Registry based analysis of cost-of-illness study among stage C heart failure patients at Hospital Queen Elizabeth II,Sabah, Malaysia

Background

Numerous cost-of-illness studies of heart failure (HF) have been published in developed countries, but such knowledge is lacking in Malaysia. To fill the gap, this study estimated the cost of HF in Hospital Queen Elizabeth II (HQEII).

Towards a Theoretical Background for Strong-Scattering Inversion – Direct Envelope Inversion and Gel'fand-Levitan-Marchenko Theory

Strong-scattering inversion or the inverse problem for strong scattering has different physical-mathematical foundations from the weak-scattering case. Seismic inversion based on wave equation for strong scattering cannot be directly solved by Newton's local optimization method which is based on weak-nonlinear assumption. Here I try to illustrate the connection between the Schrödinger inverse scattering (inverse problem for Schrödinger equation) by GLM (Gel'fand-Levitan-Marchenko) theory and the direct envelope inversion (DEI) using reflection data. The difference between wave equation and Schrödinger equation is that the latter has a potential independent of frequency while the former has a frequency-square dependency in the potential. I also point out that the traditional GLM equation for potential inversion can only recover the high-wavenumber components of impedance profile. I propose to use the Schrödinger impedance equation for direct impedance inversion and introduce a singular impedance function which also corresponds to a singular potential for the reconstruction of impedance profile, including discontinuities and long-wavelength velocity structure. I will review the GLM theory and its application to impedance inversion including some numerical examples. Then I analyze the recently developed multiscale direct envelope inversion (MS-DEI) and its connection to the inverse Schrödinger scattering. It is conceivable that the combination of strong-scattering inversion (inverse Schrödinger scattering) and weak-scattering inversion (local optimization based inversion) may create some inversion methods working for a whole range of inversion problems in geophysical exploration.     

Recovery of original individual person data (IPD) inferences from empirical IPD summaries only: Applications to distributed computing under disclosure constraints

There are many settings where individual person data (IPD) are not available, due to privacy or technical reasons, and one must work with IPD proxies, such as summary statistics, to approximate original IPD inferences, that is, the results of statistical analyses that would ideally have been performed on individual-level data. For instance, in a distributed computing setting, as implemented in the DataSHIELD software framework, different centers can only share IPD proxies to obtain pooled IPD inferences. Such privacy requirements limit the scope of statistical investigation. For example, it can be challenging to perform between-center random-effect regression models. To increase modeling freedom we propose a method that only uses simple nondisclosive summaries of the original IPD as input, such as empirical marginal moments and correlation matrices, and generates artificial data compatible with those summary features. Specifically, data are generated from a Gaussian copula with marginal and joint components specified by the above summaries. The goal is to reproduce original IPD features in the artificial data, such that original IPD inferences are recovered from the artificial data. In an application example, and through simulations, we show that we can recover estimates of a multivariable IPD random-effect logistic regression, from artificial data generated via the Gaussian copula using the above IPD summaries, suggesting the proposed approach provides a generally applicable strategy for distributed computing settings with data protection constraints.     

High test–retest reliability of checkerboard reversal visual evoked potentials (VEP) over 8 months

ObjectiveThe inter-individual variation in the shape of a visual evoked potential (VEP) is large even for simple stimuli. We compared the inter-individual variation in VEP waveform to the intra-individual stability.MethodsWe recorded VEP with checkerboard stimulation in 10 women aged 19–29 years in two sessions. We determined the latencies and the peak-to-peak amplitude of N75 and P100. As a new approach in VEP research, we regressed VEP waveforms pairwise onto each other and calculated a t-value between all sessions. The maximal t-value was taken to indicate recognition for all 19 comparisons performed with one session. The recognition rate was cross-validated in a generalized linear regression model (GLM).ResultsThe number of sessions correctly matched to the correct subject was 19 of 20 (true positives) leading to a sensitivity of 95.0% with confidence interval [75.1% 99.9%] for the method. The number of true negatives was 359 of 360 leading to a specificity of 99.7% [98.5% 100.0%].ConclusionsThe VEP waveform shows high intra-individual stability compared to the inter-individual variation in healthy women.SignificanceWith a new statistical approach the effect of external factors on the VEP waveform can now be contrasted against the normal variability over time in longitudinal studies.     

Noninvasive classification of hepatic fibrosis based on texture parameters from double contrast‐enhanced magnetic resonance images

Purpose:

To demonstrate a proof of concept that quantitative texture feature analysis of double contrast‐enhanced magnetic resonance imaging (MRI) can classify fibrosis noninvasively, using histology as a reference standard.

Materials and Methods:

A Health Insurance Portability and Accountability Act (HIPAA)‐compliant Institutional Review Board (IRB)‐approved retrospective study of 68 patients with diffuse liver disease was performed at a tertiary liver center. All patients underwent double contrast‐enhanced MRI, with histopathology‐based staging of fibrosis obtained within 12 months of imaging. The MaZda software program was used to compute 279 texture parameters for each image. A statistical regularization technique, generalized linear model (GLM)‐path, was used to develop a model based on texture features for dichotomous classification of fibrosis category (F ≤2 vs. F ≥3) of the 68 patients, with histology as the reference standard. The model's performance was assessed and cross‐validated. There was no additional validation performed on an independent cohort.

Results:

Cross‐validated sensitivity, specificity, and total accuracy of the texture feature model in classifying fibrosis were 91.9%, 83.9%, and 88.2%, respectively.

Conclusion:

This study shows proof of concept that accurate, noninvasive classification of liver fibrosis is possible by applying quantitative texture analysis to double contrast‐enhanced MRI. Further studies are needed in independent cohorts of subjects. J. Magn. Reson. Imaging 2012;36:1154–1161. © 2012 Wiley Periodicals, Inc.     

Comparison of BOLD and direct‐MR neuronal detection (DND) in the human visual cortex at 3T

Direct‐MR neuronal detection (DND) of transient magnetic fields has recently been investigated as a novel imaging alternative to the conventional BOLD functional MRI (fMRI) technique. However, there remain controversial issues and debate surrounding this methodology, and this study attempts clarification by comparing BOLD responses in the human visual system with those of DND. BOLD relies on indirectly measuring blood oxygenation and flow changes as a result of neuronal activity, whereas the putative DND method is based on the hypothesis that the components of the in vivo neuronal magnetic fields, which lie parallel to the B₀ field, can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. Block paradigms of checkerboard patterns were used for visual stimulation in both DND and BOLD experiments, allowing detection based on different frequency responses. This study shows colocalization of some voxels with slow BOLD responses and putative fast DND responses using General Linear Model (GLM) analysis. Frequency spectra for the activated voxel cluster are also shown for both stimulated and control data. The mean percentage signal change for the DND responses is 0.2%, corresponding to a predicted neuronal field of 0.14 nT. Magn Reson Med 60:1147–1154, 2008. © 2008 Wiley‐Liss, Inc.     

Economic analysis of recombinant activated factor VII versus plasma-derived activated prothrombin complex concentrate in mild to moderate bleeds: haemophilia registry data from the Czech Republic

Introduction

Several studies suggest that recombinant activated factor VII (rFVIIa) is more cost-effective than plasma-derived activated prothrombin complex concentrate (pd-aPCC) in haemophilia with inhibitors. However, most do not consider differences between treated patients. This study compared the pharmacoeconomics of rFVIIa versus pd-aPCC treatment of mild to moderate bleeds in inhibitor patients, taking co-variables into account.

Methods

The HemoRec and HemIS registries capture exhaustive bleeding data in inhibitor patients in the Czech Republic. For each bleed, patient and bleed characteristics, treatment outcomes and bypassing agent use were retrospectively analysed, and direct costs of care per bleed calculated. Generalised Linear Model regression methods with cluster effect were employed to account for the possibility of several bleedings from the same patient.

Results

There were 108 and 53 mild to moderate bleeds in the rFVIIa and pd-aPCC groups, respectively. Although re-bleeding rates were similar in both groups, deeper analyses revealed significant differences in time to bleed resolution: 93.8% of bleeds treated with rFVIIa were resolved within ≤ 12 h, versus 60.4% with pd-aPCC (P < 0.001). Mean total cost/bleed was lower with rFVIIa (336,852 [median, 290,696] CZK; €12,760 [11,011]) than pd-aPCC (522,768 [341,310] CZK; €19,802 [12,928]) (P = 0.002). Results were maintained after controlling for potential co-variables (bleed nature, time to treatment, target joints).

Conclusions

The lower total treatment costs per bleed with rFVIIa than pd-aPCC suggest that first-line rFVIIa is more cost-effective than pd-aPCC in mild to moderate bleeds. Time to bleed resolution was also significantly shorter with rFVIIa. These results were maintained when controlled for potential confounders.     

Association of genetic polymorphisms of RANK,RANKL and OPG with bone mineral density in Chinese peri- and postmenopausal women

Objectives

To explore the influence of 14 single nucleotide polymorphisms (SNPs) in receptor activator of nuclear factor-kappa B (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) on bone mineral density (BMD) in a Chinese female population.

Design and methods

A cross-sectional study was conducted in 108 perimenopausal and 127 postmenopausal women aged 43–65 years. All participants underwent lumbar spinal and nondominant femoral BMD evaluation by dual energy X-ray absorptiometry. Fourteen RANK, RANKL and OPG genotypes were determined by chip-based MALDI-TOF mass spectrometry. The differences between the BMDs of the RANK genotypes were analyzed.

Results

Five SNPs (rs6993813, rs4355801, rs1032129 and rs2073618 in OPG and rs3018362 in RANK) were significantly associated with BMD or with BMD adjusted for body weight or years since menopause, mostly at the femoral neck but also partly at the total hip (p < 0.05). The risk allele frequencies observed in our sample were different from those found in Europeans but the effects of these risk alleles on BMD values had the same direction in our cohort as in Europeans, except for rs3018362 with G as the risk allele, which was contrary to other studies. None of the SNPs in RANKL were associated with BMD at any anatomical site.

Conclusions

Our findings suggest that OPG and RANK but not RANKL genetic polymorphisms influence BMD mainly in the femoral neck in peri- and postmenopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.     

Dose-Time-Response Modeling Using Negative Binomial Distribution

People exposed to certain diseases are required to be treated with a safe and effective dose level of a drug. In epidemiological studies to find out an effective dose level, different dose levels are applied to the exposed and a certain number of cures is observed. Negative binomial distribution is considered to fit overdispersed Poisson count data. This study investigates the time effect on the response at different time points as well as at different dose levels. The point estimation and confidence bands for ED _100p (t) and LT _100p (d) are formulated in closed form for the proposed dose-time-response model with the negative binomial distribution. Numerical illustrations are carried out in order to check the performance level of the proposed model.