
2010-10-01
... package or container or on a package or container containing a residue of a hazardous material. (5... bracing a hazardous materials package in a freight container or transport vehicle. (13) Segregating a hazardous materials package in a freight container or transport vehicle from incompatible cargo. (14...
49 CFR 171.1 - Applicability of Hazardous Materials Regulations (HMR) to persons and functions.
Code of Federal Regulations, 2012 CFR
2012-10-01
... package or container or on a package or container containing a residue of a hazardous material. (5... bracing a hazardous materials package in a freight container or transport vehicle. (13) Segregating a hazardous materials package in a freight container or transport vehicle from incompatible cargo. (14...
Hazard recognition in mining: A psychological perspective. Information circular/1995
DOE Office of Scientific and Technical Information (OSTI.GOV)
Perdue, C.W.; Kowalski, K.M.; Barrett, E.A.
1995-07-01
This U.S. Bureau of Mines report considers, from a psychological perspective, the perceptual process by which miners recognize and respond to mining hazards. It proposes that if the hazard recognition skills of miners can be improved, mining accidents may be reduced to a significant degree. Prior studies of hazard perception in mining are considered, as are relevant studies from investigations of military target identification, pilot and gunnery officer training, transportation safety, automobile operator behavior, as well as research into sensory functioning and visual information processing. A general model of hazard perception is introduced, and selected concepts from the psychology ofmore » perception that are applicable to the detection of mining hazards are reviewed. Hazard recognition is discussed as a function of the perceptual cues available to the miner as well as the cognitive resources and strategies employed by the miner. The development of expertise in resonding to hazards is related to individual differences in the experience, aptitude, and personality of the worker. Potential applications to miner safety and training are presented.« less
Kucharska-Newton, Anna M.; Rosamond, Wayne D.; Schroeder, Jane C.; McNeill, Ann Marie; Coresh, Josef; Folsom, Aaron R.
2008-01-01
Summary This study examined prospectively the association of baseline plasma HDL-cholesterol levels with incidence of lung cancer in 14, 547 members of the Atherosclerosis Risk in Communities (ARIC) cohort. There were 259 cases of incident lung cancer identified during follow-up from 1987 through 2000. Results of this study indicated a relatively weak inverse association of HDL-cholesterol with lung cancer that was dependent on smoking status. The hazard ratio of lung cancer incidence in relation to low HDL-cholesterol, adjusted for race, gender, exercise, alcohol consumption, body mass index, triglycerides, age, and cigarette pack-years of smoking, was 1.45 (95% confidence interval 1.10, 1.92). This association was observed among former smokers (hazard ratio: 1.77, 95% confidence interval 1.05, 2.97), but not current smokers. The number of cases among never smokers in this study was too small (n=13) for meaningful interpretation of effect estimates. Excluding cases occurring within five years of baseline did not appreciably change the point estimates, suggesting lack of reverse causality. The modest association of low plasma HDL-cholesterol with greater incident lung cancer observed in this study is in agreement with existing case-control studies. PMID:18342390
Jones, Jeffrey A; Fayad, Luis E; Elting, Linda S; Rodriguez, Maria A
2010-09-01
We conducted a retrospective cohort study examining the influence of obesity on treatment outcome and survival among 712 patients with intermediate-grade B-cell NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was approximated by body mass index categorized according to the World Health Organization schema. Logistic and Cox proportional hazards regression modeling was used to adjust for baseline patient demographic, disease, and treatment variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30 kg/m(2)) and more than 23% were obese (BMI >or= 30 kg/m(2)). Risk factors were similar across groups and treatment intensity did not vary by BMI. Median follow-up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for other significant prognostic factors, BMI in the overweight range was associated with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR 0.74, p = 0.030). Increased BMI is associated with significantly improved survival among patients with treatment-naive, intermediate-grade B-cell NHL. Prospective confirmation of these results is warranted given the increasing prevalence of both NHL and obesity.
Merkel, C; Gatta, A; Bellumat, A; Bolognesi, M; Borsato, L; Caregaro, L; Cavallarin, G; Cielo, R; Cristina, P; Cucci, E; Donada, C; Donadon, V; Enzo, E; Martin, R; Mazzaro, C; Sacerdoti, D; Torboli, P
1996-01-01
To identify the best time-frame for defining bleeding-related death after variceal bleeding in patients with cirrhosis. Prospective long-term evaluation of a cohort of 155 patients admitted with variceal bleeding. Eight medical departments in seven hospitals in north-eastern Italy. Non-linear regression analysis of a hazard curve for death, and Cox's multiple regression analyses using different zero-time points. Cumulative hazard plots gave two slopes, the first corresponding to the risk of death from acute bleeding, the second a baseline risk of death. The first 30 days were outside the confidence limits of the regression curve for the baseline risk of death. Using Cox's regression analysis, the significant predictors of overall mortality risk were balanced between factors related to severity of bleeding and those related to severity of liver disease. If only deaths occurring after 30 days were considered, only predictors related to the severity of liver disease were found to be of importance. Thirty days after bleeding is considered to be a reasonable time-frame for the definition of bleeding-related death in patients with cirrhosis and variceal bleeding.
Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen; Gasse, Christiane
2017-11-01
Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. We conducted a population-based follow-up study among individuals with a first-time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received at least 2 prior antipsychotic monotherapy trials of adequate duration. We used adjusted Cox regression analysis to calculate hazard ratios. We identified 390 individuals with a C-reactive protein measurement at first-time schizophrenia diagnosis. A nonsignificant higher median C-reactive protein (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). C-reactive protein, as a single inflammatory marker, appears insufficient to detect treatment-resistant schizophrenia. Copyright © 2017 John Wiley & Sons, Ltd.
The effects of practice with MP3 players on driving performance.
Chisholm, S L; Caird, J K; Lockhart, J
2008-03-01
This study examined the effects of repeated iPod interactions on driver performance to determine if performance decrements decreased with practice. Nineteen younger drivers (mean age=19.4, range 18-22) participated in a seven session study in the University of Calgary Driving Simulator (UCDS). Drivers encountered a number of critical events on the roadways while interacting with an iPod including a pedestrian entering the roadway, a vehicle pullout, and a lead vehicle braking. Measures of hazard response, vehicle control, eye movements, and secondary task performance were analyzed. Increases in perception response time (PRT) and collisions were found while drivers were performing the difficult iPod tasks, which involved finding a specific song within the song titles menu. Over the course of the six experimental sessions, driving performance improved in all conditions. Difficult iPod interactions significantly increased the amount of visual attention directed into the vehicle above that of the baseline condition. With practice, slowed responses to driving hazards while interacting with the iPod declined somewhat, but a decrement still remained relative to the baseline condition. The multivariate results suggest that access to difficult iPod tasks while vehicles are in motion should be curtailed.
A prospective study of sudden unexpected infant death after reported maltreatment.
Putnam-Hornstein, Emily; Schneiderman, Janet U; Cleves, Mario A; Magruder, Joseph; Krous, Henry F
2014-01-01
To examine whether infants reported for maltreatment face a heightened risk of sudden infant death syndrome (SIDS) and other leading causes of sudden unexpected infant death (SUID). Linked birth and infant death records for all children born in California between 1999 and 2006 were matched to administrative child protection data. Infants were prospectively followed from birth through death or 1 year of age. A report of maltreatment was modeled as a time-varying covariate; risk factors at birth were included as baseline covariates. Multivariable competing risk survival models were used to estimate the adjusted relative hazard of postneonatal SIDS and other SUID. A previous maltreatment report emerged as a significant predictor of SIDS and other SUID. After adjusting for baseline risk factors, the rate of SIDS was more than 3 times as great among infants reported for possible maltreatment (hazard ratio: 3.22; 95% CI: 2.66, 3.89). Infants reported to child protective services have a heightened risk of SIDS and other SUID. Targeted services and improved communication between child protective services and the pediatric health care community may enhance infant well-being and reduce risk of death. Copyright © 2014 Mosby, Inc. All rights reserved.
Prognostic Value of Adipokines in Predicting Cardiovascular Outcome: Explaining the Obesity Paradox.
Wolk, Robert; Bertolet, Marnie; Singh, Prachi; Brooks, Maria M; Pratley, Richard E; Frye, Robert L; Mooradian, Arshag D; Rutter, Martin K; Calvin, Andrew D; Chaitman, Bernard R; Somers, Virend K
2016-07-01
To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008). In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005). Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox." clinicaltrials.gov Identifier: NCT00006305. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Heymans, Martijn W; de Vet, Henrica C W; Bongers, Paulien M; Knol, Dirk L; Koes, Bart W; van Mechelen, Willem
2006-05-01
Randomized controlled trial. To compare high- and low-intensity back schools with usual care in occupational health care. The content and intensity of back schools vary widely and the methodologic quality of randomized controlled trials is generally weak. Until now, no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain. Workers (n = 299) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and randomly assigned to a high-intensity back school, a low-intensity back school, or care as usual. Outcome measures were days until return to work, total days of sick-leave, pain, functional status, kinesiophobia, and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up. Principal analyses were performed according to the intention-to-treat principle. We randomly allocated 299 workers. Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school, with hazard ratios of 1.4 (P = 0.06) and 1.3 (P = 0.09), respectively. The comparison between high-intensity back school and usual care resulted in a hazard ratio of 1.0 (P = 0.83). The median number of sick-leave days was 68, 75, and 85 in the low-intensity back school, usual care, and high-intensity back school, respectively. Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school. No substantial differences on pain and perceived recovery were found between groups. The low-intensity back school was most effective in reducing work absence, functional disability, and kinesiophobia, and more workers in this group scored a higher perceived recovery during the 6-month follow-up.
Brisco, Meredith A; Coca, Steven G; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D; Kimmel, Stephen E; Testani, Jeffrey M
2013-03-01
Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.
Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.
2014-01-01
Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.
Ridker, Paul M; Revkin, James; Amarenco, Pierre; Brunell, Robert; Curto, Madelyn; Civeira, Fernando; Flather, Marcus; Glynn, Robert J; Gregoire, Jean; Jukema, J Wouter; Karpov, Yuri; Kastelein, John J P; Koenig, Wolfgang; Lorenzatti, Alberto; Manga, Pravin; Masiukiewicz, Urszula; Miller, Michael; Mosterd, Arend; Murin, Jan; Nicolau, Jose C; Nissen, Steven; Ponikowski, Piotr; Santos, Raul D; Schwartz, Pamela F; Soran, Handrean; White, Harvey; Wright, R Scott; Vrablik, Michal; Yunis, Carla; Shear, Charles L; Tardif, Jean-Claude
2017-04-20
Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389 .).
NASA Astrophysics Data System (ADS)
Schoessow, F. S.; Li, Y.; Howe, P. D.
2016-12-01
Extreme heat events are the deadliest natural hazard in the United States and are expected to increase in both severity and frequency in the coming years due to the effects of climate change. The risks of climate change and weather-related events such as heat waves to a population can be more comprehensively assessed by coupling the traditional examination of natural hazards using remote sensing and geospatial analysis techniques with human vulnerability factors and individual perceptions of hazards. By analyzing remote-sensed and empirical survey data alongside national hazards advisories, this study endeavors to establish a nationally-representative baseline quantifying the spatiotemporal variation of individual heat vulnerabilities at multiple scales and between disparate population groups affected by their unique socioenvironmental factors. This is of immediate academic interest because the study of heat waves risk perceptions remains relatively unexplored - despite the intensification of extreme heat events. The use of "human sensors", georeferenced & timestamped individual response data, provides invaluable contextualized data at a high spatial resolution, which will enable policy-makers to more effectively implement targeted strategies for risk prevention, mitigation, and communication. As climate change risks are further defined, this cognizance will help identify vulnerable populations and enhance national hazard preparedness and recovery frameworks.
Emergency Response Capability Baseline Needs Assessment Compliance Assessment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sharry, John A.
2013-09-16
This document is the second of a two-part analysis of Emergency Response Capabilities of Lawrence Livermore National Laboratory. The first part, 2013 Baseline Needs Assessment Requirements Document established the minimum performance criteria necessary to meet mandatory requirements. This second part analyses the performance of Lawrence Livermore Laboratory Emergency Management Department to the contents of the Requirements Document. The document was prepared based on an extensive review of information contained in the 2009 BNA, the 2012 BNA document, a review of Emergency Planning Hazards Assessments, a review of building construction, occupancy, fire protection features, dispatch records, LLNL alarm system records, firemore » department training records, and fire department policies and procedures.« less
Chang, Chia-Lin; Munin, Michael C.; Skidmore, Elizabeth R.; Niyonkuru, Christian; Huber, Lynne M.; Weber, Douglas J.
2015-01-01
Objective To determine whether baseline hand spastic hemiparesis assessed by the Chedoke-McMaster Assessment influences functional improvement after botulinum toxin type A (BTX-A) injections and postinjection therapy. Design Prospective cohort study. Setting Outpatient spasticity clinic. Participants Participants (N = 14) with spastic hemiparesis divided into 2 groups: Chedoke-McMaster Assessment Hand-Higher Function (stage≥4, n = 5) and Chedoke-McMaster Assessment Hand-Lower Function (stage = 2 or 3, n = 9). Interventions Upper-limb BTX-A injections followed by 6 weeks of postinjection therapy. Main Outcome Measures Primary outcomes were Motor Activity Log-28 and Motor Activity Log items. Secondary outcomes were Action Research Arm Test (ARAT), Motor Activity Log-Self-Report, and Modified Ashworth Scale (MAS). Measures were assessed at baseline (preinjection), 6 weeks, 9 weeks, and 12 weeks postinjection. Results Primary and secondary outcomes improved significantly over time in both groups. Although no significant differences in ARAT or MAS change scores were noted between groups, Chedoke-McMaster Assessment Hand-Higher Function group demonstrated greater change on Motor Activity Log-28 (P = .013) from baseline to 6 weeks and Motor Activity Log items (P = .006) from baseline to 12 weeks compared to Chedoke-McMaster Assessment Hand-Lower Function group. Conclusions BTX-A injections and postinjection therapy improved hand function and reduced spasticity for both Chedoke-McMaster Assessment Hand-Higher Function and Chedoke-McMaster Assessment Hand-Lower Function groups. Clinicians should expect to see larger gains for persons with less baseline impairment. PMID:19735772
Apostolidou, Ioanna; Morrissette, Greg; Sarwar, Muhammad F; Konia, Mojca R; Kshettry, Vibhu R; Wahr, Joyce A; Lobbestael, Aaron A; Nussmeier, Nancy A
2012-12-01
This "real-world" study was designed to assess the patterns of regional cerebral oxygen saturation (rSO(2)) change during adult cardiac surgery. A secondary objective was to determine any relation between perioperative rSO(2) (baseline and during surgery) and patient characteristics or intraoperative variables. Prospective, observational, multicenter, nonrandomized clinical study. Cardiac operating rooms at 3 academic medical centers. Ninety consecutive adult patients presenting for cardiac surgery with or without cardiopulmonary bypass. Patients received standard care at each institution plus bilateral forehead recordings of cerebral oxygen saturation with the 7600 Regional Oximeter System (Nonin Medical, Plymouth, MN). The average baseline (before induction) rSO(2) was 63.9 ± 8.8% (range 41%-95%); preoperative hematocrit correlated with baseline rSO(2) (0.48% increase for each 1% increase in hematocrit, p = 0.008). The average nadir (lowest recorded rSO(2) for any given patient) was 54.9 ± 6.6% and was correlated with on-pump surgery, baseline rSO(2), and height. Baseline rSO(2) was found to be an independent predictor of length of stay (hazard ratio 1.044, confidence interval 1.02-1.07, for each percentage of baseline rSO(2)). In cardiac surgical patients, lower baseline rSO(2) value, on-pump surgery, and height were significant predictors of nadir rSO(2), whereas only baseline rSO(2) was a predictor of postoperative length of stay. These findings support previous research on the predictive value of baseline rSO(2) on length of stay and emphasize the need for further research regarding the clinical relevance of baseline rSO(2) and intraoperative changes. Copyright © 2012 Elsevier Inc. All rights reserved.
Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial.
Moe, Sharon M; Abdalla, Safa; Chertow, Glenn M; Parfrey, Patrick S; Block, Geoffrey A; Correa-Rotter, Ricardo; Floege, Jürgen; Herzog, Charles A; London, Gerard M; Mahaffey, Kenneth W; Wheeler, David C; Dehmel, Bastian; Goodman, William G; Drüeke, Tilman B
2015-06-01
Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%. Copyright © 2015 by the American Society of Nephrology.