A markov model to evaluate hospital readmission

<p>Abstract</p> <p>Background</p> <p>The analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF).</p> <p>Methods</p> <p>The Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998–2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis.</p> <p>Results</p> <p>The probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission.</p> <p>Conclusion</p> <p>The time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission.</p

Accuracy and reproducibility of right ventricular quantification in patients with pressure and volume overload using single-beat three-dimensional echocardiography.

The right ventricle is a complex structure that is challenging to quantify by two-dimensional (2D) echocardiography. Unlike disk summation three-dimensional (3D) echocardiography (3DE), single-beat 3DE can acquire large volumes at high volume rates in one cardiac cycle, avoiding stitching artifacts or long breath-holds. The aim of this study was to assess the accuracy and test-retest reproducibility of single-beat 3DE for quantifying right ventricular (RV) volumes in adult populations of acquired RV pressure or volume overload, namely, pulmonary hypertension (PH) and carcinoid heart disease, respectively. Three-dimensional and 2D echocardiographic indices were also compared for identifying RV dysfunction in PH

The nature of fibrous dysplasia

Fibrous dysplasia has been regarded as a developmental skeletal disorder characterized by replacement of normal bone with benign cellular fibrous connective tissue. It has now become evident that fibrous dysplasia is a genetic disease caused by somatic activating mutation of the Gsα subunit of G protein-coupled receptor resulting in upregulation of cAMP. This leads to defects in differentiation of osteoblasts with subsequent production of abnormal bone in an abundant fibrous stroma. In addition there is an increased production of IL-6 by mutated stromal fibrous dysplastic cells that induce osteoclastic bone resorption

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Discriminative and predictive properties of disease-specific and generic health status indexes in elderly COPD patients

<p>Abstract</p> <p>Background</p> <p>The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD) is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA) have comparable prognostic value.</p> <p>Methods</p> <p>We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA) study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1). We classified patients' health status using tertiles of the Saint George Respiratory Questionnaire (SGRQ) and a MDA including functional (the 6' walking test, WT), cognitive (Mini-Mental State Examination, MMSE) and affective status (Geriatric Depression Scale, GDS). The agreement of the classification methods was calculated using the kappa statistic, and survival associated with group membership was evaluated using survival analysis.</p> <p>Results</p> <p>Pulmonary function, expressed by the FEV1, worsened with increasing SGRQ or MDA scores. Cognitive function was not associated with the SGRQ, while physical performance and mood status were impaired only in the highest tertile of SGRQ. A poor agreement was found between the two classification systems tested (k = 0.194). Compared to people in the first tertile of SGRQ score, those in the second tertile had a sex-adjusted HR of 1.22 (0.75 – 1.98) and those in the third tertile of 2.90 (1.92 – 4.40). The corresponding figures of the MDA were 1.49 (95% CI 1.02 – 2.18) and 2.01 (95% CI: 1.31 – 3.08). After adjustment for severity of obstruction, only a SGRQ in the upper tertile was associated with mortality (HR: 1.86; 95% CI: 1.14 – 3.02).</p> <p>Conclusion</p> <p>In elderly outpatients with mild-moderate COPD, a disease-specific health status index seems to be a better predictor of death compared to a MDA.</p

Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling

Although ErbB receptors have been implicated in the progression of prostate cancer, little is known about proteins that may mediate their interactions with the androgen receptor (AR). Ebp1, a protein cloned via its association with the ErbB3 receptor, binds the AR and inhibits androgen-regulated transactivation of wild-type AR in COS cells. As the complement of coregulators in different cells are important for AR activity, we determined the effect of Ebp1 on AR function in prostate cancer cell lines. In addition, we examined the regulation of Ebp1 function by the ErbB3/4 ligand heregulin (HRG). In this study, we demonstrate, using several natural AR-regulated promoters, that Ebp1 repressed transcriptional activation of wild-type AR in prostate cancer cell lines. Downregulation of Ebp1 expression in LNCaP cells using siRNA resulted in activation of AR in the absence of androgen. Ebp1 associated with ErbB3 in LNCaP cells in the absence of HRG, but HRG induced the dissociation of Ebp1 from ErbB3. In contrast, HRG treatment enhanced both the association of Ebp1 with AR and also the ability of Ebp1 to repress AR transactivation. These studies suggest that Ebp1 is an AR corepressor whose biological activity can be regulated by the ErbB3 ligand, HRG

The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7.

Castration-resistant (CR) prostate cancer (PCa) partly arises due to persistence of androgen receptor (AR) transcriptional activity in the absence of cognate ligand. An emerging mechanism underlying the CRPCa phenotype and predicting response to therapy is the expression of the constitutively-active AR-V7 splice variant generated by AR cryptic exon 3b inclusion. Here, we explore the role of the RNA-binding protein (RBP) Sam68 (encoded by KHDRBS1), which is over-expressed in clinical PCa, on AR-V7 expression and transcription function. Using a minigene reporter, we show that Sam68 controls expression of exon 3b resulting in an increase in endogenous AR-V7 mRNA and protein expression in RNA-binding-dependent manner. We identify a novel protein-protein interaction between Sam68 and AR-V7 mediated by a common domain shared with full-length AR, and observe these proteins in the cell nucleoplasm. Using a luciferase reporter, we demonstrate that Sam68 co-activates ligand-independent AR-V7 transcriptional activity in an RNA-binding-independent manner, and controls expression of the endogenous AR-V7-specific gene target UBE2C. Our data suggest that Sam68 has separable effects on the regulation of AR-V7 expression and transcriptional activity, through its RNA-binding capacity. Sam68 and other RBPs may control expression of AR-V7 and other splice variants as well as their downstream functions in CRPCa

An enhanced partial order curve comparison algorithm and its application to analyzing protein folding trajectories

<p>Abstract</p> <p>Background</p> <p>Understanding how proteins fold is essential to our quest in discovering how life works at the molecular level. Current computation power enables researchers to produce a huge amount of folding simulation data. Hence there is a pressing need to be able to interpret and identify novel folding features from them.</p> <p>Results</p> <p>In this paper, we model each folding trajectory as a multi-dimensional curve. We then develop an effective multiple curve comparison (MCC) algorithm, called the <it>enhanced partial order (EPO) </it>algorithm, to extract features from a set of diverse folding trajectories, including both successful and unsuccessful simulation runs. The EPO algorithm addresses several new challenges presented by comparing high dimensional curves coming from folding trajectories. A detailed case study on miniprotein Trp-cage <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> demonstrates that our algorithm can detect similarities at rather low level, and extract biologically meaningful folding events.</p> <p>Conclusion</p> <p>The EPO algorithm is general and applicable to a wide range of applications. We demonstrate its generality and effectiveness by applying it to aligning multiple protein structures with low similarities. For user's convenience, we provide a web server for the algorithm at <url>http://db.cse.ohio-state.edu/EPO</url>.</p

Backward walking training improves balance in school-aged boys

<p>Abstract</p> <p>Background</p> <p>Falls remain a major cause of childhood morbidity and mortality. It is suggested that backward walking (BW) may offer some benefits especially in balance and motor control ability beyond those experienced through forward walking (FW), and may be a potential intervention for prevention of falls. The objective of this study was to investigate the effects of BW on balance in boys.</p> <p>Methods</p> <p>Sixteen healthy boys (age: 7.19 ± 0.40 y) were randomly assigned to either an experimental or a control group. The experimental group participated in a BW training program (12-week, 2 times weekly, and 25-min each time) but not the control group. Both groups had five dynamic balance assessments with a Biodex Stability System (anterior/posterior, medial/lateral, and overall balance index) before, during and after the training (week- 0, 4, 8, 12, 24). Six control and six experimental boys participated in a study comparing kinematics of lower limbs between FW and BW after the training (week-12).</p> <p>Results</p> <p>The balance of experimental group was better than that of control group after 8 weeks of training (<it>P </it>< 0.01), and was still better than that of control group (<it>P </it>< 0.05), when the BW training program had finished for 12 weeks. The kinematic analysis indicated that there was no difference between control and experimental groups in the kinematics of both FW and BW gaits after the BW training (<it>P </it>> 0.05). Compared to FW, the duration of stance phase of BW tended to be longer, while the swing phase, stride length, walking speed, and moving ranges of the thigh, calf and foot of BW decreased (<it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Backward walking training in school-aged boys can improve balance.</p