KRAS mutations by digital PCR in circulating tumor cells isolated from the mesenteric vein are associated with residual disease and overall survival in resected colorectal cancer patients.

PURPOSE: In colorectal cancer (CRC), circulating tumor cells (CTCs) are released into the mesenteric veins (MV). We chose to determine whether KRAS mutations detected in CTCs from blood obtained at the time of surgery could be a marker of survival. METHODS: From 52 surgically resected CRC patients who later relapsed, samples of tumor tissue, normal tissue, and blood from the peripheral vein (PV) and MV were obtained from each patient at the time of surgery. KRAS mutations were assessed by Sanger sequencing and digital PCR (DGPCR) in tissue samples and by DGPCR in CTCs. Mutant KRAS copy number was assessed in CTCs. Results were correlated with overall survival (OS). RESULTS: Sanger sequencing detected KRAS mutations in ten tumor samples (19.2%), while DGPCR detected mutations in 30 (58%). Mutations were detected in CTCs in 21 MV samples (40.4%) and 18 PV samples (34.6%). Patients with G13D mutations in CTCs from the MV had shorter OS than those with G12D mutations (28.1 vs 54.6 months; p = 0.025). Patients with a high mutant KRAS copy number in CTCs had shorter OS than those with a low mutant KRAS copy number (MV: 20.5 vs 43.7 months; p = 0.002; PV: 15.1 vs 38.2 months; p = 0.027). CONCLUSION: DGPCR is more efficient than Sanger sequencing for detecting KRAS mutations. KRAS G13D mutations and high mutant KRAS copy number are associated with shorter OS. The analysis of KRAS mutations in CTCs from blood obtained at the time of surgery can identify patients with a higher risk of relapse.

Prognostic Impact of miR-200 Family Members in Plasma and Exosomes from Tumor-Draining versus Peripheral Veins of Colon Cancer Patients.

OBJECTIVE: To evaluate the prognostic potential of expression levels of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429, miR-141) in plasma and exosomes from the tumor-draining vein (mesenteric vein [MV]) and peripheral vein (PV) of colon cancer (CC) patients. METHODS: We analyzed the expression of miR-200 family members in matched samples of MV and PV plasma from 50 resected patients with CC and correlated our findings with overall survival (OS). We also examined the content of these microRNAs in MV and PV exosomes. RESULTS: Expression levels were higher in MV than in PV (miR-200a, p < 0.001; miR-200b, p < 0.001; miR-429, p = 0.01; miR-200c, p = 0.05; miR-141, p = 0.05). Low levels of both miR-200c and miR-141 in MV plasma were associated with longer OS (p = 0.02). This association was maintained for the MV exosome cargo of miR-200c and miR-141 (p = 0.02). CONCLUSION: Our findings provide the first indication that expression levels of miR-200c and miR-141 in MV plasma can identify CC patients with poor prognosis. In addition, our results lend further support to the premise that tumor-draining veins constitute a better source of biomarkers than do PVs.

[Case management as a methodology for connecting the health and social care systems in Spain]. / La gestión de casos como metodología para la conexión de los sistemas sanitario y social en España.

OBJECTIVE: The aim of this paper is to present the assessment of a case management project, implemented with chronic patients in Valencia, for the integration of health and social care. This project is linked with the 'Sustainable Socio-Health Model'. LOCATION: Health department 06 in Valencia. PARTICIPANTS: The target groups were chronic patients of 65 years and over. INTERVENTIONS: A non-randomized non-blinded comparative study with an intervention and control group. The intervention consisted in the creation of an interdisciplinary case management team, the use of a common portfolio of resources, and its application to a pilot sample with an intervention period of 6-9 months. MAIN MEASUREMENTS: Diseases (ICD-9), functional capacity, use of health and social resources, satisfaction, unit cost services. RESULTS: There was an increase in the combined use of health and social resources in the intervention group, which included social day centers (21.8% in the intervention group compared to 9.8% in the control group), in coordination with primary care (suggested as the only health resource in 55.4% of cases). There was a decrease in the number of medical visits in the intervention group (43.6% versus 74.5% in the control group). Increased patient satisfaction (55.5% in the intervention group compared to 29.4% in the control group) was observed. At least an extra 4.4% of patients were treated using hospital resources without increasing costs. CONCLUSIONS: Case management using a common unique portfolio of health and social resources can improve the coordination of resources, increases patient satisfaction and increases the capacity of using of hospital resources.

[Application of the Community Assessment Risk Screen in Primary Care centres of the Valencia Health System]. / Aplicación de The Community Assessment Risk Screen en centros de atención primaria del Sistema Sanitario Valenciano.

OBJECTIVE: Application of The Community Assessment Risk Screen (CARS) tool for detection of chronic elderly patients at risk of hospital readmission and the viability study for its inclusion in health information systems. DESIGN: Retrospective cohort study. LOCATION: Health Departments 6, 10, and 11 from the Valencia Community. PARTICIPANTS: Patients of 65 and over seen in 6 Primary Care centres in December 2008. The sample consisted of 500 patients (sampling error=±4.37%, sampling fraction=1/307). VARIABLES: The CARS tools includes 3items: Diagnostics (heart diseases, diabetes, myocardial infarction, stroke, COPD, cancer), number of prescribed drugs and hospital admissions or emergency room visits in the previous 6months. The data came from SIA-Abucasis, GAIA and MDS, and were compared by Primary Care professionals. The end-point was hospital admission in 2009. RESULTS: CARS risk levels are related to future readmission (P<.001). The value of sensitivity and specificity is 0.64; the tool accurately identifies patients with low probability of being hospitalized in the future (negative predictive value=0.91, diagnostic efficacy=0.67), but has a positive predictive value of 0.24. CONCLUSIONS: CARS does not properly identify the population at high risk of hospital readmission. However, if it could be revised and the positive predictive value improved, it could be incorporated into the Primary Care computer systems and be useful in the initial screening and grouping of chronic patients at risk of hospital readmission.

LincRNA-p21 Levels Relates to Survival and Post-Operative Radiotherapy Benefit in Rectal Cancer Patients.

LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. In the present study, we aimed to analyze the clinical value of lincRNA-p21 in 177 resected stage I-III colorectal cancer (CRC) patients. Tumor and normal paired tissue and plasma samples from tumor-draining mesenteric veins and paired peripheral veins were analyzed. LincRNA-p21 expression was determined by RTqPCR and correlated with disease-free (DFS) and overall survival (OS). LincRNA-p21 was downregulated in tumor versus normal tissue (p = 0.0012). CRC patients with high lincRNA-p21 expression had shorter DFS (p = 0.0372) and shorter OS (p = 0.0465). Of note, the major prognostic impact was observed in the subset of rectal cancer patients where patients with high lincRNA-p21 levels had worse DFS (p = 0.0226) and OS (p = 0.0457). Interestingly, rectal cancer patients with high lincRNA-p21 benefited from post-operative chemoradiotherapy, as indicated by a longer OS in the group of high lincRNA-p21 patients receiving post-operative chemoradiotherapy (p = 0.04). Finally, patients with high lincRNA-p21 levels in mesenteric vein (MV) had shorter OS (p = 0.0329). LincRNA-p21 is a marker of advanced disease and worse outcome in CRC. Moreover, rectal cancer patients with high lincRNA-p21 levels could benefit from post-operative chemoradiotherapy, and plasmatic-lincRNA-p21 is a promising liquid biopsy biomarker.

Nurses' and physicians' knowledge and skills in non-invasive ventilation: Equipment and contextual influences. / Conocimiento y habilidades de enfermeras y médicos en ventilación mecánica no invasiva: equipamiento e influencias contextuales.

OBJECTIVES: To assess non-invasive ventilation knowledge and skills among nurses and physicians in different contexts: equipment and contextual influences. METHOD: Cross-sectional, descriptive study in 4 intensive care units (ICU) (1 surgical, 3 medical-surgical), 1 postsurgical recovery unit, 2 emergency departments (ED) and 3 wards, in 4 hospitals (3 university, 1 community) with 407 professionals. A 13-item survey, validated in the setting, was applied (Kappa index, 0.97 (95% CI [.965-.975]). RESULTS: Nurses (63.7% response); physicians (39% response). The overall percentage of correct responses was 50%. Scored from 1 to 5, with lower scores reflecting more knowledge, nurses scored 3.27±.5 vs 2.62±.5 physicians, respectively (mean difference,.65 (95% CI: .48-.82, P<.001). There were no differences between hospitals or units (P=.07 and P=.09). A notable percentage of respondents incorrectly identified the patient-ventilator synchronization strategy as "covering the expiratory port" (intentional leaks) and pressing the mask against the patient's face (unintentional leaks) (28.2% ICU, 22.5% ED, 8.3% postoperative resuscitation, 61.5% wards), with no difference between nurses and physicians (27.9% vs 23.4%, P=.6). Only 50% of nurse respondents correctly answered a question about measuring mask size and just 11.7% of the nurses knew the "2-finger fit" adjustment. CONCLUSIONS: There was no difference in nurses' and physicians' knowledge according to the setting studied. The lack of knowledge regarding NIV therapy depended on training received and material available. To reduce the existent confusion between intentional and nonintentional leak, the use of a single type of NIV supply and providing an appropriate level of training for nurses is recommended.

Two Doses of oxaliplatin with capecitabine (XELOX) in metastatic colorectal cancer.

PURPOSE: Phase II/III studies have shown XELOX to be as effective as FOLFOX in patients with advanced colorectal cancer (CRC). The study was designed to evaluate the activity and tolerability of XELOX in CRC. In August 2002, we began a prospective study of XELOX as first-line therapy for patients with metastatic CRC. Twenty-two patients were enrolled between November 2002 and August 2003 (series I). An interim analysis performed in August 2003 revealed that 32% of patients required a dose reduction of oxaliplatin because of toxicity. From August 2003 to April 2005, an additional 20 patients were included (series II). This second group of patients received oxaliplatin at a lower dose. PATIENTS AND METHODS: The first 22 patients (series I) included received oxaliplatin 130 mg/m(2) on day 1 plus capecitabine 2000 mg/m(2) daily on days 1-15 (3-week cycle). The second set of 20 patients (series II) received oxaliplatin 85 mg/m(2) on day 1; the dose of capecitabine and the frequency of administration were not modified. RESULTS: Patient characteristics were well balanced in the 2 series. Overall response (series I vs. II): 41% vs. 65%; median time to progression was similar: 10.51 vs. 10.92 (log-rank test, P = .79). Median survival was similar in the 2 series: 19.55 vs. 21.18 months (log-rank test, P = .61). Grade 3/4 toxicity (series I vs. II): peripheral neuropathy, 14% vs. 0 (P = .23). CONCLUSION: In patients with advanced CRC, in combination with capecitabine, oxaliplatin 85 mg/m(2) is as effective with lower toxicity when compared with oxaliplatin 130 mg/m(2).

Suitability of the health and social care resources for persons requiring long-term care in Spain: an empirical approach.

The objective of this paper is to examine the suitability of specific facilities for dependent persons for meeting users' needs. A total of 1265 users of social and health facilities for dependent persons were interviewed in a study carried out in a typical southern European region with a Mediterranean welfare system: the Valencia Autonomous Region in Spain. Data were obtained on users' socio-demographic profile, health, functional dependence, cognition, social support and housing suitability. Based on these data and the institutional definitions of the specific facilities for dependent persons, the suitability index was drawn up for each facility and suitability was evaluated using discriminant analysis. The results give a high suitability index for most of the facilities (between 0.661 for Units for Home Hospitalisation and 1.000 for Units for Psychiatric Hospitalisation). But a significant percentage of patients (17% in Hospitals for Chronically Ill and Long-stay Patients) could be cared for in different facilities to the ones they actually use.

Impact of a primary-based telemonitoring programme in HRQOL, satisfaction and usefulness in a sample of older adults with chronic diseases in Valencia (Spain).

BACKGROUND: Chronic patients are frequent users of healthcare services and are prone to hospital admissions. In Valencia (Spain) the Valcronic programme aims to manage chronic patients through different levels of telemonitoring and telecare. This paper examines the impact of the Valcronic programme on self-perceived HRQOL in a one-year period and on perceptions of satisfaction and usefulness in a sample of older adults with chronic diseases. METHODS: The sample (n=74) was randomly selected from Valcronic users and was stratified considering different variables. HRQOL was assessed using the EQ-5D questionnaire at two points in time: before the beginning of the Valcronic programme and after a one-year follow-up. Satisfaction and usefulness were evaluated one year after users' inclusion. RESULTS: The whole sample experienced improvement, although not significant, of its HRQOL; patients over 75 showed impairment. Patients with at least one problem in the EQ-5D dimensions decreased after one year (82.43% vs. 74.32%). Users' perceptions of satisfaction and usefulness were highly positive. CONCLUSIONS: Our sample benefited from the Valcronic programme, experiencing an improvement in their HRQOL, a decreased use of health resources or high satisfaction levels. IMPLICATIONS: Further adjustments are needed to address a comprehensive response to the needs of the global population of reference.

Identifying High-Risk Stage II Colon Cancer Patients: A Three-MicroRNA-Based Score as a Prognostic Biomarker.

BACKGROUND: The potential benefit of adjuvant chemotherapy in surgically resected patients with stage II colorectal cancer is controversial. The current guidelines, which are based solely on clinical factors, have limited usefulness, and a clear need exists for biomarkers to supplement the clinical information. MicroRNAs (miRNAs) have previously been shown to be useful cancer biomarkers. In the present study, we assessed the usefulness of a miRNA score to help identify the subset of high-risk patients likely to benefit from adjuvant chemotherapy. PATIENTS AND METHODS: Six miRNAs previously identified as prognostic markers in Asian patients (miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215) were studied in tumor samples from 71 white patients with stage II colon cancer. RESULTS: Three miRNAs (miR-103a-3p, miR-143-5p, and miR-215) emerged as independent prognostic markers on multivariate analysis and were used to construct a miRNA-based score that classified patients into high- and low-risk groups. The patients in the high-risk group had significantly shorter disease-free survival compared with their low-risk counterparts (P = .003). The time-dependent receiver operating characteristic curve analysis showed that our 3-miRNA score improved the prediction of outcome when added to the clinical features (P = .023). CONCLUSION: Our 3-miRNA score added valuable prognostic information to the clinical features in stage II colon cancer. Further research in this field could provide useful tools to determine whether adjuvant chemotherapy would benefit patients with stage II colon cancer after surgery.

Differential MIR-21 expression in plasma from mesenteric versus peripheral veins: an observational study of disease-free survival in surgically resected colon cancer patients.

Findings on the role of plasma miR-21 expression in colorectal cancer are contradictory. Before reaching a peripheral vein (PV), microRNAs released by the tumor are dispersed throughout the body. We hypothesized that blood drawn from the mesenteric vein (MV) near the site of the primary tumor could provide more homogeneous information than blood drawn from the PV.We have analyzed miR-21 expression in matched samples of tumor tissue, normal tissue, MV plasma, and PV plasma in 57 surgically resected patients with colon cancer and correlated our findings with clinical characteristics and disease-free survival (DFS).miR-21 expression was higher in MV than PV plasma (P = 0.014) and in tumor than in normal tissue (P < 0.001). Patients with high levels of miR-21 in MV plasma had shorter DFS (P = 0.05) than those with low levels, and those with high levels in both MV and PV plasma had shorter DFS than all other patients (P = 0.01).Our findings suggest that the primary tumor in colon cancer releases high concentrations of miR-21 in the MV but that these concentrations are later diluted in the circulatory system. MV expression of miR-21 may be a stronger prognostic marker than PV expression.

Towards a new welfare state: the social sustainability principle and health care strategies.

In this paper we propose a social and health care model that offers alternatives to three problems arising in converging European welfare states, particularly in the southern nations: the rise in demand for services and features linked to the ageing process, the increase in dependency and the crisis of informal support. Development of the principles of social sustainability implies re-formulation of the regulatory, care, economic, administrative, cultural, and axiological framework enabling a response to the needs of long term care without compromising the welfare of future generations. Together with this principle, quality of life elevated to a subjective right directs attention towards the sphere closest to citizens, eliminating all barriers, which hamper exercise of this right. All of the above produces economic and social costs which must be accepted from a viewpoint of social co-responsibility, which brings with it the supply of welfare individually, without detriment to the exercise of state responsibility in guaranteeing a social protection system of a universal nature.

Iterative reconstruction of CT images on GPUs.

Although widely used in nuclear medicine (gamma-camera, single photon emission computed tomography (SPECT), positron emission tomography (PET)), iterative reconstruction has not yet penetrated in CT. The main reason for this is that data sets in CT are much larger than in nuclear medicine and iterative reconstruction then becomes computationally very intensive. Graphical Processing Units (GPUs) provide the possibility to reduce effectively the high computational cost of their implementation. It is the goal of this work to develop a GPU-based algorithm to reconstruct high quality images from under sampled and noisy projection data.

Estimated radiation dose reduction using non-linear diffusion method in computed radiography.

In this paper we use a non-linear diffusion method to filter the inherent noise in a Computed Radiography (CR) for reducing the dose absorbed by the patients especially children in pediatric applications, related with the exposure mAs. The method is implemented in order to create a lower CR dose based on the selection of lower X-ray exposure and with a reduction of the noise using a non-linear diffusion method. The impact of several milliAmpere-seconds (mAs) setting on image quality has been studied using the RANDO phantom. The obtained results show good agreements between the filtered images and real images in terms of noise variance measurements. The new CR images allow medical researchers to analyze how a low dose affects the patient diagnosis.

Fast parallel algorithm for CT image reconstruction.

In X-ray computed tomography (CT) the X rays are used to obtain the projection data needed to generate an image of the inside of an object. The image can be generated with different techniques. Iterative methods are more suitable for the reconstruction of images with high contrast and precision in noisy conditions and from a small number of projections. Their use may be important in portable scanners for their functionality in emergency situations. However, in practice, these methods are not widely used due to the high computational cost of their implementation. In this work we analyze iterative parallel image reconstruction with the Portable Extensive Toolkit for Scientific computation (PETSc).

Medical image restoration with different types of noise.

The images obtained by X-Ray or computed tomography (CT) in adverse conditions may be contaminated with noise that can affect the detection of diseases. A large number of image processing techniques (filters) have been proposed to remove noise. These techniques depend on the type of noise present in the image. In this work, we propose a method designed to reduce the Gaussian, the impulsive and speckle noise and combined noise. This filter, called PGNDF, combines a non-linear diffusive filter with a peer group with fuzzy metric technique. The proposed filter is able to reduce efficiently the image noise without any information about what kind of noise might be present. To evaluate the filter performance, we use mammographic images from the mini- MIAS database which we have damaged by adding Gaussian, impulsive and speckle noises of different magnitudes. As a result, the proposed method obtains a good performance in most of the different types of noise.

A review of programs to alleviate the burden of informal caregivers of dependent persons.

The review of interventions currently available to alleviate the burden of informal caregivers of dependent persons has both social and political relevance considering the increasing number of elderly dependent persons. Respite services and programs for psycho-social intervention are the main methods of dealing with this burden. Study of the main research carried out to date on such interventions enables us to organize more efficient services, especially considering the enactment of the Law on Dependence in Spain in January 2007 and the need for other European and international governments to establish systems to meet the needs of the growing dependent population.

The care of the informal caregiver's burden by the Spanish public system of social welfare: a review.

This work analyzes the public social services system developed in Spain to attend dependent persons and their informal caregivers, examining in a more detailed way the current capacity of the Spanish public In-Home Help Service (HHS) to meet the demands of dependent elderly persons and its impact on their informal caregiver's burden. We begin with a brief introduction of the services by the Spanish public social services system developed to attend dependency; next, the evolution of the Spanish public HHS is described in a thorough way to identify the pros and cons of this service regarding the informal caregivers' burden of dependent elders. Finally, recommendations are proposed to redesign and restructure this public in-home service to lessen the informal caregiver's burden.