Sharing clinical information across care settings: the birth of an integrated assessment system

Background: Population ageing, the emergence of chronic illness, and the shift away from institutional care challenge conventional approaches to assessment systems which traditionally are problem and setting specific

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Temporal and Geographic variation in the validity and internal consistency of the Nursing Home Resident Assessment Minimum Data Set 2.0

<p>Abstract</p> <p>Background</p> <p>The Minimum Data Set (MDS) for nursing home resident assessment has been required in all U.S. nursing homes since 1990 and has been universally computerized since 1998. Initially intended to structure clinical care planning, uses of the MDS expanded to include policy applications such as case-mix reimbursement, quality monitoring and research. The purpose of this paper is to summarize a series of analyses examining the internal consistency and predictive validity of the MDS data as used in the "real world" in all U.S. nursing homes between 1999 and 2007.</p> <p>Methods</p> <p>We used person level linked MDS and Medicare denominator and all institutional claim files including inpatient (hospital and skilled nursing facilities) for all Medicare fee-for-service beneficiaries entering U.S. nursing homes during the period 1999 to 2007. We calculated the sensitivity and positive predictive value (PPV) of diagnoses taken from Medicare hospital claims and from the MDS among all new admissions from hospitals to nursing homes and the internal consistency (alpha reliability) of pairs of items within the MDS that logically should be related. We also tested the internal consistency of commonly used MDS based multi-item scales and examined the predictive validity of an MDS based severity measure viz. one year survival. Finally, we examined the correspondence of the MDS discharge record to hospitalizations and deaths seen in Medicare claims, and the completeness of MDS assessments upon skilled nursing facility (SNF) admission.</p> <p>Results</p> <p>Each year there were some 800,000 new admissions directly from hospital to US nursing homes and some 900,000 uninterrupted SNF stays. Comparing Medicare enrollment records and claims with MDS records revealed reasonably good correspondence that improved over time (by 2006 only 3% of deaths had no MDS discharge record, only 5% of SNF stays had no MDS, but over 20% of MDS discharges indicating hospitalization had no associated Medicare claim). The PPV and sensitivity levels of Medicare hospital diagnoses and MDS based diagnoses were between .6 and .7 for major diagnoses like CHF, hypertension, diabetes. Internal consistency, as measured by PPV, of the MDS ADL items with other MDS items measuring impairments and symptoms exceeded .9. The Activities of Daily Living (ADL) long form summary scale achieved an alpha inter-consistency level exceeding .85 and multi-item scale alpha levels of .65 were achieved for well being and mood, and .55 for behavior, levels that were sustained even after stratification by ADL and cognition. The Changes in Health, End-stage disease and Symptoms and Signs (CHESS) index, a summary measure of frailty was highly predictive of one year survival.</p> <p>Conclusion</p> <p>The MDS demonstrates a reasonable level of consistency both in terms of how well MDS diagnoses correspond to hospital discharge diagnoses and in terms of the internal consistency of functioning and behavioral items. The level of alpha reliability and validity demonstrated by the scales suggest that the data can be useful for research and policy analysis. However, while improving, the MDS discharge tracking record should still not be used to indicate Medicare hospitalizations or mortality. It will be important to monitor the performance of the MDS 3.0 with respect to consistency, reliability and validity now that it has replaced version 2.0, using these results as a baseline that should be exceeded.</p

Gene-based multiple trait analysis for exome sequencing data

The common genetic variants identified through genome-wide association studies explain only a small proportion of the genetic risk for complex diseases. The advancement of next-generation sequencing technologies has enabled the detection of rare variants that are expected to contribute significantly to the missing heritability. Some genetic association studies provide multiple correlated traits for analysis. Multiple trait analysis has the potential to improve the power to detect pleiotropic genetic variants that influence multiple traits. We propose a gene-level association test for multiple traits that accounts for correlation among the traits. Gene- or region-level testing for association involves both common and rare variants. Statistical tests for common variants may have limited power for individual rare variants because of their low frequency and multiple testing issues. To address these concerns, we use the weighted-sum pooling method to test the joint association of multiple rare and common variants within a gene. The proposed method is applied to the Genetic Association Workshop 17 (GAW17) simulated mini-exome data to analyze multiple traits. Because of the nature of the GAW17 simulation model, increased power was not observed for multiple-trait analysis compared to single-trait analysis. However, multiple-trait analysis did not result in a substantial loss of power because of the testing of multiple traits. We conclude that this method would be useful for identifying pleiotropic genes

Maternal hormone levels among populations at high and low risk of testicular germ cell cancer

Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol (total, free and bioavailable), estriol, testosterone (total, free and bioavailable), sex hormone binding globulin (SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester (P=0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones (estradiol/testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk

Classification of fibroglandular tissue distribution in the breast based on radiotherapy planning CT

Accurate segmentation of breast tissues is required for a number of applications such as model based deformable registration in breast radiotherapy. The accuracy of breast tissue segmentation is affected by the spatial distribution (or pattern) of fibroglandular tissue (FT). The goal of this study was to develop and evaluate texture features, determined from planning computed tomography (CT) data, to classify the spatial distribution of FT in the breas

A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program.</p> <p>Methods/Design</p> <p>The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64–80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects.</p> <p>Discussion</p> <p>This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life.</p

Cocoa flavanols adjuvant to an oral nutritional supplement acutely enhances nutritive flow in skeletal muscle without altering leg glucose uptake kinetics in older adults

This is the final version. Available on open access from MDPI via the DOI in this record. Data Availability Statement: The data presented in this study are available on request from the corresponding authors.Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.Abbott NutritionMedical Research Council (MRC)National Institute for Health Research (NIHR

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin