The episodic random utility model unifies time trade-off and discrete choice approaches in health state valuation

ABSTRACT: BACKGROUND: To present an episodic random utility model that unifies time trade-off and discrete choice approaches in health state valuation. METHODS: First, we introduce two alternative random utility models (RUMs) for health preferences: the episodic RUM and the more common instant RUM. For the interpretation of time trade-off (TTO) responses, we show that the episodic model implies a coefficient estimator, and the instant model implies a mean slope estimator. Secondly, we demonstrate these estimators and the differences between the estimates for 42 health states using TTO responses from the seminal Measurement and Valuation in Health (MVH) study conducted in the United Kingdom. Mean slopes are estimates with and without Dolan's transformation of worse-than-death (WTD) responses. Finally, we demonstrate an exploded probit estimator, an extension of the coefficient estimator for discrete choice data that accommodates both TTO and rank responses. RESULTS: By construction, mean slopes are less than or equal to coefficients, because slopes are fractions and, therefore, magnify downward errors in WTD responses. The Dolan transformation of WTD responses causes mean slopes to increase in similarity to coefficient estimates, yet they are not equivalent (i.e., absolute mean difference = 0.179). Unlike mean slopes, coefficient estimates demonstrate strong concordance with rank-based predictions (Lin's rho = 0.91). Combining TTO and rank responses under the exploded probit model improves the identification of health state values, decreasing the average width of confidence intervals from 0.057 to 0.041 compared to TTO only results. CONCLUSION: The episodic RUM expands upon the theo

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

A Comparison of Three Methods of Mendelian Randomization when the Genetic Instrument, the Risk Factor and the Outcome Are All Binary

The method of instrumental variable (referred to as Mendelian randomization when the instrument is a genetic variant) has been initially developed to infer on a causal effect of a risk factor on some outcome of interest in a linear model. Adapting this method to nonlinear models, however, is known to be problematic. In this paper, we consider the simple case when the genetic instrument, the risk factor, and the outcome are all binary. We compare via simulations the usual two-stages estimate of a causal odds-ratio and its adjusted version with a recently proposed estimate in the context of a clinical trial with noncompliance. In contrast to the former two, we confirm that the latter is (under some conditions) a valid estimate of a causal odds-ratio defined in the subpopulation of compliers, and we propose its use in the context of Mendelian randomization. By analogy with a clinical trial with noncompliance, compliers are those individuals for whom the presence/absence of the risk factor X is determined by the presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z whatever the alleles randomly received at conception). We also recall and illustrate the huge variability of instrumental variable estimates when the instrument is weak (i.e., with a low percentage of compliers, as is typically the case with genetic instruments for which this proportion is frequently smaller than 10%) where the inter-quartile range of our simulated estimates was up to 18 times higher compared to a conventional (e.g., intention-to-treat) approach. We thus conclude that the need to find stronger instruments is probably as important as the need to develop a methodology allowing to consistently estimate a causal odds-ratio

NIH Disease Funding Levels and Burden of Disease

BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Unexpected Course of Nonlinear Cardiac Interbeat Interval Dynamics during Childhood and Adolescence

The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10−4 to 10−2 Hz) intermediate-term (DFA, detrended fluctuation analysis, α2) and short-term (DFA α1). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: −1.06 vs. −1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α1 and α2 increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty

Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers

<p>Abstract</p> <p>Background</p> <p>Previous studies on the effects of Statins in preventing atrial fibrillation (AF) after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown.</p> <p>Methods</p> <p>We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG) (n = 1493) or valve surgery (n = 443) at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively).</p> <p>Results</p> <p>Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30%) patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p < 0.0001). Patients with a past history of AF had a 5 times higher risk of postoperative AF (odds ratio 5.1; 95% confidence interval 3.4 to 7.7; p < 0.0001). AF occurred in 31% of patients taking statins versus 29% of the others (p = 0.49). In multivariable analysis, statins were not associated with AF (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.7 to 1.2; p = 0.59). However, in a subgroup analysis, the patients treated with Simvastatin >20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03) in comparison to those taking lower dosages.</p> <p>Conclusion</p> <p>Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages</p

Virtual Reality as a Tool for Evaluation of Repetitive Rhythmic Movements in the Elderly and Parkinson's Disease Patients

This work presents an immersive Virtual Reality (VR) system to evaluate, and potentially treat, the alterations in rhythmic hand movements seen in Parkinson's disease (PD) and the elderly (EC), by comparison with healthy young controls (YC). The system integrates the subjects into a VR environment by means of a Head Mounted Display, such that subjects perceive themselves in a virtual world consisting of a table within a room. In this experiment, subjects are presented in 1st person perspective, so that the avatar reproduces finger tapping movements performed by the subjects. The task, known as the finger tapping test (FT), was performed by all three subject groups, PD, EC and YC. FT was carried out by each subject on two different days (sessions), one week apart. In each FT session all subjects performed FT in the real world (FTREAL) and in the VR (FTVR); each mode was repeated three times in randomized order. During FT both the tapping frequency and the coefficient of variation of inter-tap interval were registered. FTVR was a valid test to detect differences in rhythm formation between the three groups. Intra-class correlation coefficients (ICC) and mean difference between days for FTVR (for each group) showed reliable results. Finally, the analysis of ICC and mean difference between FTVR vs FTREAL, for each variable and group, also showed high reliability. This shows that FT evaluation in VR environments is valid as real world alternative, as VR evaluation did not distort movement execution and detects alteration in rhythm formation. These results support the use of VR as a promising tool to study alterations and the control of movement in different subject groups in unusual environments, such as during fMRI or other imaging studies