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Sample records for accurately identify patients

  1. Enhanced Liver Fibrosis (ELF) test accurately identifies liver fibrosis in patients with chronic hepatitis C.

    PubMed

    Parkes, J; Guha, I N; Roderick, P; Harris, S; Cross, R; Manos, M M; Irving, W; Zaitoun, A; Wheatley, M; Ryder, S; Rosenberg, W

    2011-01-01

    Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy.

  2. Using an Educational Electronic Documentation System to Help Nursing Students Accurately Identify Nursing Diagnoses

    ERIC Educational Resources Information Center

    Pobocik, Tamara J.

    2013-01-01

    The use of technology and electronic medical records in healthcare has exponentially increased. This quantitative research project used a pretest/posttest design, and reviewed how an educational electronic documentation system helped nursing students to identify the accurate related to statement of the nursing diagnosis for the patient in the case…

  3. SNP-microarrays can accurately identify the presence of an individual in complex forensic DNA mixtures.

    PubMed

    Voskoboinik, Lev; Ayers, Sheri B; LeFebvre, Aaron K; Darvasi, Ariel

    2015-05-01

    Common forensic and mass disaster scenarios present DNA evidence that comprises a mixture of several contributors. Identifying the presence of an individual in such mixtures has proven difficult. In the current study, we evaluate the practical usefulness of currently available "off-the-shelf" SNP microarrays for such purposes. We found that a set of 3000 SNPs specifically selected for this purpose can accurately identify the presence of an individual in complex DNA mixtures of various compositions. For example, individuals contributing as little as 5% to a complex DNA mixture can be robustly identified even if the starting DNA amount was as little as 5.0ng and had undergone whole-genome amplification (WGA) prior to SNP analysis. The work presented in this study represents proof-of-principle that our previously proposed approach, can work with real "forensic-type" samples. Furthermore, in the absence of a low-density focused forensic SNP microarray, the use of standard, currently available high-density SNP microarrays can be similarly used and even increase statistical power due to the larger amount of available information.

  4. A Maximum NEC Criterion for Compton Collimation to Accurately Identify True Coincidences in PET

    PubMed Central

    Chinn, Garry; Levin, Craig S.

    2013-01-01

    In this work, we propose a new method to increase the accuracy of identifying true coincidence events for positron emission tomography (PET). This approach requires 3-D detectors with the ability to position each photon interaction in multi-interaction photon events. When multiple interactions occur in the detector, the incident direction of the photon can be estimated using the Compton scatter kinematics (Compton Collimation). If the difference between the estimated incident direction of the photon relative to a second, coincident photon lies within a certain angular range around colinearity, the line of response between the two photons is identified as a true coincidence and used for image reconstruction. We present an algorithm for choosing the incident photon direction window threshold that maximizes the noise equivalent counts of the PET system. For simulated data, the direction window removed 56%–67% of random coincidences while retaining > 94% of true coincidences from image reconstruction as well as accurately extracted 70% of true coincidences from multiple coincidences. PMID:21317079

  5. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    SciTech Connect

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  6. Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?

    PubMed Central

    Visser, P; Scheltens, P; Verhey, F

    2005-01-01

    Background: Drugs effective in Alzheimer-type dementia have been tested in subjects with mild cognitive impairment (MCI) because these are supposed to have Alzheimer's disease in the predementia stage. Objectives: To investigate whether MCI criteria used in these drug trials can accurately diagnose subjects with predementia Alzheimer's disease. Methods: MCI criteria of the Gal-Int 11 study, InDDEx study, ADCS memory impairment study, ampakine CX 516 study, piracetam study, and Merck rofecoxib study were applied retrospectively in a cohort of 150 non-demented subjects from a memory clinic. Forty two had progressed to Alzheimer type dementia during a five year follow up period and were considered to have predementia Alzheimer's disease at baseline. Outcome measures were the odds ratio, sensitivity, specificity, and positive and negative predictive value. Results: The odds ratio of the MCI criteria for predementia Alzheimer's disease varied between 0.84 and 11. Sensitivity varied between 0.46 and 0.83 and positive predictive value between 0.43 and 0.76. None of the criteria combined a high sensitivity with a high positive predictive value. Exclusion criteria for depression led to an increase in positive predictive value and specificity at the cost of sensitivity. In subjects older than 65 years the positive predictive value was higher than in younger subjects. Conclusions: The diagnostic accuracy of MCI criteria used in trials for predementia Alzheimer's disease is low to moderate. Their use may lead to inclusion of many patients who do not have predementia Alzheimer's disease or to exclusion of many who do. Subjects with moderately severe depression should not be excluded from trials in order not to reduce the sensitivity. PMID:16170074

  7. Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes

    PubMed Central

    Martei, Yehoda M; Matro, Jennifer M

    2015-01-01

    Identifying patients at high risk of breast cancer recurrence has important implications not only for enabling the ability to provide accurate information to patients but also the potential to improve patient outcomes. Patients at high recurrence risk can be offered appropriate treatment to improve the overall survival. However, the major challenge is identifying patients with early-stage breast cancer at lower risk who may be spared potentially toxic therapy. The successful integration of molecular assays into clinical practice may address the problem of overtreatment and improve overall patient outcomes. PMID:26504408

  8. PoopMD, a Mobile Health Application, Accurately Identifies Infant Acholic Stools.

    PubMed

    Franciscovich, Amy; Vaidya, Dhananjay; Doyle, Joe; Bolinger, Josh; Capdevila, Montserrat; Rice, Marcus; Hancock, Leslie; Mahr, Tanya; Mogul, Douglas B

    2015-01-01

    Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease in the United States. Education of parents in the perinatal period with stool cards depicting acholic and normal stools has been associated with improved time-to-diagnosis and survival in BA. PoopMD is a mobile application that utilizes a smartphone's camera and color recognition software to analyze an infant's stool and determine if additional follow-up is indicated. PoopMD was developed using custom HTML5/CSS3 and wrapped to work on iOS and Android platforms. In order to define the gold standard regarding stool color, seven pediatricians were asked to review 45 photographs of infant stool and rate them as acholic, normal, or indeterminate. Samples for which 6+ pediatricians demonstrated agreement defined the gold standard, and only these samples were included in the analysis. Accuracy of PoopMD was assessed using an iPhone 5s with incandescent lighting. Variability in analysis of stool photographs as acholic versus normal with intermediate rating weighted as 50% agreement (kappa) was compared between three laypeople and one expert user. Variability in output was also assessed between an iPhone 5s and a Samsung Galaxy S4, as well as between incandescent lighting and compact fluorescent lighting. Six-plus pediatricians agreed on 27 normal and 7 acholic photographs; no photographs were defined as indeterminate. The sensitivity was 7/7 (100%). The specificity was 24/27 (89%) with 3/27 labeled as indeterminate; no photos of normal stool were labeled as acholic. The Laplace-smoothed positive likelihood ratio was 6.44 (95% CI 2.52 to 16.48) and the negative likelihood ratio was 0.13 (95% CI 0.02 to 0.83). kappauser was 0.68, kappaphone was 0.88, and kappalight was 0.81. Therefore, in this pilot study, PoopMD accurately differentiates acholic from normal color with substantial agreement across users, and almost perfect agreement across two popular smartphones and ambient light settings. Poop

  9. Identifying Accurate Equivalents between Turkish and Arabic for Foreign Language Teaching

    ERIC Educational Resources Information Center

    Kadizade, Esma Dumanli

    2015-01-01

    The aim of this study is to make a list of accurate equivalents between Turkish and Arabic in order to help Arabic-speaking students learn Turkish as a second language, and offer teachers a guide to categorize and teach these lists. Equivalence between the different dialects of Turkish has been studied intensively by linguists. However, a review…

  10. Oxygen-enhanced MRI accurately identifies, quantifies, and maps tumor hypoxia in preclinical cancer models

    PubMed Central

    O’Connor, James PB; Boult, Jessica KR; Jamin, Yann; Babur, Muhammad; Finegan, Katherine G; Williams, Kaye J; Little, Ross A; Jackson, Alan; Parker, Geoff JM; Reynolds, Andrew R; Waterton, John C; Robinson, Simon P

    2015-01-01

    There is a clinical need for non-invasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning and therapy monitoring. Oxygen enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (ΔR1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ΔR1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ΔR1, termed “Oxy-R fraction”) would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here we demonstrate that OE-MRI signals are accurate, precise and sensitive to changes in tumor pO2 in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, Oxy-R fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast-enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia non-invasively and is immediately translatable to the clinic. PMID:26659574

  11. Fluorescent labeling reliably identifies Chlamydia trachomatis in living human endometrial cells and rapidly and accurately quantifies chlamydial inclusion forming units.

    PubMed

    Vicetti Miguel, Rodolfo D; Henschel, Kevin J; Dueñas Lopez, Fiorela C; Quispe Calla, Nirk E; Cherpes, Thomas L

    2015-12-01

    Chlamydia replication requires host lipid acquisition, allowing flow cytometry to identify Chlamydia-infected cells that accumulated fluorescent Golgi-specific lipid. Herein, we describe modifications to currently available methods that allow precise differentiation between uninfected and Chlamydia trachomatis-infected human endometrial cells and rapidly and accurately quantify chlamydial inclusion forming units.

  12. Fluorescent labeling reliably identifies Chlamydia trachomatis in living human endometrial cells and rapidly and accurately quantifies chlamydial inclusion forming units

    PubMed Central

    Vicetti Miguel, Rodolfo D.; Henschel, Kevin J.; Dueñas Lopez, Fiorela C.; Quispe Calla, Nirk E.; Cherpes, Thomas L.

    2016-01-01

    Chlamydia replication requires host lipid acquisition, allowing flow cytometry to identify C. trachomatis-infected cells that accumulated fluorescent Golgi-specific lipid. Herein, we describe modifications to currently available methods that allow precise differentiation between uninfected and C. trachomatis-infected human endometrial cells and rapidly and accurately quantify chlamydial inclusion forming units. PMID:26453947

  13. USING AN ACCURATE MASS, TRIPLE QUADRUPOLE MASS SPECTROMETER AND AN ION CORRELATION PROGRAM TO IDENTIFY COMPOUNDS

    EPA Science Inventory

    Most compounds are not found in mass spectral libraries and must be identified by other means. Often, compound identities can be deduced from the compositions of the ions in their mass spectra and review of the chemical literature. Confirmation is provided by mass spectra and r...

  14. An extended set of yeast-based functional assays accurately identifies human disease mutations

    PubMed Central

    Sun, Song; Yang, Fan; Tan, Guihong; Costanzo, Michael; Oughtred, Rose; Hirschman, Jodi; Theesfeld, Chandra L.; Bansal, Pritpal; Sahni, Nidhi; Yi, Song; Yu, Analyn; Tyagi, Tanya; Tie, Cathy; Hill, David E.; Vidal, Marc; Andrews, Brenda J.; Boone, Charles; Dolinski, Kara; Roth, Frederick P.

    2016-01-01

    We can now routinely identify coding variants within individual human genomes. A pressing challenge is to determine which variants disrupt the function of disease-associated genes. Both experimental and computational methods exist to predict pathogenicity of human genetic variation. However, a systematic performance comparison between them has been lacking. Therefore, we developed and exploited a panel of 26 yeast-based functional complementation assays to measure the impact of 179 variants (101 disease- and 78 non-disease-associated variants) from 22 human disease genes. Using the resulting reference standard, we show that experimental functional assays in a 1-billion-year diverged model organism can identify pathogenic alleles with significantly higher precision and specificity than current computational methods. PMID:26975778

  15. Accurate structure prediction of peptide–MHC complexes for identifying highly immunogenic antigens

    SciTech Connect

    Park, Min-Sun; Park, Sung Yong; Miller, Keith R.; Collins, Edward J.; Lee, Ha Youn

    2013-11-01

    Designing an optimal HIV-1 vaccine faces the challenge of identifying antigens that induce a broad immune capacity. One factor to control the breadth of T cell responses is the surface morphology of a peptide–MHC complex. Here, we present an in silico protocol for predicting peptide–MHC structure. A robust signature of a conformational transition was identified during all-atom molecular dynamics, which results in a model with high accuracy. A large test set was used in constructing our protocol and we went another step further using a blind test with a wild-type peptide and two highly immunogenic mutants, which predicted substantial conformational changes in both mutants. The center residues at position five of the analogs were configured to be accessible to solvent, forming a prominent surface, while the residue of the wild-type peptide was to point laterally toward the side of the binding cleft. We then experimentally determined the structures of the blind test set, using high resolution of X-ray crystallography, which verified predicted conformational changes. Our observation strongly supports a positive association of the surface morphology of a peptide–MHC complex to its immunogenicity. Our study offers the prospect of enhancing immunogenicity of vaccines by identifying MHC binding immunogens.

  16. High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells

    PubMed Central

    Sharma, Prabhat K; Wong, Emily B; Napier, Ruth J; Bishai, William R; Ndung'u, Thumbi; Kasprowicz, Victoria O; Lewinsohn, Deborah A; Lewinsohn, David M; Gold, Marielle C

    2015-01-01

    Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1–2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1–2+ MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8+ T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8+ subsets we demonstrated that high expression of CD26 on CD8+ TRAV1–2+ cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161hi was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161dim. Using cell surface expression of CD8, TRAV1–2, and CD26hi in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis. PMID:25752900

  17. High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells.

    PubMed

    Sharma, Prabhat K; Wong, Emily B; Napier, Ruth J; Bishai, William R; Ndung'u, Thumbi; Kasprowicz, Victoria O; Lewinsohn, Deborah A; Lewinsohn, David M; Gold, Marielle C

    2015-07-01

    Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)  TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim) . Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis.

  18. How accurate are we in sending patients to angiography?

    PubMed

    Neves, Marta; Ponce, Pedro; Maia, Pedro; Neves, Fernando

    2014-01-01

    Physical examination (PE), and surveillance and monitoring techniques should be a core part of standard care provided to hemodialysis patients. This study aimed to define which referral criteria within a vascular access (VA) program were associated with indication for therapeutic endovascular intervention (EI). Retrospective study at two vascular centers, considering 1265 procedures between 1 November 2012 and 30 November 2013. All 617 arteriovenous fistulas (AVFs) and 648 arteriovenous grafts (AVGs) referred for angiography were enrolled. Each population was divided into two groups regarding absence (group 1) or presence (group 2) of a significant lesion on the angiogram, contemplating formal indication for EI. On multivariate analysis, factors independently associated with presence of a significant lesion in AVFs were referral due to increased dynamic venous pressure (p = 0.01), suspected stenosis by abnormal PE (p = 0.019), confirmed reduction in access flow rate (p = 0.003), and mean Kt/V < 1.4 (p = 0.004). In AVGs, although multivariate analysis did not find independent association of studied factors with presence of significant stenoses, 97.2% of the exams revealed relevant lesions previously suspected clinically. Aside from surveillance strategies, monitoring strategies including routine PE of the VA are imperative as an integral part of evaluation, especially in AVFs.

  19. Preoperative patient assessment: Identifying patients at high risk.

    PubMed

    Boehm, O; Baumgarten, G; Hoeft, A

    2016-06-01

    Postoperative mortality remains alarmingly high with a mortality rate ranging between 0.4% and 4%. A small subgroup of multimorbid and/or elderly patients undergoing different surgical procedures naturally confers the highest risk of complications and perioperative death. Therefore, preoperative assessment should identify these high-risk patients and stratify them to individualized monitoring and treatment throughout all phases of perioperative care. A "tailored" perioperative approach might help further reduce perioperative morbidity and mortality. This article aims to elucidate individual morbidity-specific risks. It further suggests approaches to detect patients at the risk of perioperative complications.

  20. Accurate setup of paraspinal patients using a noninvasive patient immobilization cradle and portal imaging

    SciTech Connect

    Lovelock, D. Michael; Hua Chiaho; Wang Ping; Hunt, Margie; Fournier-Bidoz, Nathalie; Yenice, Kamil; Toner, Sean; Lutz, Wendell; Amols, Howard; Bilsky, Mark; Fuks, Zvi; Yamada, Yoshiya

    2005-08-15

    Because of the proximity of the spinal cord, effective radiotherapy of paraspinal tumors to high doses requires highly conformal dose distributions, accurate patient setup, setup verification, and patient immobilization. An immobilization cradle has been designed to facilitate the rapid setup and radiation treatment of patients with paraspinal disease. For all treatments, patients were set up to within 2.5 mm of the design using an amorphous silicon portal imager. Setup reproducibility of the target using the cradle and associated clinical procedures was assessed by measuring the setup error prior to any correction. From 350 anterior/posterior images, and 303 lateral images, the standard deviations, as determined by the imaging procedure, were 1.3 m, 1.6 m, and 2.1 in the ant/post, right/left, and superior/inferior directions. Immobilization was assessed by measuring patient shifts between localization images taken before and after treatment. From 67 ant/post image pairs and 49 lateral image pairs, the standard deviations were found to be less than 1 mm in all directions. Careful patient positioning and immobilization has enabled us to develop a successful clinical program of high dose, conformal radiotherapy of paraspinal disease using a conventional Linac equipped with dynamic multileaf collimation and an amorphous silicon portal imager.

  1. Photometric brown-dwarf classification. I. A method to identify and accurately classify large samples of brown dwarfs without spectroscopy

    NASA Astrophysics Data System (ADS)

    Skrzypek, N.; Warren, S. J.; Faherty, J. K.; Mortlock, D. J.; Burgasser, A. J.; Hewett, P. C.

    2015-02-01

    Aims: We present a method, named photo-type, to identify and accurately classify L and T dwarfs onto the standard spectral classification system using photometry alone. This enables the creation of large and deep homogeneous samples of these objects efficiently, without the need for spectroscopy. Methods: We created a catalogue of point sources with photometry in 8 bands, ranging from 0.75 to 4.6 μm, selected from an area of 3344 deg2, by combining SDSS, UKIDSS LAS, and WISE data. Sources with 13.0 0.8, were then classified by comparison against template colours of quasars, stars, and brown dwarfs. The L and T templates, spectral types L0 to T8, were created by identifying previously known sources with spectroscopic classifications, and fitting polynomial relations between colour and spectral type. Results: Of the 192 known L and T dwarfs with reliable photometry in the surveyed area and magnitude range, 189 are recovered by our selection and classification method. We have quantified the accuracy of the classification method both externally, with spectroscopy, and internally, by creating synthetic catalogues and accounting for the uncertainties. We find that, brighter than J = 17.5, photo-type classifications are accurate to one spectral sub-type, and are therefore competitive with spectroscopic classifications. The resultant catalogue of 1157 L and T dwarfs will be presented in a companion paper.

  2. Probabilistic techniques for obtaining accurate patient counts in Clinical Data Warehouses.

    PubMed

    Myers, Risa B; Herskovic, Jorge R

    2011-12-01

    Proposal and execution of clinical trials, computation of quality measures and discovery of correlation between medical phenomena are all applications where an accurate count of patients is needed. However, existing sources of this type of patient information, including Clinical Data Warehouses (CDWs) may be incomplete or inaccurate. This research explores applying probabilistic techniques, supported by the MayBMS probabilistic database, to obtain accurate patient counts from a Clinical Data Warehouse containing synthetic patient data. We present a synthetic Clinical Data Warehouse, and populate it with simulated data using a custom patient data generation engine. We then implement, evaluate and compare different techniques for obtaining patients counts. We model billing as a test for the presence of a condition. We compute billing's sensitivity and specificity both by conducting a "Simulated Expert Review" where a representative sample of records are reviewed and labeled by experts, and by obtaining the ground truth for every record. We compute the posterior probability of a patient having a condition through a "Bayesian Chain", using Bayes' Theorem to calculate the probability of a patient having a condition after each visit. The second method is a "one-shot" approach that computes the probability of a patient having a condition based on whether the patient is ever billed for the condition. Our results demonstrate the utility of probabilistic approaches, which improve on the accuracy of raw counts. In particular, the simulated review paired with a single application of Bayes' Theorem produces the best results, with an average error rate of 2.1% compared to 43.7% for the straightforward billing counts. Overall, this research demonstrates that Bayesian probabilistic approaches improve patient counts on simulated patient populations. We believe that total patient counts based on billing data are one of the many possible applications of our Bayesian framework. Use of

  3. TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients

    PubMed Central

    Gunnerson, Kyle J.; Shaw, Andrew D.; Chawla, Lakhmir S.; Bihorac, Azra; Al-Khafaji, Ali; Kashani, Kianoush; Lissauer, Matthew; Shi, Jing; Walker, Michael G.; Kellum, John A.

    2016-01-01

    BACKGROUND Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI. STUDY DESIGN We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2–3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement. RESULTS A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76–0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery). CONCLUSION For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance. LEVEL OF EVIDENCE Prognostic study, level I. PMID:26816218

  4. Accurate Identification of MCI Patients via Enriched White-Matter Connectivity Network

    NASA Astrophysics Data System (ADS)

    Wee, Chong-Yaw; Yap, Pew-Thian; Brownyke, Jeffery N.; Potter, Guy G.; Steffens, David C.; Welsh-Bohmer, Kathleen; Wang, Lihong; Shen, Dinggang

    Mild cognitive impairment (MCI), often a prodromal phase of Alzheimer's disease (AD), is frequently considered to be a good target for early diagnosis and therapeutic interventions of AD. Recent emergence of reliable network characterization techniques have made understanding neurological disorders at a whole brain connectivity level possible. Accordingly, we propose a network-based multivariate classification algorithm, using a collection of measures derived from white-matter (WM) connectivity networks, to accurately identify MCI patients from normal controls. An enriched description of WM connections, utilizing six physiological parameters, i.e., fiber penetration count, fractional anisotropy (FA), mean diffusivity (MD), and principal diffusivities (λ 1, λ 2, λ 3), results in six connectivity networks for each subject to account for the connection topology and the biophysical properties of the connections. Upon parcellating the brain into 90 regions-of-interest (ROIs), the average statistics of each ROI in relation to the remaining ROIs are extracted as features for classification. These features are then sieved to select the most discriminant subset of features for building an MCI classifier via support vector machines (SVMs). Cross-validation results indicate better diagnostic power of the proposed enriched WM connection description than simple description with any single physiological parameter.

  5. Accurate Characterization of Benign and Cancerous Breast Tissues: Aspecific Patient Studies using Piezoresistive Microcantilevers

    PubMed Central

    PANDYA, HARDIK J.; ROY, RAJARSHI; CHEN, WENJIN; CHEKMAREVA, MARINA A.; FORAN, DAVID J.; DESAI, JAYDEV P.

    2014-01-01

    Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316 X 10−3 Ω-cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression. PMID:25128621

  6. Toward optimizing patient-specific IMRT QA techniques in the accurate detection of dosimetrically acceptable and unacceptable patient plans

    SciTech Connect

    McKenzie, Elizabeth M.; Balter, Peter A.; Stingo, Francesco C.; Jones, Jimmy; Followill, David S.; Kry, Stephen F.

    2014-12-15

    was no significant difference in the performance of any device between gamma criteria of 2%/2 mm, 3%/3 mm, and 5%/3 mm. Finally, optimal cutoffs (e.g., percent of pixels passing gamma) were determined for each device and while clinical practice commonly uses a threshold of 90% of pixels passing for most cases, these results showed variability in the optimal cutoff among devices. Conclusions: IMRT QA devices have differences in their ability to accurately detect dosimetrically acceptable and unacceptable plans. Field-by-field analysis with a MapCheck device and use of the MapCheck with a MapPhan phantom while delivering at planned rotational gantry angles resulted in a significantly poorer ability to accurately sort acceptable and unacceptable plans compared with the other techniques examined. Patient-specific IMRT QA techniques in general should be thoroughly evaluated for their ability to correctly differentiate acceptable and unacceptable plans. Additionally, optimal agreement thresholds should be identified and used as common clinical thresholds typically worked very poorly to identify unacceptable plans.

  7. Can patients reliably identify safe, high quality care?

    PubMed Central

    Tevis, Sarah E.; Schmocker, Ryan K.; Kennedy, Gregory D.

    2015-01-01

    The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a publicly reported tool that measures patient satisfaction. As both patients and Centers for Medicare & Medicaid Services (CMS) reimbursement rely on survey results as a metric of quality of care, we reviewed the current literature to determine if patient satisfaction correlates with quality, safety, or patient outcomes. We found varying associations between safety culture, process of care measure compliance, and patient outcomes with patient satisfaction on the HCAHPS survey. Some studies found inverse relationships between quality and safety metrics and patient satisfaction. The measure that most reliably correlated with high patient satisfaction was low readmission rate. Future studies using patient specific data are needed to better identify which factors most influence patient satisfaction and to determine if patient satisfaction is a marker of safer and better quality care. Furthermore, the HCAHPS survey should continue to undergo evaluations to assure it generates predictable results. PMID:26413179

  8. An accurate prognostic staging system for hepatocellular carcinoma patients after curative hepatectomy

    PubMed Central

    TOKUMITSU, YUKIO; TAMESA, TAKAO; MATSUKUMA, SATOSHI; HASHIMOTO, NORIAKI; MAEDA, YOSHINARI; TOKUHISA, YOSHIHIRO; SAKAMOTO, KAZUHIKO; UENO, TOMIO; HAZAMA, SHOICHI; OGIHARA, HIROYUKI; FUJITA, YUSUKE; HAMAMOTO, YOSHIHIKO; OKA, MASAAKI; IIZUKA, NORIO

    2015-01-01

    The aim of this study was to develop an accurate predictive system for prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. We pooled data of clinicopathological features of 234 HCC patients who underwent curative hepatectomy. On the basis of the pooled data, we established a simple predictive staging system (PS score) scored by the mathematical product of tumor number and size, and degree of liver function. We compared the prognostic abilities of the PS score (score 0–3) with those of six well-known clinical staging systems. Then, we found that there were significant differences (P<0.05) in both disease-free survival (DFS) and overall survival (OS) between patients with different PS scores (PS score 0 vs. 1; PS score 1 vs. 2), and there was a significant difference in DFS, but not OS, between patients with PS score 2 and those with PS score 3. Moreover, the PS score had smaller values of the Akaike information criterion for both DFS and OS than any of the six well-known clinical staging systems. These results suggest that the PS score serves as a simple, accurate predictor for the prognosis of HCC patients after hepatectomy. PMID:25524574

  9. Ability of bottle cap color to facilitate accurate glaucoma patient-physician communication regarding medication identity

    PubMed Central

    Dave, Pujan; Villarreal, Guadalupe; Friedman, David S.; Kahook, Malik Y.; Ramulu, Pradeep Y.

    2015-01-01

    Objective To determine the accuracy of patient-physician communication regarding topical ophthalmic medication use based on bottle cap color, particularly amongst individuals who may have acquired color vision deficiency from glaucoma. Design Cross-sectional, clinical study. Participants Patients ≥ 18 years old with primary open-angle, primary angle-closure, pseudoexfoliation, or pigment dispersion glaucoma, bilateral visual acuity of 20/400 or better, and no concurrent conditions that may affect color vision. Methods One hundred patients provided color descriptions of 11 distinct medication bottle caps. Patient-produced color descriptors were then presented to three physicians. Each physician matched each color descriptor to the medication they thought the descriptor was describing. Main Outcome Measures Frequency of patient-physician agreement, occurring when all three physicians accurately matched the patient-produced color descriptor to the correct medication. Multivariate regression models evaluated whether patient-physician agreement decreased with degree of better-eye visual field (VF) damage, color descriptor heterogeneity, and/or color vision deficiency, as determined by Hardy-Rand-Rittler (HRR) score and the Lanthony D15 testing index (D15 CCI). Results Subjects had a mean age of 69 (±11) years, with mean VF mean deviation of −4.7 (±6.0) and −10.9 (±8.4) dB in the better- and worse-seeing eyes, respectively. Patients produced 102 unique color descriptors to describe the colors of the 11 tested bottle caps. Among individual patients, the mean number of medications demonstrating patient-physician agreement was 6.1/11 (55.5%). Agreement was less than 15% for 4 medications (prednisolone acetate [generic], betaxolol HCl [Betoptic], brinzolamide/brimonidine [Simbrinza], and latanoprost [Xalatan]). Lower HRR scores and higher D15 CCI (both indicating worse color vision) were associated with greater VF damage (p<0.001). Extent of color vision deficiency

  10. Identifying and assessing psychosis in deaf psychiatric patients.

    PubMed

    Landsberger, Sarah A; Diaz, David R

    2011-06-01

    This article reviews recent research in the area of psychotic disorders in deaf psychiatric patients. Comparisons of the rates of psychotic disorders in the deaf and hearing populations suggest that psychotic disorders occur equally as often or even somewhat less often in the deaf population as in the hearing population. Consideration is given to the limitations of this small body of research, and recommendations for future research are provided. The contradictory literature on hallucinations in the deaf is also reviewed, and current theory about the manner in which hallucinations are manifested and experienced based on audiological history is presented. The challenges encountered by clinicians in accurately assessing symptoms of thought disorganization in deaf people are reviewed. Specifically, the etiology of deafness, language dysfluency, and the skill and training of American Sign Language interpreters are considered as factors impacting accurate diagnosis. Recommendations from the current literature are also provided.

  11. MRI is more accurate than CT for patient-specific total knee arthroplasty.

    PubMed

    Frye, Benjamin M; Najim, Amjad A; Adams, Joanne B; Berend, Keith R; Lombardi, Adolph V

    2015-12-01

    Previous reports have stated that MRI is less accurate than CT for patient specific guide creation in total knee arthroplasty (TKA). Twenty-three TKAs were performed with CT-based guides and 27 with MRI-based guides. A mechanical axis through the central third of the knee was achieved in 88.9% of MRI-guided TKA versus 69.6% of CT-guided TKA (p=0.07). There were nine component outliers in the CT group (39.1%) and two in the MRI group (7.4%, p=0.00768). The relative risk of having an outlier using a CT-based guide was 5.28 times that of an MRI-based guide. Superior overall alignment and fewer outliers were achieved with the use of MRI compared with CT. MRI is the best imaging modality for surgeons wishing to utilize patient specific guides for TKA.

  12. Detailed behavioral assessment promotes accurate diagnosis in patients with disorders of consciousness

    PubMed Central

    Gilutz, Yael; Lazary, Avraham; Karpin, Hana; Vatine, Jean-Jacques; Misha, Tamar; Fortinsky, Hadassah; Sharon, Haggai

    2015-01-01

    Introduction: Assessing the awareness level in patients with disorders of consciousness (DOC) is made on the basis of exhibited behaviors. However, since motor signs of awareness (i.e., non-reflex motor responses) can be very subtle, differentiating the vegetative from minimally conscious states (which is in itself not clear-cut) is often challenging. Even the careful clinician relying on standardized scales may arrive at a wrong diagnosis. Aim: To report our experience in tackling this problem by using two in-house use assessment procedures developed at Reuth Rehabilitation Hospital, and demonstrate their clinical significance by reviewing two cases. Methods: (1) Reuth DOC Response Assessment (RDOC-RA) –administered in addition to the standardized tools, and emphasizes the importance of assessing a wide range of motor responses. In our experience, in some patients the only evidence for awareness may be a private specific movement that is not assessed by standard assessment tools. (2) Reuth DOC Periodic Intervention Model (RDOC-PIM) – current literature regarding assessment and diagnosis in DOC refers mostly to the acute phase of up to 1 year post injury. However, we have found major changes in responsiveness occurring 1 year or more post-injury in many patients. Therefore, we conduct periodic assessments at predetermined times points to ensure patients are not misdiagnosed or neurological changes overlooked. Results: In the first case the RDOC-RA promoted a more accurate diagnosis than that based on standardized scales alone. The second case shows how the RDOC-PIM allowed us to recognize late recovery and promoted reinstatement of treatment with good results. Conclusion: Adding a detailed periodic assessment of DOC patients to existing scales can yield critical information, promoting better diagnosis, treatment, and clinical outcomes. We discuss the implications of this observation for the future development and validation of assessment tools in DOC patients

  13. Accurate patient dosimetry of kilovoltage cone-beam CT in radiation therapy

    SciTech Connect

    Ding, George X.; Duggan, Dennis M.; Coffey, Charles W.

    2008-03-15

    The increased utilization of x-ray imaging in image-guided radiotherapy has dramatically improved the radiation treatment and the lives of cancer patients. Daily imaging procedures, such as cone-beam computed tomography (CBCT), for patient setup may significantly increase the dose to the patient's normal tissues. This study investigates the dosimetry from a kilovoltage (kV) CBCT for real patient geometries. Monte Carlo simulations were used to study the kV beams from a Varian on-board imager integrated into the Trilogy accelerator. The Monte Carlo calculated results were benchmarked against measurements and good agreement was obtained. The authors developed a novel method to calibrate Monte Carlo simulated beams with measurements using an ionization chamber in which the air-kerma calibration factors are obtained from an Accredited Dosimetry Calibration Laboratory. The authors have introduced a new Monte Carlo calibration factor, f{sub MCcal}, which is determined from the calibration procedure. The accuracy of the new method was validated by experiment. When a Monte Carlo simulated beam has been calibrated, the simulated beam can be used to accurately predict absolute dose distributions in the irradiated media. Using this method the authors calculated dose distributions to patient anatomies from a typical CBCT acquisition for different treatment sites, such as head and neck, lung, and pelvis. Their results have shown that, from a typical head and neck CBCT, doses to soft tissues, such as eye, spinal cord, and brain can be up to 8, 6, and 5 cGy, respectively. The dose to the bone, due to the photoelectric effect, can be as much as 25 cGy, about three times the dose to the soft tissue. The study provides detailed information on the additional doses to the normal tissues of a patient from a typical kV CBCT acquisition. The methodology of the Monte Carlo beam calibration developed and introduced in this study allows the user to calculate both relative and absolute

  14. Cocaine withdrawal symptoms identify "Type B" cocaine-dependent patients.

    PubMed

    Ahmadi, Jamshid; Kampman, Kyle; Dackis, Charles; Sparkman, Thorne; Pettinati, Helen

    2008-01-01

    Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.

  15. Organizing patient safety research to identify risks and hazards

    PubMed Central

    Battles, J; Lilford, R

    2003-01-01

    Patient safety has become an international priority with major research programmes being carried out in the USA, UK, and elsewhere. The challenge is how to organize research efforts that will produce the greatest yield in making health care safer for patients. Patient safety research initiatives can be considered in three different stages: (1) identification of the risks and hazards; (2) design, implementation, and evaluation of patient safety practices; and (3) maintaining vigilance to ensure that a safe environment continues and patient safety cultures remain in place. Clearly, different research methods and approaches are needed at each of the different stages of the continuum. A number of research approaches can be used at stage 1 to identify risks and hazards including the use of medical records and administrative record review, event reporting, direct observation, process mapping, focus groups, probabilistic risk assessment, and safety culture assessment. No single method can be universally applied to identify risks and hazards in patient safety. Rather, multiple approaches using combinations of these methods should be used to increase identification of risks and hazards of health care associated injury or harm to patients. PMID:14645888

  16. Patient-tailored plate for bone fixation and accurate 3D positioning in corrective osteotomy.

    PubMed

    Dobbe, J G G; Vroemen, J C; Strackee, S D; Streekstra, G J

    2013-02-01

    A bone fracture may lead to malunion of bone segments, which gives discomfort to the patient and may lead to chronic pain, reduced function and finally to early osteoarthritis. Corrective osteotomy is a treatment option to realign the bone segments. In this procedure, the surgeon tries to improve alignment by cutting the bone at, or near, the fracture location and fixates the bone segments in an improved position, using a plate and screws. Three-dimensional positioning is very complex and difficult to plan, perform and evaluate using standard 2D fluoroscopy imaging. This study introduces a new technique that uses preoperative 3D imaging to plan positioning and design a patient-tailored fixation plate that only fits in one way and realigns the bone segments as planned. The method is evaluated using artificial bones and renders realignment highly accurate and very reproducible (d(err) < 1.2 ± 0.8 mm and φ(err) < 1.8° ± 2.1°). Application of a patient-tailored plate is expected to be of great value for future corrective osteotomy surgeries.

  17. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

    PubMed Central

    Testani, Jeffrey M.; Hanberg, Jennifer S.; Cheng, Susan; Rao, Veena; Onyebeke, Chukwuma; Laur, Olga; Kula, Alexander; Chen, Michael; Wilson, F. Perry; Darlington, Andrew; Bellumkonda, Lavanya; Jacoby, Daniel; Tang, W. H. Wilson; Parikh, Chirag R.

    2015-01-01

    Background Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure (ADHF) and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Methods and Results Based on well-established renal physiologic principles an equation was derived to predict net sodium output using a spot urine sample obtained one or two hours following loop diuretic administration. This equation was then prospectively validated in 50 ADHF patients using meticulously obtained timed 6-hour urine collections to quantitate loop diuretic induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91, p<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (AUC=0.95, 95% CI 0.89–1.0, p<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66, p<0.001) and lesser ability to predict poor natriuretic response (AUC=0.76, 95% CI 0.63–0.89, p=0.002). Conclusions In patients being treated for ADHF, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample. PMID:26721915

  18. Using mixed methods to identify factors influencing patient flow.

    PubMed

    Van Vaerenbergh, Cindy

    2009-11-01

    An effective method of identifying operational factors that influence patient flow can potentially lead to improvements and thus have huge benefits on the efficiency of hospital departments. This paper presents a new inductive mixed-method approach to identify operational factors that influence patient flow through an accident and emergency (A&E) department. Preliminary explorative observations were conducted, followed by semi-structured interviews with key stakeholders. A questionnaire survey of all medical, nursing, porter and clerical staff was then conducted. The observations provided factors for further exploration: skill-mix, long working hours, equipment availability, lack of orientation programmes, inefficient IT use and issues regarding communication structures. Interviewees highlighted several factors, including availability of medical supervision and senior nursing staff, nursing documentation issues, lack of morale due to overcrowding, personality differences and factors relating to the department layout. The questionnaire respondents strongly supported the importance of the previously identified factors. This paper demonstrates an effective mixed-method approach that can be replicated by other health-care managers to identify factors influencing patient flow. Further benefits include increased volume and quality of data, increased staff awareness for the influence of internal factors on patient flow and enhancing the evidence base for future decision making when prioritizing A&E projects.

  19. Can a Rescuer or Simulated Patient Accurately Assess Motion During Cervical Spine Stabilization Practice Sessions?

    PubMed Central

    Shrier, Ian; Boissy, Patrick; Brière, Simon; Mellette, Jay; Fecteau, Luc; Matheson, Gordon O.; Garza, Daniel; Meeuwisse, Willem H.; Segal, Eli; Boulay, John; Steele, Russell J.

    2012-01-01

    Context: Health care providers must be prepared to manage all potential spine injuries as if they are unstable. Therefore, most sport teams devote resources to training for sideline cervical spine (C-spine) emergencies. Objective: To determine (1) how accurately rescuers and simulated patients can assess motion during C-spine stabilization practice and (2) whether providing performance feedback to rescuers influences their choice of stabilization technique. Design: Crossover study. Setting: Training studio. Patients or Other Participants: Athletic trainers, athletic therapists, and physiotherapists experienced at managing suspected C-spine injuries. Intervention(s): Twelve lead rescuers (at the patient's head) performed both the head-squeeze and trap-squeeze C-spine stabilization maneuvers during 4 test scenarios: lift-and-slide and log-roll placement on a spine board and confused patient trying to sit up or rotate the head. Main Outcome Measure(s): Interrater reliability between rescuer and simulated patient quality scores for subjective evaluation of C-spine stabilization during trials (0 = best, 10 = worst), correlation between rescuers' quality scores and objective measures of motion with inertial measurement units, and frequency of change in preference for the head-squeeze versus trap-squeeze maneuver. Results: Although the weighted κ value for interrater reliability was acceptable (0.71–0.74), scores varied by 2 points or more between rescuers and simulated patients for approximately 10% to 15% of trials. Rescuers' scores correlated with objective measures, but variability was large: 38% of trials scored as 0 or 1 by the rescuer involved more than 10° of motion in at least 1 direction. Feedback did not affect the preference for the lift-and-slide placement. For the log-roll placement, 6 of 8 participants who preferred the head squeeze at baseline preferred the trap squeeze after feedback. For the confused patient, 5 of 5 participants initially preferred

  20. Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients

    PubMed Central

    Smith, Ashley D.; Zhang, Yan; Barber, Robert C.; Minshall, Christian T.; Huebinger, Ryan M.

    2016-01-01

    The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients. PMID:27898681

  1. Learning Clinical Workflows to Identify Subgroups of Heart Failure Patients.

    PubMed

    Yan, Chao; Chen, You; Li, Bo; Liebovitz, David; Malin, Bradley

    2016-01-01

    Heart Failure (HF) is one of the most common indications for readmission to the hospital among elderly patients. This is due to the progressive nature of the disease, as well as its association with complex comorbidities (e.g., anemia, chronic kidney disease, chronic obstructive pulmonary disease, hyper- and hypothyroidism), which contribute to increased morbidity and mortality, as well as a reduced quality of life. Healthcare organizations (HCOs) have established diverse treatment plans for HF patients, but such routines are not always formalized and may, in fact, arise organically as a patient's management evolves over time. This investigation was motivated by the hypothesis that patients associated with a certain subgroup of HF should follow a similar workflow that, once made explicit, could be leveraged by an HCO to more effectively allocate resources and manage HF patients. Thus, in this paper, we introduce a method to identify subgroups of HF through a similarity analysis of event sequences documented in the clinical setting. Specifically, we 1) structure event sequences for HF patients based on the patterns of electronic medical record (EMR) system utilization, 2) identify subgroups of HF patients by applying a k-means clustering algorithm on utilization patterns, 3) learn clinical workflows for each subgroup, and 4) label each subgroup with diagnosis and procedure codes that are distinguishing in the set of all subgroups. To demonstrate its potential, we applied our method to EMR event logs for 785 HF inpatient stays over a 4 month period at a large academic medical center. Our method identified 8 subgroups of HF, each of which was found to associate with a canonical workflow inferred through an inductive mining algorithm. Each subgroup was further confirmed to be affiliated with specific comorbidities, such as hyperthyroidism and hypothyroidism.

  2. Genomic Models of Short-Term Exposure Accurately Predict Long-Term Chemical Carcinogenicity and Identify Putative Mechanisms of Action

    PubMed Central

    Gusenleitner, Daniel; Auerbach, Scott S.; Melia, Tisha; Gómez, Harold F.; Sherr, David H.; Monti, Stefano

    2014-01-01

    Background Despite an overall decrease in incidence of and mortality from cancer, about 40% of Americans will be diagnosed with the disease in their lifetime, and around 20% will die of it. Current approaches to test carcinogenic chemicals adopt the 2-year rodent bioassay, which is costly and time-consuming. As a result, fewer than 2% of the chemicals on the market have actually been tested. However, evidence accumulated to date suggests that gene expression profiles from model organisms exposed to chemical compounds reflect underlying mechanisms of action, and that these toxicogenomic models could be used in the prediction of chemical carcinogenicity. Results In this study, we used a rat-based microarray dataset from the NTP DrugMatrix Database to test the ability of toxicogenomics to model carcinogenicity. We analyzed 1,221 gene-expression profiles obtained from rats treated with 127 well-characterized compounds, including genotoxic and non-genotoxic carcinogens. We built a classifier that predicts a chemical's carcinogenic potential with an AUC of 0.78, and validated it on an independent dataset from the Japanese Toxicogenomics Project consisting of 2,065 profiles from 72 compounds. Finally, we identified differentially expressed genes associated with chemical carcinogenesis, and developed novel data-driven approaches for the molecular characterization of the response to chemical stressors. Conclusion Here, we validate a toxicogenomic approach to predict carcinogenicity and provide strong evidence that, with a larger set of compounds, we should be able to improve the sensitivity and specificity of the predictions. We found that the prediction of carcinogenicity is tissue-dependent and that the results also confirm and expand upon previous studies implicating DNA damage, the peroxisome proliferator-activated receptor, the aryl hydrocarbon receptor, and regenerative pathology in the response to carcinogen exposure. PMID:25058030

  3. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

    PubMed Central

    Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

    2016-01-01

    In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

  4. Identifying Patients at Risk of High Healthcare Utilization

    PubMed Central

    Sheets, Lincoln; Popejoy, Lori; APRN, GCNS-BC; Khalilia, Mohammed; Petroski, Greg; Parker, Jerry C.

    2016-01-01

    Objective. To develop a systematic and reproducible way to identify patients at increased risk for higher healthcare costs. Methods. Medical records were analyzed for 9,581 adults who were primary care patients in the University of Missouri Health System and who were enrolled in Medicare or Medicaid. Patients were categorized into one of four risk tiers as of October 1, 2013, and the four tiers were compared on demographic characteristics, number of healthcare episodes, and healthcare charges in the year before and the year after cohort formation. Results. The mean number of healthcare episodes and the sum of healthcare charges in the year following cohort formation were higher for patients in the higher-risk tiers. Conclusions. Retrospective information that is easily extracted from medical records can be used to create risk tiers that provide highly useful information about the prospective risk of healthcare utilization and costs. PMID:28269910

  5. Learning Clinical Workflows to Identify Subgroups of Heart Failure Patients

    PubMed Central

    Yan, Chao; Chen, You; Li, Bo; Liebovitz, David; Malin, Bradley

    2016-01-01

    Heart Failure (HF) is one of the most common indications for readmission to the hospital among elderly patients. This is due to the progressive nature of the disease, as well as its association with complex comorbidities (e.g., anemia, chronic kidney disease, chronic obstructive pulmonary disease, hyper- and hypothyroidism), which contribute to increased morbidity and mortality, as well as a reduced quality of life. Healthcare organizations (HCOs) have established diverse treatment plans for HF patients, but such routines are not always formalized and may, in fact, arise organically as a patient’s management evolves over time. This investigation was motivated by the hypothesis that patients associated with a certain subgroup of HF should follow a similar workflow that, once made explicit, could be leveraged by an HCO to more effectively allocate resources and manage HF patients. Thus, in this paper, we introduce a method to identify subgroups of HF through a similarity analysis of event sequences documented in the clinical setting. Specifically, we 1) structure event sequences for HF patients based on the patterns of electronic medical record (EMR) system utilization, 2) identify subgroups of HF patients by applying a k-means clustering algorithm on utilization patterns, 3) learn clinical workflows for each subgroup, and 4) label each subgroup with diagnosis and procedure codes that are distinguishing in the set of all subgroups. To demonstrate its potential, we applied our method to EMR event logs for 785 HF inpatient stays over a 4 month period at a large academic medical center. Our method identified 8 subgroups of HF, each of which was found to associate with a canonical workflow inferred through an inductive mining algorithm. Each subgroup was further confirmed to be affiliated with specific comorbidities, such as hyperthyroidism and hypothyroidism. PMID:28269922

  6. Clinical assessment tools identify functional deficits in fragility fracture patients

    PubMed Central

    Ames, Tyler D; Wee, Corinne E; Le, Khoi M; Wang, Tiffany L; Bishop, Julie Y; Phieffer, Laura S; Quatman, Carmen E

    2016-01-01

    Purpose To identify inexpensive, noninvasive, portable, clinical assessment tools that can be used to assess functional performance measures that may put older patients at risk for falls such as balance, handgrip strength, and lumbopelvic control. Patients and methods Twenty fragility fracture patients and 21 healthy control subjects were evaluated using clinical assessment tools (Nintendo Wii Balance Board [WBB], a handheld dynamometer, and an application for the Apple iPod Touch, the Level Belt) that measure functional performance during activity of daily living tasks. The main outcome measurements were balance (WBB), handgrip strength (handheld dynamometer), and lumbopelvic control (iPod Touch Level Belt), which were compared between fragility fracture patients and healthy controls. Results Fragility fracture patients had lower scores on the vertical component of the WBB Torso Twist task (P=0.042) and greater medial–lateral lumbopelvic sway during a 40 m walk (P=0.026) when compared to healthy controls. Unexpectedly, the fracture patients had significantly higher scores on the left leg (P=0.020) and total components (P=0.010) of the WBB Single Leg Stand task as well as less faults during the left Single Leg Stand task (P=0.003). Conclusion The clinical assessment tools utilized in this study are relatively inexpensive and portable tools of performance measures capable of detecting differences in postural sway between fragility fracture patients and controls. PMID:27217738

  7. Identifying older diabetic patients at risk of poor glycemic control

    PubMed Central

    Incalzi, Raffaele Antonelli; Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Carosella, Luciana; Mazzei, Bruno; Perticone, Francesco; Carbonin, PierUgo

    2002-01-01

    Background Optimal glycemic control prevents the onset of diabetes complications. Identifying diabetic patients at risk of poor glycemic control could help promoting dedicated interventions. The purpose of this study was to identify predictors of poor short-term and long-term glycemic control in older diabetic in-patients. Methods A total of 1354 older diabetic in-patients consecutively enrolled in a multicenter study formed the training population (retrospective arm); 264 patients consecutively admitted to a ward of general medicine formed the testing population (prospective arm). Glycated hemoglobin (HbA1c) was measured on admission and one year after the discharge in the testing population. Independent correlates of a discharge glycemia ≥ 140 mg/dl in the training population were assessed by logistic regression analysis and a clinical prediction rule was developed. The ability of the prediction rule and that of admission HbA1c to predict discharge glycemia ≥ 140 mg/dl and HbA1c > 7% one year after discharge was assessed in the testing population. Results Selected admission variables (diastolic arterial pressure < 80 mmHg, glycemia = 143–218 mg/dl, glycemia > 218 mg/dl, history of insulinic or combined hypoglycemic therapy, Charlson's index > 2) were combined to obtain a score predicting a discharge fasting glycemia ≥ 140 mg/dl in the training population. A modified score was obtained by adding 1 if admission HbA1c exceeded 7.8%. The modified score was the best predictor of both discharge glycemia ≥ 140 mg/dl (sensitivity = 79%, specificity = 63%) and 1 year HbA1c > 7% (sensitivity = 72%, specificity = 71%) in the testing population. Conclusion A simple clinical prediction rule might help identify older diabetic in-patients at risk of both short and long term poor glycemic control. PMID:12194701

  8. Identifying and managing patients with delirium in acute care settings.

    PubMed

    Bond, Penny; Goudie, Karen

    2015-11-01

    Delirium is an acute medical emergency affecting about one in eight acute hospital inpatients. It is associated with poor outcomes, is more prevalent in older people and it is estimated that half of all patients receiving intensive care or surgery for a hip fracture will be affected. Despite its prevalence and impact, delirium is not reliably identified or well managed. Improving the identification and management of patients with delirium has been a focus for the national improving older people's acute care work programme in NHS Scotland. A delirium toolkit has been developed, which includes the 4AT rapid assessment test, information for patients and carers and a care bundle for managing delirium based on existing guidance. This toolkit has been tested and implemented by teams from a range of acute care settings to support improvements in the identification and immediate management of delirium.

  9. Contrast-enhanced ultrasound improves accurate identification of appendiceal mucinous adenocarcinoma in an old patient

    PubMed Central

    Shang, Jing; Ruan, Li-tao; Dang, Ying; Wang, Yun-yue; Song, Yan; Lian, Jie

    2016-01-01

    Abstract Background: Adenocarcinoma of appendiceal origin is far rarer than other colorectal carcinomas and its preoperative diagnosis is challenging. To our knowledge, utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. Method: A 61-year-old man presented with abdominal pain in the right lower quadrant for 20 days. In order to fulfill an accurately preoperative diagnosis, he received laboratory and imaging tests such as carcinoembryonic antigen (CEA), computer tomography (CT), CEUS and endoscope. Diagnosis and Intervention: He was initially suspected of suffering appendicitis, while his white blood cell count was normal and carcinoembryonic antigen (CEA) in serum was remarkably increased. Both routine ultrasound and computer tomography (CT) examinations supported suppurative appendicitis. The overall data, however, failed to excluded neoplastic pathology thoroughly. Therefore, CEUS was carried out and showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The result of the follow-up biopsy guided by endoscope was consistent with appendiceal tumor. The patient received laparoscopic right hemicolectomy. Histopathology confirmed as well differentiated mucinous adenocarcinoma of appendix origin. His postoperative course was uneventful, and he had a regular diet again without any complaint. Result: Serum CEA was remarkably increased (12.00 ng/mL). Both routine ultrasound and CT examinations supported suppurative appendicitis. However, CEUS examination showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The follow-up biopsy guided by endoscope and surgical specimens confirmed as well differentiated mucinous adenocarcinoma of appendix origin. Conclusion: Most mucinous adenocarcinoma mimicking appendicitis results in difficult diagnosis preoperatively. Clinician and radiologist should be

  10. Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients

    PubMed Central

    Mock, Andreas; Warta, Rolf; Geisenberger, Christoph; Bischoff, Ralf; Schulte, Alexander; Lamszus, Katrin; Stadler, Volker; Felgenhauer, Thomas; Schichor, Christian; Schwartz, Christoph; Matschke, Jakob; Jungk, Christine; Ahmadi, Rezvan; Sahm, Felix; Capper, David; Glass, Rainer; Tonn, Jörg-Christian; Westphal, Manfred; von Deimling, Andreas; Unterberg, Andreas; Bermejo, Justo Lorenzo; Herold-Mende, Christel

    2015-01-01

    Liquid biopsies come of age offering unexploited potential to monitor and react to tumor evolution. We developed a cost-effective assay to non-invasively determine the immune status of glioblastoma (GBM) patients. Employing newly developed printed peptide microarrays we assessed the B-cell response against tumor-associated antigens (TAAs) in 214 patients. Firstly, sera of long-term (36+ months, LTS, n=10) and short-term (6-10 months, STS, n=14) surviving patients were screened for prognostic antibodies against 1745 13-mer peptides covering known TAAs (TNC, EGFR, GLEA2, PHF3, FABP5, MAGEA3). Next, survival associations were investigated in two retrospective independent multicenter validation sets (n=61, n=129, all IDH1-wildtype). Reliability of measurements was tested using a second array technology (spotted arrays). LTS/STS screening analyses identified 106 differential antibody responses. Evaluating the Top30 peptides in validation set 1 revealed three prognostic peptides. Prediction of TNC peptide VCEDGFTGPDCAE was confirmed in a second set (p=0.043, HR=0.66 [0.44-0.99]) and was unrelated to TNC protein expression. Median signals of printed arrays correlated with pre-synthesized spotted microarrays (p<0.0002, R=0.33). Multiple survival analysis revealed independence of age, gender, KPI and MGMT status. We present a novel peptide microarray immune assay that identified increased anti-TNC VCEDGFTGPDCAE serum antibody titer as a promising non-invasive biomarker for prolonged survival. PMID:25944688

  11. Accuracy of administrative data for identifying patients with pneumonia.

    PubMed

    Aronsky, Dominik; Haug, Peter J; Lagor, Charles; Dean, Nathan C

    2005-01-01

    The goal of this study was to determine the accuracy and the impact of 5 different claims-based pneumonia definitions. Three International Classification of Diseases, Version 9, (ICD-9), and 2 diagnosis-related group (DRG)-based case identification algorithms were compared against an independent, clinical pneumonia reference standard. Among 10748 patients, 272 (2.5%) had pneumonia verified by the reference standard. The sensitivity of claims-based algorithms ranged from 47.8% to 66.2%. The positive predictive values ranged from 72.6% to 80.8%. Patient-related variables were not significantly different from the reference standard among the 3 ICD-9-based algorithms. DRG-based algorithms had significantly lower hospital admission rates (57% and 65% vs 73.2%), lower 30-day mortality (5.0% and 5.8% vs 10.7%), shorter length of stay (3.9 and 4.1 days vs 5.6 days), and lower costs (USD $4543 and USD $5159 vs USD $8585). Claims-based identification algorithms for defining pneumonia in administrative databases are imprecise. ICD-9-based algorithms did not influence patient variables in our population. Identifying pneumonia patients with DRG codes is significantly less precise.

  12. Identifying fallers among ophthalmic patients using classification tree methodology

    PubMed Central

    Chirico, Franco; Pecchia, Leandro; Rossi, Settimio; Testa, Francesco; Simonelli, Francesca

    2017-01-01

    Purpose To develop and validate a tool aiming to support ophthalmologists in identifying, during routine ophthalmologic visits, patients at higher risk of falling in the following year. Methods A group of 141 subjects (age: 73.2 ± 11.4 years), recruited at our Eye Clinic, underwent a baseline ophthalmic examination and a standardized questionnaire, including lifestyles, general health, social engagement and eyesight problems. Moreover, visual disability was assessed by the Activity of Daily Vision Scale (ADVS). The subjects were followed up for 12 months in order to record prospective falls. A subject who reported at least one fall within one year from the baseline assessment was considered as faller, otherwise as non-faller. Different tree-based algorithms (i.e., C4.5, AdaBoost and Random Forests) were used to develop automatic classifiers and their performances were evaluated by the cross-validation approach. Results Over the follow-up, 25 falls were referred by 13 patients. The logistic regression analysis showed the following variables as significant predictors of prospective falls: pseudophakia and use of prescribed eyeglasses as protective factors, recent worsening of visual acuity as risk factor. Random Forest ranked best corrected visual acuity, number of sleeping hours and job type as the most important features. Finally, AdaBoost enabled the identification of subjects at higher risk of falling in the following 12 months with a sensitivity rate of 69.2% and a specificity rate of 76.6%. Conclusions The current study proposes a novel method, based on classification trees applied to self-reported factors and health information assessed by a standardized questionnaire during ophthalmological visits, to identify ophthalmic patients at higher risk of falling in the following 12 months. The findings of the current study pave the way to the validation of the proposed novel tool for fall risk screening on a larger cohort of patients with visual impairment referred

  13. Rare variant mutations identified in pediatric patients with dilated cardiomyopathy

    PubMed Central

    Rampersaud, Evadnie; Siegfried, Jill D; Norton, Nadine; Li, Duanxiang; Martin, Eden; Hershberger, Ray E

    2010-01-01

    Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18 years of age who underwent detailed clinical and genetic evaluation, and summarize here the evidence for mutations causing DCM in these cases from 15 genes (PSEN1, PSEN2, CSRP3, LBD3, MYH7, SCN5A, TCAP, TNNT2, LMNA, MYBPC3, MYH6, TNNC1, TNNI3, TPM1, and RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1 year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2 weeks, 9 and 13 years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in TPM1 (32%) and TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1 year of age, 3 had mutations in TPM1 (including a set of identical twins), 1 in TNNT2, 1 in MYH7, and 1 with multiple mutations (MYH7 and TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause. PMID:21483645

  14. A software tool for removing patient identifying information from clinical documents.

    PubMed

    Friedlin, F Jeff; McDonald, Clement J

    2008-01-01

    We created a software tool that accurately removes all patient identifying information from various kinds of clinical data documents, including laboratory and narrative reports. We created the Medical De-identification System (MeDS), a software tool that de-identifies clinical documents, and performed 2 evaluations. Our first evaluation used 2,400 Health Level Seven (HL7) messages from 10 different HL7 message producers. After modifying the software based on the results of this first evaluation, we performed a second evaluation using 7,190 pathology report HL7 messages. We compared the results of MeDS de-identification process to a gold standard of human review to find identifying strings. For both evaluations, we calculated the number of successful scrubs, missed identifiers, and over-scrubs committed by MeDS and evaluated the readability and interpretability of the scrubbed messages. We categorized all missed identifiers into 3 groups: (1) complete HIPAA-specified identifiers, (2) HIPAA-specified identifier fragments, (3) non-HIPAA-specified identifiers (such as provider names and addresses). In the results of the first-pass evaluation, MeDS scrubbed 11,273 (99.06%) of the 11,380 HIPAA-specified identifiers and 38,095 (98.26%) of the 38,768 non-HIPAA-specified identifiers. In our second evaluation (status postmodification to the software), MeDS scrubbed 79,993 (99.47%) of the 80,418 HIPAA-specified identifiers and 12,689 (96.93%) of the 13,091 non-HIPAA-specified identifiers. Approximately 95% of scrubbed messages were both readable and interpretable. We conclude that MeDS successfully de-identified a wide range of medical documents from numerous sources and creates scrubbed reports that retain their interpretability, thereby maintaining their usefulness for research.

  15. Identifying Patients with Depression Using Free-text Clinical Documents.

    PubMed

    Zhou, Li; Baughman, Amy W; Lei, Victor J; Lai, Kenneth H; Navathe, Amol S; Chang, Frank; Sordo, Margarita; Topaz, Maxim; Zhong, Feiran; Murrali, Madhavan; Navathe, Shamkant; Rocha, Roberto A

    2015-01-01

    About 1 in 10 adults are reported to exhibit clinical depression and the associated personal, societal, and economic costs are significant. In this study, we applied the MTERMS NLP system and machine learning classification algorithms to identify patients with depression using discharge summaries. Domain experts reviewed both the training and test cases, and classified these cases as depression with a high, intermediate, and low confidence. For depression cases with high confidence, all of the algorithms we tested performed similarly, with MTERMS' knowledge-based decision tree slightly better than the machine learning classifiers, achieving an F-measure of 89.6%. MTERMS also achieved the highest F-measure (70.6%) on intermediate confidence cases. The RIPPER rule learner was the best performing machine learning method, with an F-measure of 70.0%, and a higher precision but lower recall than MTERMS. The proposed NLP-based approach was able to identify a significant portion of the depression cases (about 20%) that were not on the coded diagnosis list.

  16. Identifying Causal Risk Factors for Violence among Discharged Patients

    PubMed Central

    Coid, Jeremy W.; Kallis, Constantinos; Doyle, Mike; Shaw, Jenny; Ullrich, Simone

    2015-01-01

    Background Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. Methods We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. Results In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85–12.65, P<0.001), instability (OR 5.41, 95% CI 3.44–8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21–16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08–0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. Conclusions Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors

  17. Using computer modeling to help identify patient subgroups in clinical data repositories.

    PubMed Central

    Cooper, G. F.; Buchanan, B. G.; Kayaalp, M.; Saul, M.; Vries, J. K.

    1998-01-01

    OBJECTIVE: The ability to accurately and efficiently identify patient cases of interest in a hospital information system has many important clinical, research, educational and administrative uses. The identification of cases of interest sometimes can be difficult. This paper describes a two-stage method for searching for cases of interest. DESIGN: First, a Boolean search is performed using coded database variables. The user classifies the retrieved cases as being of interest or not. Second, based on the user-classified cases, a computer model of the patient cases of interest is constructed. The model is then used to help locate additional cases. These cases provide an augmented training set for constructing a new computer model of the cases of interest. This cycle of modeling and user classification continues until halted by the user. MEASUREMENTS: This paper describes a pilot study in which this method is used to identify the records of patients who have venous thrombosis. RESULTS: The results indicate that computer modeling enhances the identification of patient cases of interest. PMID:9929206

  18. New approach based on tetrahedral-mesh geometry for accurate 4D Monte Carlo patient-dose calculation.

    PubMed

    Han, Min Cheol; Yeom, Yeon Soo; Kim, Chan Hyeong; Kim, Seonghoon; Sohn, Jason W

    2015-02-21

    In the present study, to achieve accurate 4D Monte Carlo dose calculation in radiation therapy, we devised a new approach that combines (1) modeling of the patient body using tetrahedral-mesh geometry based on the patient's 4D CT data, (2) continuous movement/deformation of the tetrahedral patient model by interpolation of deformation vector fields acquired through deformable image registration, and (3) direct transportation of radiation particles during the movement and deformation of the tetrahedral patient model. The results of our feasibility study show that it is certainly possible to construct 4D patient models (= phantoms) with sufficient accuracy using the tetrahedral-mesh geometry and to directly transport radiation particles during continuous movement and deformation of the tetrahedral patient model. This new approach not only produces more accurate dose distribution in the patient but also replaces the current practice of using multiple 3D voxel phantoms and combining multiple dose distributions after Monte Carlo simulations. For routine clinical application of our new approach, the use of fast automatic segmentation algorithms is a must. In order to achieve, simultaneously, both dose accuracy and computation speed, the number of tetrahedrons for the lungs should be optimized. Although the current computation speed of our new 4D Monte Carlo simulation approach is slow (i.e. ~40 times slower than that of the conventional dose accumulation approach), this problem is resolvable by developing, in Geant4, a dedicated navigation class optimized for particle transportation in tetrahedral-mesh geometry.

  19. Outpatient Preoperative Education Needs Identified by Nurses and Patients.

    DTIC Science & Technology

    2007-11-02

    Quality of care can be measured by outcomes that are a result of patient education . The emphasis on ambulatory surgery and the accompanying minimum lengths...34, "move them out" routine may perpetuate insensitivity to patients, decrease patient education , and distance nurses from realizing what is most...important to their patients. The Joint Commission on Accreditation of Healthcare Organizations Standards (JCAHO) (1997) state the goal of patient education is

  20. New approach based on tetrahedral-mesh geometry for accurate 4D Monte Carlo patient-dose calculation

    NASA Astrophysics Data System (ADS)

    Han, Min Cheol; Yeom, Yeon Soo; Kim, Chan Hyeong; Kim, Seonghoon; Sohn, Jason W.

    2015-02-01

    In the present study, to achieve accurate 4D Monte Carlo dose calculation in radiation therapy, we devised a new approach that combines (1) modeling of the patient body using tetrahedral-mesh geometry based on the patient’s 4D CT data, (2) continuous movement/deformation of the tetrahedral patient model by interpolation of deformation vector fields acquired through deformable image registration, and (3) direct transportation of radiation particles during the movement and deformation of the tetrahedral patient model. The results of our feasibility study show that it is certainly possible to construct 4D patient models (= phantoms) with sufficient accuracy using the tetrahedral-mesh geometry and to directly transport radiation particles during continuous movement and deformation of the tetrahedral patient model. This new approach not only produces more accurate dose distribution in the patient but also replaces the current practice of using multiple 3D voxel phantoms and combining multiple dose distributions after Monte Carlo simulations. For routine clinical application of our new approach, the use of fast automatic segmentation algorithms is a must. In order to achieve, simultaneously, both dose accuracy and computation speed, the number of tetrahedrons for the lungs should be optimized. Although the current computation speed of our new 4D Monte Carlo simulation approach is slow (i.e. ~40 times slower than that of the conventional dose accumulation approach), this problem is resolvable by developing, in Geant4, a dedicated navigation class optimized for particle transportation in tetrahedral-mesh geometry.

  1. Accurate positioning for head and neck cancer patients using 2D and 3D image guidance

    PubMed Central

    Kang, Hyejoo; Lovelock, Dale M.; Yorke, Ellen D.; Kriminiski, Sergey; Lee, Nancy; Amols, Howard I.

    2011-01-01

    Our goal is to determine an optimized image-guided setup by comparing setup errors determined by two-dimensional (2D) and three-dimensional (3D) image guidance for head and neck cancer (HNC) patients immobilized by customized thermoplastic masks. Nine patients received weekly imaging sessions, for a total of 54, throughout treatment. Patients were first set up by matching lasers to surface marks (initial) and then translationally corrected using manual registration of orthogonal kilovoltage (kV) radiographs with DRRs (2D-2D) on bony anatomy. A kV cone beam CT (kVCBCT) was acquired and manually registered to the simulation CT using only translations (3D-3D) on the same bony anatomy to determine further translational corrections. After treatment, a second set of kVCBCT was acquired to assess intrafractional motion. Averaged over all sessions, 2D-2D registration led to translational corrections from initial setup of 3.5 ± 2.2 (range 0–8) mm. The addition of 3D-3D registration resulted in only small incremental adjustment (0.8 ± 1.5 mm). We retrospectively calculated patient setup rotation errors using an automatic rigid-body algorithm with 6 degrees of freedom (DoF) on regions of interest (ROI) of in-field bony anatomy (mainly the C2 vertebral body). Small rotations were determined for most of the imaging sessions; however, occasionally rotations > 3° were observed. The calculated intrafractional motion with automatic registration was < 3.5 mm for eight patients, and < 2° for all patients. We conclude that daily manual 2D-2D registration on radiographs reduces positioning errors for mask-immobilized HNC patients in most cases, and is easily implemented. 3D-3D registration adds little improvement over 2D-2D registration without correcting rotational errors. We also conclude that thermoplastic masks are effective for patient immobilization. PMID:21330971

  2. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    SciTech Connect

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-07-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

  3. 4D laser camera for accurate patient positioning, collision avoidance, image fusion and adaptive approaches during diagnostic and therapeutic procedures.

    PubMed

    Brahme, Anders; Nyman, Peter; Skatt, Björn

    2008-05-01

    A four-dimensional (4D) laser camera (LC) has been developed for accurate patient imaging in diagnostic and therapeutic radiology. A complementary metal-oxide semiconductor camera images the intersection of a scanned fan shaped laser beam with the surface of the patient and allows real time recording of movements in a three-dimensional (3D) or four-dimensional (4D) format (3D +time). The LC system was first designed as an accurate patient setup tool during diagnostic and therapeutic applications but was found to be of much wider applicability as a general 4D photon "tag" for the surface of the patient in different clinical procedures. It is presently used as a 3D or 4D optical benchmark or tag for accurate delineation of the patient surface as demonstrated for patient auto setup, breathing and heart motion detection. Furthermore, its future potential applications in gating, adaptive therapy, 3D or 4D image fusion between most imaging modalities and image processing are discussed. It is shown that the LC system has a geometrical resolution of about 0, 1 mm and that the rigid body repositioning accuracy is about 0, 5 mm below 20 mm displacements, 1 mm below 40 mm and better than 2 mm at 70 mm. This indicates a slight need for repeated repositioning when the initial error is larger than about 50 mm. The positioning accuracy with standard patient setup procedures for prostate cancer at Karolinska was found to be about 5-6 mm when independently measured using the LC system. The system was found valuable for positron emission tomography-computed tomography (PET-CT) in vivo tumor and dose delivery imaging where it potentially may allow effective correction for breathing artifacts in 4D PET-CT and image fusion with lymph node atlases for accurate target volume definition in oncology. With a LC system in all imaging and radiation therapy rooms, auto setup during repeated diagnostic and therapeutic procedures may save around 5 min per session, increase accuracy and allow

  4. Accurate Monitoring Leads to Effective Control and Greater Learning of Patient Education Materials

    ERIC Educational Resources Information Center

    Rawson, Katherine A.; O'Neil, Rochelle; Dunlosky, John

    2011-01-01

    Effective management of chronic diseases (e.g., diabetes) can depend on the extent to which patients can learn and remember disease-relevant information. In two experiments, we explored a technique motivated by theories of self-regulated learning for improving people's learning of information relevant to managing a chronic disease. Materials were…

  5. Molecular Characterization of Trichomonas vaginalis Strains Based on Identifying Their Probable Variations in Asymptomatic Patients

    PubMed Central

    SPOTIN, Adel; EGHTEDAR, Sanaz TAGHIZADEH; SHAHBAZI, Abbas; SALEHPOUR, Asghar; SARAFRAZ, Seddigheh; SHARIATZADEH, Seyyed Ali; MAHAMI-OSKOUEI, Mahmoud

    2016-01-01

    Background: The aim of this study was to identify the Trichomonas vaginalis strains/haplotypes based on identifying their probable variations in asymptomatic patients referred to Tabriz health centers, northwestern Iran. Methods: Sampling was taken from 50-suspected women to T. vaginalis in northwestern Iran. The obtained samples were smeared and cultured. Fifty DNA samples were extracted, amplified and identified by nested polymerase chain reaction and PCR-RFLP of actin gene using two endonuclease enzymes: MseI and RsaI. To reconfirm, the amplicons of actin gene were directly sequenced in order to identify the strains/haplotypes. Results: PCR-RFLP patterns, sequencing and phylogenetic analyses revealed definitely the presence of the G (n=22; 73.4%) and E (n=8; 26.6%) strains. Multiple alignments findings of genotype G showed five haplotypes and two amino acid substitutions in codons 192 and 211 although, no remarkable unique haplotype was found in genotype E. Conclusion: The accurate identification of T. vaginalis strains based on discrimination of their unknown haplotypes particularly those which are impacted on protein translation should be considered in parasite status, drug resistance, mixed infection with HIV and monitoring of asymptomatic trichomoniasis in the region. PMID:28127362

  6. An accurate, simple prognostic model consisting of age, JAK2, CALR, and MPL mutation status for patients with primary myelofibrosis

    PubMed Central

    Rozovski, Uri; Verstovsek, Srdan; Manshouri, Taghi; Dembitz, Vilma; Bozinovic, Ksenija; Newberry, Kate; Zhang, Ying; Bove, Joseph E.; Pierce, Sherry; Kantarjian, Hagop; Estrov, Zeev

    2017-01-01

    In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia genes have a favorable outcome, and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging due to the heterogeneous survival of patients with mutated Janus kinase 2. To develop a prognostic model based on mutation status, we screened primary myelofibrosis patients seen at the MD Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344 primary myelofibrosis patients, Janus kinase 2V617F was detected in 226 (66%), calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16 (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus kinase 2-mutated patients into those with high Janus kinase 2V617F allele burden and favorable survival and those with low Janus kinase 2V617F allele burden and unfavorable survival. Patients with a favorable mutation status (high Janus kinase 2V617F allele burden/myeloproliferative leukemia/calreticulin mutation) and aged 65 years or under had a median survival of 126 months. Patients with one risk factor (low Janus kinase 2V617F allele burden/triple-negative or age >65 years) had an intermediate survival duration, and patients aged over 65 years with an adverse mutation status (low Janus kinase 2V617F allele burden or triple-negative) had a median survival of only 35 months. Our simple and easily applied age- and mutation status-based scoring system accurately predicted the survival of patients with primary myelofibrosis. PMID:27686378

  7. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

  8. Identifying Patients With Sepsis on the Hospital Wards.

    PubMed

    Bhattacharjee, Poushali; Edelson, Dana P; Churpek, Matthew M

    2017-04-01

    Sepsis contributes to up to half of all deaths in hospitalized patients, and early interventions, such as appropriate antibiotics, have been shown to improve outcomes. Most research has focused on early identification and treatment of patients with sepsis in the ED and the ICU; however, many patients acquire sepsis on the general wards. The goal of this review is to discuss recent advances in the detection of sepsis in patients on the hospital wards. We discuss data highlighting the benefits and limitations of the systemic inflammatory response syndrome (SIRS) criteria for screening patients with sepsis, such as its low specificity, as well as newly described scoring systems, including the proposed role of the quick sepsis-related organ failure assessment (qSOFA) score. Challenges specific to detecting sepsis on the wards are discussed, and future directions that use big data approaches and automated alert systems are highlighted.

  9. Supporting patient screening to identify suitable clinical trials.

    PubMed

    Bucur, Anca; Van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; De Schepper, Kristof; Perez-Rey, David; Alonso-Calvo, Raul; Pugliano, Lina; Saini, Kamal

    2014-01-01

    To support the efficient execution of post-genomic multi-centric clinical trials in breast cancer we propose a solution that streamlines the assessment of the eligibility of patients for available trials. The assessment of the eligibility of a patient for a trial requires evaluating whether each eligibility criterion is satisfied and is often a time consuming and manual task. The main focus in the literature has been on proposing different methods for modelling and formalizing the eligibility criteria. However the current adoption of these approaches in clinical care is limited. Less effort has been dedicated to the automatic matching of criteria to the patient data managed in clinical care. We address both aspects and propose a scalable, efficient and pragmatic patient screening solution enabling automatic evaluation of eligibility of patients for a relevant set of trials. This covers the flexible formalization of criteria and of other relevant trial metadata and the efficient management of these representations.

  10. Patient-reported outcomes 3 months after spine surgery: is it an accurate predictor of 12-month outcome in real-world registry platforms?

    PubMed

    Parker, Scott L; Asher, Anthony L; Godil, Saniya S; Devin, Clinton J; McGirt, Matthew J

    2015-12-01

    OBJECT The health care landscape is rapidly shifting to incentivize quality of care rather than quantity of care. Quality and outcomes registry platforms lie at the center of all emerging evidence-driven reform models and will be used to inform decision makers in health care delivery. Obtaining real-world registry outcomes data from patients 12 months after spine surgery remains a challenge. The authors set out to determine whether 3-month patient-reported outcomes accurately predict 12-month outcomes and, hence, whether 3-month measurement systems suffice to identify effective versus noneffective spine care. METHODS All patients undergoing lumbar spine surgery for degenerative disease at a single medical institution over a 2-year period were enrolled in a prospective longitudinal registry. Patient-reported outcome instruments (numeric rating scale [NRS], Oswestry Disability Index [ODI], 12-Item Short Form Health Survey [SF-12], EQ-5D, and the Zung Self-Rating Depression Scale) were recorded prospectively at baseline and at 3 months and 12 months after surgery. Linear regression was performed to determine the independent association of 3- and 12-month outcome. Receiver operating characteristic (ROC) curve analysis was performed to determine whether improvement in general health state (EQ-5D) and disability (ODI) at 3 months accurately predicted improvement and achievement of minimum clinical important difference (MCID) at 12 months. RESULTS A total of 593 patients undergoing elective lumbar surgery were included in the study. There was a significant correlation between 3-month and 12-month EQ-5D (r = 0.71; p < 0.0001) and ODI (r = 0.70; p < 0.0001); however, the authors observed a sizable discrepancy in achievement of a clinically significant improvement (MCID) threshold at 3 versus 12 months on an individual patient level. For postoperative disability (ODI), 11.5% of patients who achieved an MCID threshold at 3 months dropped below this threshold at 12 months; 10

  11. Why Patient Matching Is a Challenge: Research on Master Patient Index (MPI) Data Discrepancies in Key Identifying Fields.

    PubMed

    Just, Beth Haenke; Marc, David; Munns, Megan; Sandefer, Ryan

    2016-01-01

    Patient identification matching problems are a major contributor to data integrity issues within electronic health records. These issues impede the improvement of healthcare quality through health information exchange and care coordination, and contribute to deaths resulting from medical errors. Despite best practices in the area of patient access and medical record management to avoid duplicating patient records, duplicate records continue to be a significant problem in healthcare. This study examined the underlying causes of duplicate records using a multisite data set of 398,939 patient records with confirmed duplicates and analyzed multiple reasons for data discrepancies between those record matches. The field that had the greatest proportion of mismatches (nondefault values) was the middle name, accounting for 58.30 percent of mismatches. The Social Security number was the second most frequent mismatch, occurring in 53.54 percent of the duplicate pairs. The majority of the mismatches in the name fields were the result of misspellings (53.14 percent in first name and 33.62 percent in last name) or swapped last name/first name, first name/middle name, or last name/middle name pairs. The use of more sophisticated technologies is critical to improving patient matching. However, no amount of advanced technology or increased data capture will completely eliminate human errors. Thus, the establishment of policies and procedures (such as standard naming conventions or search routines) for front-end and back-end staff to follow is foundational for the overall data integrity process. Training staff on standard policies and procedures will result in fewer duplicates created on the front end and more accurate duplicate record matching and merging on the back end. Furthermore, monitoring, analyzing trends, and identifying errors that occur are proactive ways to identify data integrity issues.

  12. Why Patient Matching Is a Challenge: Research on Master Patient Index (MPI) Data Discrepancies in Key Identifying Fields

    PubMed Central

    Just, Beth Haenke; Marc, David; Munns, Megan; Sandefer, Ryan

    2016-01-01

    Patient identification matching problems are a major contributor to data integrity issues within electronic health records. These issues impede the improvement of healthcare quality through health information exchange and care coordination, and contribute to deaths resulting from medical errors. Despite best practices in the area of patient access and medical record management to avoid duplicating patient records, duplicate records continue to be a significant problem in healthcare. This study examined the underlying causes of duplicate records using a multisite data set of 398,939 patient records with confirmed duplicates and analyzed multiple reasons for data discrepancies between those record matches. The field that had the greatest proportion of mismatches (nondefault values) was the middle name, accounting for 58.30 percent of mismatches. The Social Security number was the second most frequent mismatch, occurring in 53.54 percent of the duplicate pairs. The majority of the mismatches in the name fields were the result of misspellings (53.14 percent in first name and 33.62 percent in last name) or swapped last name/first name, first name/middle name, or last name/middle name pairs. The use of more sophisticated technologies is critical to improving patient matching. However, no amount of advanced technology or increased data capture will completely eliminate human errors. Thus, the establishment of policies and procedures (such as standard naming conventions or search routines) for front-end and back-end staff to follow is foundational for the overall data integrity process. Training staff on standard policies and procedures will result in fewer duplicates created on the front end and more accurate duplicate record matching and merging on the back end. Furthermore, monitoring, analyzing trends, and identifying errors that occur are proactive ways to identify data integrity issues. PMID:27134610

  13. Robust and Accurate Modeling Approaches for Migraine Per-Patient Prediction from Ambulatory Data.

    PubMed

    Pagán, Josué; De Orbe, M Irene; Gago, Ana; Sobrado, Mónica; Risco-Martín, José L; Mora, J Vivancos; Moya, José M; Ayala, José L

    2015-06-30

    Migraine is one of the most wide-spread neurological disorders, and its medical treatment represents a high percentage of the costs of health systems. In some patients, characteristic symptoms that precede the headache appear. However, they are nonspecific, and their prediction horizon is unknown and pretty variable; hence, these symptoms are almost useless for prediction, and they are not useful to advance the intake of drugs to be effective and neutralize the pain. To solve this problem, this paper sets up a realistic monitoring scenario where hemodynamic variables from real patients are monitored in ambulatory conditions with a wireless body sensor network (WBSN). The acquired data are used to evaluate the predictive capabilities and robustness against noise and failures in sensors of several modeling approaches. The obtained results encourage the development of per-patient models based on state-space models (N4SID) that are capable of providing average forecast windows of 47 min and a low rate of false positives.

  14. Robust and Accurate Modeling Approaches for Migraine Per-Patient Prediction from Ambulatory Data

    PubMed Central

    Pagán, Josué; Irene De Orbe, M.; Gago, Ana; Sobrado, Mónica; Risco-Martín, José L.; Vivancos Mora, J.; Moya, José M.; Ayala, José L.

    2015-01-01

    Migraine is one of the most wide-spread neurological disorders, and its medical treatment represents a high percentage of the costs of health systems. In some patients, characteristic symptoms that precede the headache appear. However, they are nonspecific, and their prediction horizon is unknown and pretty variable; hence, these symptoms are almost useless for prediction, and they are not useful to advance the intake of drugs to be effective and neutralize the pain. To solve this problem, this paper sets up a realistic monitoring scenario where hemodynamic variables from real patients are monitored in ambulatory conditions with a wireless body sensor network (WBSN). The acquired data are used to evaluate the predictive capabilities and robustness against noise and failures in sensors of several modeling approaches. The obtained results encourage the development of per-patient models based on state-space models (N4SID) that are capable of providing average forecast windows of 47 min and a low rate of false positives. PMID:26134103

  15. Patients undergoing subacute rehabilitation have accurate expectations of their health-related quality of life at discharge

    PubMed Central

    2012-01-01

    Background Expectations held by patients and health professionals may affect treatment choices and participation (by both patients and health professionals) in therapeutic interventions in contemporary patient-centered healthcare environments. If patients in rehabilitation settings overestimate their discharge health-related quality of life, they may become despondent as their progress falls short of their expectations. On the other hand, underestimating their discharge health-related quality of life may lead to a lack of motivation to participate in therapies if they do not perceive likely benefit. There is a scarcity of empirical evidence evaluating whether patients’ expectations of future health states are accurate. The purpose of this study is to evaluate the accuracy with which older patients admitted for subacute in-hospital rehabilitation can anticipate their discharge health-related quality of life. Methods A prospective longitudinal cohort investigation of agreement between patients’ anticipated discharge health-related quality of life (as reported on the EQ-5D instrument at admission to a rehabilitation unit) and their actual self-reported health-related quality of life at the time of discharge from this unit was undertaken. The mini-mental state examination was used as an indicator of patients’ cognitive ability. Results Overall, 232(85%) patients had all assessment data completed and were included in analysis. Kappa scores ranged from 0.42-0.68 across the five EQ-5D domains and two patient cognition groups. The percentage of exact correct matches within each domain ranged from 69% to 85% across domains and cognition groups. Overall 40% of participants in each cognition group correctly anticipated all of their self-reported discharge EQ-5D domain responses. Conclusions Patients admitted for subacute in-hospital rehabilitation were able to anticipate their discharge health-related quality of life on the EQ-5D instrument with a moderate level of

  16. Accuracy of Ultrasound and Noninvasive Markers of Fibrosis to Identify Patients with Cirrhosis

    PubMed Central

    Martin, Jason; Khatri, Gaurav; Gopal, Purva; Singal, Amit G.

    2015-01-01

    Background Accurate identification of patients with cirrhosis using non-invasive markers of fibrosis is useful for esophageal varices and hepatocellular carcinoma surveillance programs. The aims of our study were to characterize the accuracy of ultrasonography, AST to platelet ratio index (APRI), and FIB-4 as non-invasive markers to identify the presence of cirrhosis. Methods We conducted a retrospective cohort study of patients who underwent liver biopsy at a large urban safety-net institution between November 2008 and July 2011. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy using receiver operator characteristic curve analysis for the detection of cirrhosis were calculated for each non-invasive marker. Results Liver biopsy was performed in 388 patients, of whom 93 (24.0%) had cirrhosis. C-statistics for APRI and FIB-4 predicting the presence of cirrhosis were 0.68 (95%CI 0.63 – 0.74) and 0.73 (95%CI 0.68 – 0.78), respectively. The c-statistic for a nodular appearance on ultrasound was 0.78 (95%CI 0.72-0.83). The PPV of a shrunken nodular-appearing liver was 64.8%; however, PPV was significantly higher in the subset with a cirrhotic-appearing liver and signs of portal hypertension (PPV 83.6%, p=0.01) as well as in the subset with a non-invasive fibrosis marker also suggesting cirrhosis (PPV 77.8%, p<0.001). Conclusion Serum and imaging non-invasive markers of fibrosis may have insufficient accuracy when used in isolation; however, a combination of markers may allow sufficient accuracy to systematically identify patients with cirrhosis. PMID:25586089

  17. Identifying Elements of Patient-Centered Care in Underserved Populations: A Qualitative Study of Patient Perspectives

    PubMed Central

    Raja, Sheela; Hasnain, Memoona; Vadakumchery, Tracy; Hamad, Judy; Shah, Raveena; Hoersch, Michelle

    2015-01-01

    Patient-centered care is an important goal in the delivery of healthcare. However, many patients do not engage in preventive medical care. In this pilot study, we conducted twenty in depth, semi-structured qualitative interviews at the University of Illinois at Chicago Health Sciences campus in a four month time frame. Many patients were underserved and underinsured, and we wanted to understand their experiences in the healthcare system. Using content analysis, several themes emerged from the interview data. Participants discussed the need for empathy and rapport with their providers. They identified provider behaviors that fostered a positive clinical relationship, including step-by step explanations of procedures, attention to body language and clinic atmosphere, and appropriate time management. Participants identified cost as the most common barrier to engaging in preventive care and discussed children and social support as motivating factors. A long-term relationship with a provider was an important motivator for preventive care, suggesting that the therapeutic alliance was essential to many patients. Conversely, many participants discussed a sense of dehumanization in the healthcare system, reporting that their life circumstances were overlooked, or that they were judged based on insurance status or ethnicity. We discuss implications for provider training and healthcare delivery, including the importance of patient-centered medical homes. PMID:25993110

  18. Mirror Movements Identified in Patients with Moebius Syndrome

    PubMed Central

    Webb, Bryn D.; Frempong, Tamiesha; Naidich, Thomas P.; Gaspar, Harald; Jabs, Ethylin Wang; Rucker, Janet C.

    2014-01-01

    Background Moebius syndrome is a rare disorder with minimum clinical criteria of congenital facial weakness in association with impairment in abduction of one or both eyes. Mirror movements are not known to be associated with Moebius syndrome. Case Report We present three patients who meet minimum criteria for a diagnosis of Moebius syndrome and who also display mirror movements. Discussion This case series suggests that Moebius syndrome may be associated with mirror movements. Further investigation to delineate the genetic etiologies of Moebius syndrome is ongoing. Patients with Moebius syndrome and mirror movements may represent a specific subclass of this disorder. PMID:25120946

  19. Identifying patients at risk for recurrent or advanced BCC.

    PubMed

    Hamid, Omid; Goldenberg, Gary

    2013-11-01

    Basal cell carcinoma (BCC) is a common skin cancer and its incidence is on the rise worldwide. Clinical presentation and histologic examination are used for diagnosis and to stratify BCCs as either low- or high-risk for recurrence or development of advanced disease. A number of surgical and nonsurgical options are available for BCC. BCC is most often managed with a surgical approach, but not all tumors and patients are suitable for surgery. Vismodegib is a recently approved first-in-class hedgehog pathway inhibitor that has expanded options for patients who have locally advanced or metastatic BCC.

  20. TAVI or No TAVI: identifying patients unlikely to benefit from transcatheter aortic valve implantation.

    PubMed

    Puri, Rishi; Iung, Bernard; Cohen, David J; Rodés-Cabau, Josep

    2016-07-21

    Transcatheter aortic valve implantation (TAVI) has spawned the evolution of novel catheter-based therapies for a variety of cardiovascular conditions. Newer device iterations are delivering lower peri- and early post-procedural complication rates in patients with aortic stenosis, who were otherwise deemed too high risk for conventional surgical valve replacement. Yet beyond the post-procedural period, a considerable portion of current TAVI recipients fail to derive a benefit from TAVI, either dying or displaying a lack of clinical and functional improvement. Considerable interest now lies in better identifying factors likely to predict futility post-TAVI. Implicit in this are the critical roles of frailty, disability, and a multimorbidity patient assessment. In this review, we outline the roles that a variety of medical comorbidities play in determining futile post-TAVI outcomes, including the critical role of frailty underlying the identification of patients unlikely to benefit from TAVI. We discuss various TAVI risk scores, and further propose that by combining such scores along with frailty parameters and the presence of specific organ failure, a more accurate and holistic assessment of potential TAVI-related futility could be achieved.

  1. Is the new GFR equation using inulin clearance a more accurate method for Asian patients?

    PubMed

    Kim, Beom Seok; Lee, Yong Kyu; Choi, Hoon Young; Choi, Seung Ok; Shin, Sug Kyun; Ha, Sung Kyu; Lee, Kang Wook; Kim, Yang Wook; Kim, Yong Lim; Yasuda, Yoshinari; Imai, Enyu; Horio, Masaru; Tomino, Yasuhiko; Matsuo, Seiichi; Lee, Ho Yung

    2015-12-01

    Recently, a new glomerular filtration rate (GFR) equation for the Japanese population was proposed using measured inulin clearance. To expand its applicability to other Asian populations, we performed a comparative study in the Korean population. Inulin clearance was measured in 166 patients from seven participating medical centers in Korea. Patient's sera and urine were collected, and baseline clinical characteristics were measured to provide an estimated GFR (eGFR) by the Japanese GFR equation using inulin clearance (Japanese-GFR equation), the Modification of Diet in Renal Disease (MDRD) study equation, and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation. We compared the results to determine which equation best estimated the measured GFR (mGFR). Accuracy (95% CI) within 30% of mGFR by the Japanese-GFR equation, the CKD-EPI equation and the MDRD study equation were 66 (58 - 72), 51 (43 - 58), and 55 (47 - 62)%, respectively. Bias (mGFR minus eGFR) were 3.4 ± 22.4, -12.0 ± 22.1, and -9.7 ± 23.8 mL/min/1.73 m2, respectively. The accuracy of the Japanese-GFR equation was significantly better than MDRD study equation in subjects with mGFR < 60 mL/min/1.73 m2 and in total subjects. The bias of the Japanese-GFR equation was significantly smaller compared with other two equations in total subjects. The Japanese-GFR equation has a higher accuracy with less bias than the other equations in estimating GFR in Korean populations. Further studies are required to determine if the current Japanese-GFR equation could represent the standard eGFR for other Asian populations.

  2. Identifying the patient in George W Lambert's Chesham Street.

    PubMed

    Hammerschlag, Keren Rosa

    2013-06-01

    This paper takes as its focus one of the Edwardian period's most dramatic and little-understood paintings of a medical examination: George Washington Lambert's Chesham Street (1910). The painting shows an upper-class male patient lifting his shirt to reveal a muscular torso for examination by the doctor in the scene and the viewers outside it. The subject of a medical examination, I argue, legitimised the scrutiny of exposed male flesh and offered an opportunity for sensual pleasure between men. By way of a comparison with other portraits of the artist from around the same period, I interpret Chesham Street as a patient self-portrait, which reveals the artist's dual personalities of bohemian artist and Australian boxer: two personae that did not combine seamlessly, as revealed by the composite nature of the patient in Chesham Street. From a discussion of the artist as patient, I move to an analysis of other self-portraits by Lambert in which the artist is shown flexing his muscles, especially in the context of his passion for boxing. I consider how these portraits serve as complex inscriptions of illness and health and how this relates to the experience of living and working as an Australian expatriate artist in London in the early twentieth century.

  3. Identifying the patient in George W Lambert's Chesham Street

    PubMed Central

    Hammerschlag, Keren Rosa

    2013-01-01

    This paper takes as its focus one of the Edwardian period's most dramatic and little-understood paintings of a medical examination: George Washington Lambert's Chesham Street (1910). The painting shows an upper-class male patient lifting his shirt to reveal a muscular torso for examination by the doctor in the scene and the viewers outside it. The subject of a medical examination, I argue, legitimised the scrutiny of exposed male flesh and offered an opportunity for sensual pleasure between men. By way of a comparison with other portraits of the artist from around the same period, I interpret Chesham Street as a patient self-portrait, which reveals the artist's dual personalities of bohemian artist and Australian boxer: two personae that did not combine seamlessly, as revealed by the composite nature of the patient in Chesham Street. From a discussion of the artist as patient, I move to an analysis of other self-portraits by Lambert in which the artist is shown flexing his muscles, especially in the context of his passion for boxing. I consider how these portraits serve as complex inscriptions of illness and health and how this relates to the experience of living and working as an Australian expatriate artist in London in the early twentieth century. PMID:23349514

  4. Whole Exome Sequencing Identifies Atypical Welander Distal Myopathy in Patient

    PubMed Central

    Blackburn, Patrick; Jackson, Jessica; Harris, Kimberly; Selcen, Duygu; Dimberg, Elliot; Atwal, Paldeep

    2017-01-01

    Abstract Welander distal myopathy is a rare autosomal dominant disorder characterized by muscle weakness in the hands and feet. Exome sequencing of affected families discovered a segregating p.Glu384Lys pathogenic variant in TIA-1 as the main genetic cause of Welander distal myopathy. TIA-1 encodes an RNA-binding protein which serves as a key component of stress granules. This protein also regulates splicing and translation of mRNA. Our patient developed progressive weakness in his hands and feet during his late 40s that was misdiagnosed as a neuropathy that caused muscle atrophy. Follow-up genetic testing revealed a p.Glu384Lys pathogenic variant in TIA-1, and he was then diagnosed with Welander distal myopathy. Our case report underlines the importance of electrodiagnostic and genetic testing of patients. PMID:28221306

  5. Identifying predictors of hospice eligibility in patients with Parkinson disease.

    PubMed

    Goy, Elizabeth R; Bohlig, Amanda; Carter, Julie; Ganzini, Linda

    2015-02-01

    This study aims to improve recognition of hospice eligibility for patients with Parkinson disease (PD) by ascertaining which variables have a higher probability of occurring uniquely in 6 to 12 months before death when compared to 18 to 24 months before death. Participants were 339 patients who died who were diagnosed with PD or Parkinsonism and treated with dopaminergic prescriptions for at least 3 years in northwestern US Veterans Affairs medical centers. A range of indicators were compared across 3 time periods (30-36 months, 24-18 months, and 12-6 months before death) using within-subjects repeated measures design. Results indicate that body mass index less than 18, alone or combined with a shift in prescribing (when benefits of dopaminergic medications no longer outweigh their risk of side effects), may signal appropriate timing for hospice referral.

  6. Hypertriglyceridemia: the importance of identifying patients at risk.

    PubMed

    Kushner, Pamela A; Cobble, Michael E

    2016-11-01

    This review aims to explain risk factors, consequences, and management strategies recommended for patients with hypertriglyceridemia. A search of PubMed was performed: 'Hypertriglyceridemia'[Majr], limited to English-language and published in the 5 years up to April 2016. Abstracts of the 680 results were screened for inclusion. Reference lists of publications included were also screened for inclusion. Approximately 25% of the United States population has elevated (≥150 mg/dL) triglycerides (TG) putting them at an increased risk of cardiovascular disease, non-alcoholic fatty liver disease, and pancreatitis. Risk factors for hypertriglyceridemia include genetics, lifestyle and diet, renal disease, endocrine disorders, and certain medications. Guidelines recommend that all patients with hypertriglyceridemia are advised on lifestyle modification to reduce TG to <150 mg/dL; a reduction in body weight of 5-10% can reduce TG by approximately 20%. For patients with TG <400 mg/dL, the primary goal is to reduce low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol, with most guidelines recommending statin therapy. When TG is ≥500 mg/dL the primary goal is to reduce TG levels to lower the risk of pancreatitis. Statin therapy (if LDL-C is elevated) in combination with a fibrate, or long-chain omega-3 fatty acid may be required. The Food and Drug Administration withdrew approval for niacin and some fibrates in combination with statins in April 2016 citing unfavorable benefit-risk profiles. With the increasing incidence of associated conditions (e.g. obesity, metabolic syndrome, and type 2 diabetes mellitus), it is likely that primary care physicians will encounter more patients with hypertriglyceridemia.

  7. Voxel-based registration of simulated and real patient CBCT data for accurate dental implant pose estimation

    NASA Astrophysics Data System (ADS)

    Moreira, António H. J.; Queirós, Sandro; Morais, Pedro; Rodrigues, Nuno F.; Correia, André Ricardo; Fernandes, Valter; Pinho, A. C. M.; Fonseca, Jaime C.; Vilaça, João. L.

    2015-03-01

    The success of dental implant-supported prosthesis is directly linked to the accuracy obtained during implant's pose estimation (position and orientation). Although traditional impression techniques and recent digital acquisition methods are acceptably accurate, a simultaneously fast, accurate and operator-independent methodology is still lacking. Hereto, an image-based framework is proposed to estimate the patient-specific implant's pose using cone-beam computed tomography (CBCT) and prior knowledge of implanted model. The pose estimation is accomplished in a threestep approach: (1) a region-of-interest is extracted from the CBCT data using 2 operator-defined points at the implant's main axis; (2) a simulated CBCT volume of the known implanted model is generated through Feldkamp-Davis-Kress reconstruction and coarsely aligned to the defined axis; and (3) a voxel-based rigid registration is performed to optimally align both patient and simulated CBCT data, extracting the implant's pose from the optimal transformation. Three experiments were performed to evaluate the framework: (1) an in silico study using 48 implants distributed through 12 tridimensional synthetic mandibular models; (2) an in vitro study using an artificial mandible with 2 dental implants acquired with an i-CAT system; and (3) two clinical case studies. The results shown positional errors of 67+/-34μm and 108μm, and angular misfits of 0.15+/-0.08° and 1.4°, for experiment 1 and 2, respectively. Moreover, in experiment 3, visual assessment of clinical data results shown a coherent alignment of the reference implant. Overall, a novel image-based framework for implants' pose estimation from CBCT data was proposed, showing accurate results in agreement with dental prosthesis modelling requirements.

  8. Identifying and treating pregnant patients at risk from alcohol.

    PubMed Central

    Rosett, H. L.; Weiner, L.

    1981-01-01

    Heavy alcohol consumption during pregnancy has been associated with retardation of fetal growth and abnormal fetal development. Pregnant women whose offspring are at risk because of alcohol abuse can be identified and counselled by health professional providing prenatal care. Offspring born to women who had been drinking heavily and subsequently abstained from or reduced their intake of alcohol before the third trimester demonstrated improvements in growth and in regulation of sleep-awake states. The existing health care delivery system can be modified in a cost-effective manner to treat pregnant women who are problem drinkers. Physicians' attitudes and behaviour are critical for the success of this strategy. PMID:7272865

  9. Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians

    PubMed Central

    Oliva, Esther N.; Nobile, Francesco; Alimena, Giuliana; Ronco, Francesca; Specchia, Giorgina; Impera, Stefana; Breccia, Massimo; Vincelli, Iolanda; Carmosino, Ida; Guglielmo, Patrizia; Pastore, Domenico; Alati, Caterina; Latagliata, Roberto

    2011-01-01

    Background The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia. Design and Methods From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E). Results Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46–70; median EORTC global score 50, interquartile range 41–66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients’ perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores. Conclusions Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions. PMID:21330327

  10. Identifying patients with chronic widespread pain in primary care

    PubMed Central

    Mansfield, Kathryn E.; Sim, Julius; Croft, Peter; Jordan, Kelvin P.

    2016-01-01

    Abstract Chronic widespread pain (CWP) is common in the general population. It is unclear how people reporting this problem present in primary care; they may regularly consult for regional pains without being recognized as having a generalized condition. Our objectives were to determine the prevalence of people consulting in primary care for musculoskeletal conditions in different body regions on different occasions (recurrent regional pain consultation), the proportion with diagnosed generalized pain and survey-reported widespread pain, and if they have features characteristic of CWP. Phase 1 used electronic records from 12 general practices in North Staffordshire (Consultations in Primary Care Archive) from 2005 to 2009. Phase 2 used linked self-reported health and primary health care data from 8286 people aged >50 years in 8 general practices (North Staffordshire Osteoarthritis Project) between 2002 and 2005. In Phase 1, 11% of registered patients fulfilled criteria for recurrent regional pain consultation. Three-quarters had no recorded CWP-related generalized pain condition (eg, fibromyalgia). In Phase 2, 53% of recurrent regional pain consulters had survey-reported widespread pain and 88% had consulted for somatic symptoms. Self-reported general health was worse in recurrent regional pain consulters than in single-region consulters and poorest in those who also reported persistent widespread pain. Recurrent regional pain consulters are a heterogeneous group of frequent consulters sharing features with CWP (eg, somatic symptoms) but including those less severely affected. They lie on the spectrum of polysymptomatic distress characteristic of CWP and represent a group whose needs may be better met by earlier diagnosis of multisite pain. PMID:27749607

  11. 42 CFR 484.11 - Condition of participation: Release of patient identifiable OASIS information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... identifiable OASIS information. 484.11 Section 484.11 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Administration § 484.11 Condition of participation: Release of patient identifiable OASIS information. The HHA... confidentiality of all patient identifiable information contained in the clinical record, including OASIS...

  12. 42 CFR 484.11 - Condition of participation: Release of patient identifiable OASIS information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... identifiable OASIS information. 484.11 Section 484.11 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Administration § 484.11 Condition of participation: Release of patient identifiable OASIS information. The HHA... confidentiality of all patient identifiable information contained in the clinical record, including OASIS...

  13. 42 CFR 484.11 - Condition of participation: Release of patient identifiable OASIS information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... identifiable OASIS information. 484.11 Section 484.11 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Administration § 484.11 Condition of participation: Release of patient identifiable OASIS information. The HHA... confidentiality of all patient identifiable information contained in the clinical record, including OASIS...

  14. 42 CFR 484.11 - Condition of participation: Release of patient identifiable OASIS information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... identifiable OASIS information. 484.11 Section 484.11 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Administration § 484.11 Condition of participation: Release of patient identifiable OASIS information. The HHA... confidentiality of all patient identifiable information contained in the clinical record, including OASIS...

  15. 42 CFR 484.11 - Condition of participation: Release of patient identifiable OASIS information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... identifiable OASIS information. 484.11 Section 484.11 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Administration § 484.11 Condition of participation: Release of patient identifiable OASIS information. The HHA... confidentiality of all patient identifiable information contained in the clinical record, including OASIS...

  16. Evaluation of ICD-10 algorithms to identify hypopituitary patients in the Danish National Patient Registry

    PubMed Central

    Berglund, Agnethe; Olsen, Morten; Andersen, Marianne; Nielsen, Eigil Husted; Feldt-Rasmussen, Ulla; Kistorp, Caroline; Gravholt, Claus Højbjerg; Stochhholm, Kirstine

    2017-01-01

    Objective Routinely collected health data may be valuable sources for conducting research. This study aimed to evaluate the validity of algorithms detecting hypopituitary patients in the Danish National Patient Registry (DNPR) using medical records as reference standard. Study design and setting Patients with International Classification of Diseases (10th edition [ICD-10]) diagnoses of hypopituitarism, or other diagnoses of pituitary disorders assumed to be associated with an increased risk of hypopituitarism, recorded in the DNPR during 2000–2012 were identified. Medical records were reviewed to confirm or disprove hypopituitarism. Results Hypopituitarism was confirmed in 911 patients. In a candidate population of 1,661, this yielded an overall positive predictive value (PPV) of 54.8% (95% confidence interval [CI]: 52.4–57.3). Using algorithms searching for patients recorded at least one, three or five times with a diagnosis of hypopituitarism (E23.0x) and/or at least once with a diagnosis of postprocedural hypopituitarism (E89.3x), PPVs gradually increased from 73.3% (95% CI: 70.6–75.8) to 83.3% (95% CI: 80.7–85.7). Completeness for the same algorithms, however, decreased from 90.8% (95% CI: 88.7–92.6) to 82.9% (95% CI: 80.3–85.3) respectively. Including data of hormone replacement in the same algorithms PPVs increased from 73.2% (95% CI: 70.6–75.7) to 82.6% (95% CI: 80.1–84.9) and completeness decreased from 94.3% (95% CI: 92.6–95.7) to 89.7% (95% CI: 87.5–91.6) with increasing records of E23.0x. Conclusion The DNPR is a valuable data source to identify hypopituitary patients using a search criteria of at least five records of E23.0x and/or at least one record of E89.3x. Completeness is increased when including hormone replacement data in the algorithm. The consequences of misclassification must, however, always be considered. PMID:28223847

  17. A methodological approach to identify cheap and accurate indicators for biodiversity assessment: application to grazing management and two grassland bird species.

    PubMed

    Tichit, M; Barbottin, A; Makowski, D

    2010-06-01

    In response to environmental threats, numerous indicators have been developed to assess the impact of livestock farming systems on the environment. Some of them, notably those based on management practices have been reported to have low accuracy. This paper reports the results of a study aimed at assessing whether accuracy can be increased at a reasonable cost by mixing individual indicators into models. We focused on proxy indicators representing an alternative to the direct impact measurement on two grassland bird species, the lapwing Vanellus vanellus and the redshank Tringa totanus. Models were developed using stepwise selection procedures or Bayesian model averaging (BMA). Sensitivity, specificity, and probability of correctly ranking fields (area under the curve, AUC) were estimated for each individual indicator or model from observational data measured on 252 grazed plots during 2 years. The cost of implementation of each model was computed as a function of the number and types of input variables. Among all management indicators, 50% had an AUC lower than or equal to 0.50 and thus were not better than a random decision. Independently of the statistical procedure, models combining management indicators were always more accurate than individual indicators for lapwings only. In redshanks, models based either on BMA or some selection procedures were non-informative. Higher accuracy could be reached, for both species, with model mixing management and habitat indicators. However, this increase in accuracy was also associated with an increase in model cost. Models derived by BMA were more expensive and slightly less accurate than those derived with selection procedures. Analysing trade-offs between accuracy and cost of indicators opens promising application perspectives as time consuming and expensive indicators are likely to be of low practical utility.

  18. Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

    SciTech Connect

    Doherty, Kimberly R. Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

    2015-05-15

    Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

  19. Identifying Depression in South Asian Patients with End-Stage Renal Disease: Considerations for Practice

    PubMed Central

    Sharma, Shivani; Bhui, Kamaldeep; Chilcot, Joseph; Wellsted, David; Farrington, Ken

    2011-01-01

    Depression is a prevalent burden for patients with end-stage renal disease (ESRD) and one that is under-recognized and consequently under-treated. Although several studies have explored the association between depression symptoms, treatment adherence and outcomes in Euro-American patient groups, quantitative and qualitative exploration of these issues in patients from different cultural and ethnic backgrounds has been lacking. This review discusses the methodological issues associated with measuring depression in patients of South Asian origin who have a 3- to 5-fold greater risk of developing ESRD. There is a need to advance research into the development of accurate screening practices for this patient group, with an emphasis on studies utilizing rigorous approaches to evaluating the use of both emic (culture-specific) and etic (universal or culture-general) screening instruments. PMID:22470400

  20. Fast and accurate method for identifying high-quality protein-interaction modules by clique merging and its application to yeast.

    PubMed

    Zhang, Chi; Liu, Song; Zhou, Yaoqi

    2006-04-01

    Molecular networks in cells are organized into functional modules, where genes in the same module interact densely with each other and participate in the same biological process. Thus, identification of modules from molecular networks is an important step toward a better understanding of how cells function through the molecular networks. Here, we propose a simple, automatic method, called MC(2), to identify functional modules by enumerating and merging cliques in the protein-interaction data from large-scale experiments. Application of MC(2) to the S. cerevisiae protein-interaction data produces 84 modules, whose sizes range from 4 to 69 genes. The majority of the discovered modules are significantly enriched with a highly specific process term (at least 4 levels below root) and a specific cellular component in Gene Ontology (GO) tree. The average fraction of genes with the most enriched GO term for all modules is 82% for specific biological processes and 78% for specific cellular components. In addition, the predicted modules are enriched with coexpressed proteins. These modules are found to be useful for annotating unknown genes and uncovering novel functions of known genes. MC(2) is efficient, and takes only about 5 min to identify modules from the current yeast gene interaction network with a typical PC (Intel Xeon 2.5 GHz CPU and 512 MB memory). The CPU time of MC(2) is affordable (12 h) even when the number of interactions is increased by a factor of 10. MC(2) and its results are publicly available on http://theory.med.buffalo.edu/MC2.

  1. Identifying Adolescent Patients at Risk for Sexually Transmitted Infections: Development of a Brief Sexual Health Screening Survey.

    PubMed

    Victor, Elizabeth C; Chung, Richard; Thompson, Robert J

    2015-08-01

    This study examined the association between survey responses to health behaviors, personality/psychosocial factors, and self-reported sexually transmitted infections (STIs) to create a brief survey to identify youth at risk for contracting STIs. Participants included 200 racially diverse 14- to 18-year-old patients from a pediatric primary care clinic. Two sexual behavior variables and one peer norm variable were used to differentiate subgroups of individuals at risk of contracting a STI based on reported history of STIs using probability (decision tree) analyses. These items, as well as sexual orientation and having ever had oral sex, were used to create a brief sexual health screening (BSHS) survey. Each point increase in total BSHS score was associated with exponential growth in the percentage of sexually active adolescents reporting STIs. Findings suggest that the BSHS could serve as a useful tool for clinicians to quickly and accurately detect sexual risk among adolescent patients.

  2. The challenge of monitoring elusive large carnivores: An accurate and cost-effective tool to identify and sex pumas (Puma concolor) from footprints

    PubMed Central

    2017-01-01

    Acquiring reliable data on large felid populations is crucial for effective conservation and management. However, large felids, typically solitary, elusive and nocturnal, are difficult to survey. Tagging and following individuals with VHF or GPS technology is the standard approach, but costs are high and these methodologies can compromise animal welfare. Such limitations can restrict the use of these techniques at population or landscape levels. In this paper we describe a robust technique to identify and sex individual pumas from footprints. We used a standardized image collection protocol to collect a reference database of 535 footprints from 35 captive pumas over 10 facilities; 19 females (300 footprints) and 16 males (235 footprints), ranging in age from 1–20 yrs. Images were processed in JMP data visualization software, generating one hundred and twenty three measurements from each footprint. Data were analyzed using a customized model based on a pairwise trail comparison using robust cross-validated discriminant analysis with a Ward’s clustering method. Classification accuracy was consistently > 90% for individuals, and for the correct classification of footprints within trails, and > 99% for sex classification. The technique has the potential to greatly augment the methods available for studying puma and other elusive felids, and is amenable to both citizen-science and opportunistic/local community data collection efforts, particularly as the data collection protocol is inexpensive and intuitive. PMID:28273159

  3. The challenge of monitoring elusive large carnivores: An accurate and cost-effective tool to identify and sex pumas (Puma concolor) from footprints.

    PubMed

    Alibhai, Sky; Jewell, Zoe; Evans, Jonah

    2017-01-01

    Acquiring reliable data on large felid populations is crucial for effective conservation and management. However, large felids, typically solitary, elusive and nocturnal, are difficult to survey. Tagging and following individuals with VHF or GPS technology is the standard approach, but costs are high and these methodologies can compromise animal welfare. Such limitations can restrict the use of these techniques at population or landscape levels. In this paper we describe a robust technique to identify and sex individual pumas from footprints. We used a standardized image collection protocol to collect a reference database of 535 footprints from 35 captive pumas over 10 facilities; 19 females (300 footprints) and 16 males (235 footprints), ranging in age from 1-20 yrs. Images were processed in JMP data visualization software, generating one hundred and twenty three measurements from each footprint. Data were analyzed using a customized model based on a pairwise trail comparison using robust cross-validated discriminant analysis with a Ward's clustering method. Classification accuracy was consistently > 90% for individuals, and for the correct classification of footprints within trails, and > 99% for sex classification. The technique has the potential to greatly augment the methods available for studying puma and other elusive felids, and is amenable to both citizen-science and opportunistic/local community data collection efforts, particularly as the data collection protocol is inexpensive and intuitive.

  4. A Comprehensive Approach to Identifying Intervention Targets for Patient-Safety Improvement in a Hospital Setting

    ERIC Educational Resources Information Center

    Cunningham, Thomas R.; Geller, E. Scott

    2012-01-01

    Despite differences in approaches to organizational problem solving, healthcare managers and organizational behavior management (OBM) practitioners share a number of practices, and connecting healthcare management with OBM may lead to improvements in patient safety. A broad needs-assessment methodology was applied to identify patient-safety…

  5. Using Learning Analytics to Identify Medical Student Misconceptions in an Online Virtual Patient Environment

    ERIC Educational Resources Information Center

    Poitras, Eric G.; Naismith, Laura M.; Doleck, Tenzin; Lajoie, Susanne P.

    2016-01-01

    This study aimed to identify misconceptions in medical student knowledge by mining user interactions in the MedU online learning environment. Data from 13000 attempts at a single virtual patient case were extracted from the MedU MySQL database. A subgroup discovery method was applied to identify patterns in learner-generated annotations and…

  6. Identifying priority actions for improving patient satisfaction with outpatient cancer care.

    PubMed

    Gesell, Sabina B; Gregory, Nancy

    2004-01-01

    In parallel to developing new cancer therapies, the healthcare community has the responsibility of creating positive treatment experiences for patients. Data from 5907 cancer outpatients treated at 23 hospitals across the United States were analyzed to identify the top priorities for service improvement in outpatient cancer treatment facilities. They included meeting patients' emotional needs, providing information to patients and family members, reducing waiting times, and providing convenience and coordinated care among physicians and other care providers.

  7. Patient safety in plastic surgery: identifying areas for quality improvement efforts.

    PubMed

    Hernandez-Boussard, Tina; McDonald, Kathryn M; Rhoads, Kim F; Curtin, Catherine M

    2015-05-01

    Improving quality of health care is a global priority. Before quality benchmarks are established, we first must understand rates of adverse events (AEs). This project assessed risk-adjusted rates of inpatient AEs for soft tissue reconstructive procedures.Patients receiving soft tissue reconstructive procedures from 2005 to 2010 were extracted from the Nationwide Inpatient Sample. Inpatient AEs were identified using patient safety indicators (PSIs), established measures developed by Agency for Healthcare Research and Quality.We identified 409,991 patients with soft tissue reconstruction and 16,635 (4.06%) had a PSI during their hospital stay. Patient safety indicators were associated with increased risk-adjusted mortality, longer length of stay, and decreased routine disposition (P < 0.01). Patient characteristics associated with a higher risk-adjusted rate per 1000 patients at risk included older age, men, nonwhite, and public payer (P < 0.05). Overall, plastic surgery patients had significantly lower risk-adjusted rate compared to other surgical inpatients for all events evaluated except for failure to rescue and postoperative hemorrhage or hematoma, which were not statistically different. Risk-adjusted rates of hematoma hemorrhage were significantly higher in patients receiving size-reduction surgery, and these rates were further accentuated when broken down by sex and payer. In general, plastic surgery patients had lower rates of in-hospital AEs than other surgical disciplines, but PSIs were not uncommon. With the establishment of national basal PSI rates in plastic surgery patients, benchmarks can be devised and target areas for quality improvement efforts identified. Further prospective studies should be designed to elucidate the drivers of AEs identified in this population.

  8. Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients

    PubMed Central

    Ferrari, Clarissa; Uher, Rudolf; Bocchio-Chiavetto, Luisella; Riva, Marco Andrea; Pariante, Carmine M.

    2016-01-01

    Background: Increased levels of inflammation have been associated with a poorer response to antidepressants in several clinical samples, but these findings have had been limited by low reproducibility of biomarker assays across laboratories, difficulty in predicting response probability on an individual basis, and unclear molecular mechanisms. Methods: Here we measured absolute mRNA values (a reliable quantitation of number of molecules) of Macrophage Migration Inhibitory Factor and interleukin-1β in a previously published sample from a randomized controlled trial comparing escitalopram vs nortriptyline (GENDEP) as well as in an independent, naturalistic replication sample. We then used linear discriminant analysis to calculate mRNA values cutoffs that best discriminated between responders and nonresponders after 12 weeks of antidepressants. As Macrophage Migration Inhibitory Factor and interleukin-1β might be involved in different pathways, we constructed a protein-protein interaction network by the Search Tool for the Retrieval of Interacting Genes/Proteins. Results: We identified cutoff values for the absolute mRNA measures that accurately predicted response probability on an individual basis, with positive predictive values and specificity for nonresponders of 100% in both samples (negative predictive value=82% to 85%, sensitivity=52% to 61%). Using network analysis, we identified different clusters of targets for these 2 cytokines, with Macrophage Migration Inhibitory Factor interacting predominantly with pathways involved in neurogenesis, neuroplasticity, and cell proliferation, and interleukin-1β interacting predominantly with pathways involved in the inflammasome complex, oxidative stress, and neurodegeneration. Conclusion: We believe that these data provide a clinically suitable approach to the personalization of antidepressant therapy: patients who have absolute mRNA values above the suggested cutoffs could be directed toward earlier access to more

  9. Partner notification and focused intervention as a means of identifying HIV-positive patients.

    PubMed

    Jordan, W C; Tolbert, L; Smith, R

    1998-09-01

    Partner notification as a means of contact tracing human immunodeficiency virus (HIV)-infected persons remains controversial. It is argued against by many gay activists, while primary public health officials and leaders in ethnic communities continue to support this as a means of identifying unknown cases. Human immunodeficiency virus-positive patients were interviewed to determine if partner notification could be a useful instrument. Based on interviews, patients at risk of infection through heterosexual contact were able to identify most of their sexual partners; the majority of these patients were women. Twenty-two of 22 women infected heterosexually were able to identify all of their sexual partners. Five of 8 heterosexual men were able to identify all of their sexual partners, but these men were infected through intravenous drug use. Six of 44 homosexual men interviewed were able to make these identifications. Two focus groups of homosexual men who were HIV-positive patients were organized; each was asked one question. Men in group B were asked if they could identify HIV-positive persons whom they suspected were not in a treatment program. Men in group A were asked if they they thought they knew HIV-positive persons still practicing unsafe sex. Thirteen of the 14 patients in group A were able to identify 30 persons they felt were still practicing unsafe sex; 17 of 30 tested HIV-positive and 9 were unaware of their status. The 14 patients in group B identified 15 persons they felt were HIV-positive; 11 were found to be HIV-positive and 8 were unaware of their status. These findings suggest that partner notification definitely has a role in heterosexual contact tracing, and focused intervention is a more cost-effective approach to early intervention.

  10. Development of administrative data algorithms to identify patients with critical limb ischemia.

    PubMed

    Bekwelem, Wobo; Bengtson, Lindsay G S; Oldenburg, Niki C; Winden, Tamara J; Keo, Hong H; Hirsch, Alan T; Duval, Sue

    2014-12-01

    Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases (n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance.

  11. An Algorithm Using Administrative Data to Identify Patient Attachment to a Family Physician

    PubMed Central

    Provost, Sylvie; Pérez, José; Pineault, Raynald; Borgès Da Silva, Roxane; Tousignant, Pierre

    2015-01-01

    Background. Commonly self-reported questions in population health surveys, such as “do you have a family physician?”, represent one of the best-known sources of information about patients' attachment to family physicians. Is it possible to find a proxy for this information in administrative data? Objective. To identify the type of patient attachment to a family physician using administrative data. Methods. Using physician fee-for-service database and patients enrolment registries (Quebec, Canada, 2008–2010), we developed a step-by-step algorithm including three dimensions of the physician-patient relationship: patient enrolment with a physician, complete annual medical examinations (CME), and concentration of visits to a physician. Results. 68.1% of users were attached to a family physician; for 34.4% of them, attachment was defined by enrolment with a physician, for 31.5%, by CME without enrolment, and, for 34.1%, by concentration of visits to a physician without enrolment or CME. Eight types of patient attachment were described. Conclusion. When compared to findings with survey data, our measure comes out as a solid conceptual framework to identify patient attachment to a family physician in administrative databases. This measure could be of great value for physician/patient-based cohort development and impact assessment of different types of patient attachment on health services utilization. PMID:26413320

  12. Patient Safety in Plastic Surgery: Identifying Areas for Quality Improvement Efforts

    PubMed Central

    Hernandez-Boussard, Tina; McDonald, Kathryn M.; Rhoads, Kim F.; Curtin, Catherine M.

    2016-01-01

    Summary Background Improving quality of healthcare is a global priority. Before quality benchmarks are established, we first must understand rates of adverse events. This project assessed risk-adjusted rates of inpatient adverse events for soft tissue reconstructive procedures. Methods Patients receiving soft tissue reconstructive procedures from 2005–2010 were extracted from the Nationwide Inpatient Sample. Inpatient adverse events were identified using patient safety indicators (PSI), established measures developed by Agency for Healthcare Research and Quality. Results We identified 409,991 patient with soft tissue reconstruction and 16,635 (4.06%) had a PSI during their hospital stay. PSIs were associated with increased risk-adjusted mortality, longer length of stay, and decreased routine disposition (p<.01). Patient characteristics associated with a higher risk-adjusted rate per 1,000 patients at risk (RAR) included older age, men, non-white, and public payer (p<.05). Overall, plastic surgery patients had significantly lower RAR compared to other surgical inpatients for all events evaluated except for failure to rescue and postoperative hemorrhage or hematoma, which were not statistically different. RAR of hematoma hemorrhage were significantly higher in patients receiving size-reduction surgery, and these rates were further accentuated when broken down by gender and payer. Conclusions In general, plastic surgery patients had lower rates of in-hospital adverse events than other surgical disciplines, but PSIs were not uncommon. With the establishment of national basal PSI rates in plastic surgery patients, benchmarks can be devised and target areas for quality improvement efforts identified. Further prospective studies should be designed to elucidate the drivers of adverse events identified in this population. PMID:24108144

  13. Using Active Learning to Identify Health Information Technology Related Patient Safety Events.

    PubMed

    Fong, Allan; Howe, Jessica L; Adams, Katharine T; Ratwani, Raj M

    2017-01-18

    The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports. In this paper, we apply active learning techniques to support classification of patient safety event reports as HIT-related. We evaluated different strategies and demonstrated a 30% increase in average precision of a confirmatory sampling strategy over a baseline no active learning approach after 10 learning iterations.

  14. A Novel Approach to Identifying a Neuroimaging Biomarker for Patients With Serious Mental Illness.

    PubMed

    Madan, Alok; Fowler, J Christopher; Patriquin, Michelle A; Salas, Ramiro; Baldwin, Philip R; Velasquez, Kenia M; Viswanath, Humsini; Molfese, David L; Sharp, Carla; Allen, Jon G; Hardesty, Susan; Oldham, John M; Frueh, B Christopher

    2017-02-27

    Serious mental illness (SMI) is disabling, and current interventions are ineffective for many. This exploratory study sought to demonstrate the feasibility of applying topological data analysis (TDA) to resting-state functional connectivity data obtained from a heterogeneous sample of 235 adult inpatients to identify a biomarker of treatment response. TDA identified two groups based on connectivity between the prefrontal cortex and striatal regions: patients admitted with greater functional connectivity between these regions evidenced less improvement from admission to discharge than patients with lesser connectivity between them. TDA identified a potential biomarker of an attenuated treatment response among inpatients with SMI. Insofar as the observed pattern of resting-state functional connectivity collected early during treatment is replicable, this potential biomarker may indicate the need to modify standard of care for a small, albeit meaningful, percentage of patients.

  15. Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

    PubMed

    Morrone, A; Tylee, K L; Al-Sayed, M; Brusius-Facchin, A C; Caciotti, A; Church, H J; Coll, M J; Davidson, K; Fietz, M J; Gort, L; Hegde, M; Kubaski, F; Lacerda, L; Laranjeira, F; Leistner-Segal, S; Mooney, S; Pajares, S; Pollard, L; Ribeiro, I; Wang, R Y; Miller, N

    2014-06-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

  16. [Patients forgoing health care for economic reasons: how to identify this in a primary care setting?].

    PubMed

    Bodenmann, Patrick; Wolff, Hans; Bischoff, Thomas; Herzig, Lilli; Warin, Philippe; Chatelard, Sophia; Burnand, Bernard; Vaucher, Paul; Favrat, Bernard; Panese Francesco; Jackson, Yves L; Vu, Francis; Guessous, Idris

    2014-11-26

    Although the performance of the Swiss health system is high, one out of ten patients in general practitioner's (GP) office declares having foregone care in the previous twelve months for economic reasons. Reasons for foregoing care are several and include a lack of knowledge of existing social aids in getting health insurance, unavailability of GPs and long waiting lists for various types of care. Although long term knowledge of patients or a psychosocial history of deprivation or poverty may help identify individuals at risk of foregoing care, many may remain undetected. We propose then a few instruments to help GPs to identify, in a simple and structured approach, patients at risk of forgoing care for economic reasons; these patients are frequently deprived and sometimes poor.

  17. Clinical Workflow Observations to Identify Opportunities for Nurse, Physicians and Patients to Share a Patient-centered Plan of Care.

    PubMed

    Collins, Sarah A; Gazarian, Priscilla; Stade, Diana; McNally, Kelly; Morrison, Conny; Ohashi, Kumiko; Lehmann, Lisa; Dalal, Anuj; Bates, David W; Dykes, Patricia C

    2014-01-01

    Patient- and Family-Centered Care (PFCC) is essential for high quality care in the critical and acute-specialty care hospital setting. Effective PFCC requires clinicians to form an integrated interprofessional team to collaboratively engage with the patient/family and contribute to a shared patient-centered plan of care. We conducted observations on a critical care and specialty unit to understand the plan of care activities and workflow documentation requirements for nurses and physicians to inform the development of a shared patient-centered plan of care to support patient engagement. We identified siloed plan of care documentation, with workflow opportunities to converge the nurses plan of care with the physician planned To-do lists and quality and safety checklists. Integration of nurses and physicians plan of care activities into a shared plan of care is a feasible and valuable step toward interprofessional teams that effectively engage patients in plan of care activities.

  18. [Clinical nurses' attitudes toward the abilities to identify and help alcoholic patients].

    PubMed

    Vargas, Divane

    2010-01-01

    This descriptive-exploratory study aimed to investigate nurses' attitudes towards the abilities to identify and to help alcoholic persons. Data were collected through an attitude scale in a sample of 171 nurses at a university hospital in São Paulo State. The results evidenced that the nurses feel skilled to help these patients achieve recovery, demonstrating positive attitudes; however, conflict was identified in attitudes towards the alcoholic patients' desire, revealing the influence of the moral model to explain alcoholism. It is concluded that overcoming these conflicts in attitudes will only be possible when they are acknowledged by the nurses and when this problem receives greater attention during professional education.

  19. Clinically Relevant Variants Identified in Thoracic Aortic Aneurysm Patients by Research Exome Sequencing

    PubMed Central

    Schubert, Jeffrey A.; Landis, Benjamin J.; Shikany, Amy R.; Hinton, Robert B.; Ware, Stephanie M.

    2016-01-01

    Thoracic aortic aneurysm (TAA) is a genetically heterogeneous disease involving subclinical and progressive dilation of the thoracic aorta, which can lead to life-threatening complications such as dissection or rupture. Genetic testing is important for risk stratification and identification of at risk family members, and clinically available genetic testing panels have been expanding rapidly. However, when past testing results are normal, there is little evidence to guide decision-making about the indications and timing to pursue additional clinical genetic testing. Results from research based genetic testing can help inform this process. Here we present 10 TAA patients who have a family history of disease and who enrolled in research-based exome testing. Nine of these ten patients had previous clinical genetic testing that did not identify the cause of disease. We sought to determine the number of rare variants in 23 known TAA associated genes identified by research-based exome testing. In total, we found 10 rare variants in six patients. Likely pathogenic variants included a TGFB2 variant in one patient and a SMAD3 variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in MYLK and MFAP5, which were identified in a third patient. In total, clinically reportable rare variants were found in 6/10 (60%) patients, with at least 2/10 (20%) patients having likely pathogenic variants identified. These data indicate that consideration of re-testing is important in TAA patients with previous negative or inconclusive results. PMID:26854089

  20. Using routine inpatient data to identify patients at risk of hospital readmission

    PubMed Central

    Howell, Stuart; Coory, Michael; Martin, Jennifer; Duckett, Stephen

    2009-01-01

    Background A relatively small percentage of patients with chronic medical conditions account for a much larger percentage of inpatient costs. There is some evidence that case-management can improve health and quality-of-life and reduce the number of times these patients are readmitted. To assess whether a statistical algorithm, based on routine inpatient data, can be used to identify patients at risk of readmission and who would therefore benefit from case-management. Methods Queensland database study of public-hospital patients, who had at least one emergency admission for a chronic medical condition (e.g., congestive heart failure, chronic obstructive pulmonary disease, diabetes or dementia) during 2005/2006. Multivariate logistic regression was used to develop an algorithm to predict readmission within 12 months. The performance of the algorithm was tested against recorded readmissions using sensitivity, specificity, and Likelihood Ratios (positive and negative). Results Several factors were identified that predicted readmission (i.e., age, co-morbidities, economic disadvantage, number of previous admissions). The discriminatory power of the model was modest as determined by area under the receiver operating characteristic (ROC) curve (c = 0.65). At a risk score threshold of 50, the algorithm identified only 44.7% (95% CI: 42.5%, 46.9%) of patients admitted with a reference condition who had an admission in the next 12 months; 37.5% (95% CI: 35.0%, 40.0%) of patients were flagged incorrectly (they did not have a subsequent admission). Conclusion A statistical algorithm based on Queensland hospital inpatient data, performed only moderately in identifying patients at risk of readmission. The main problem is that there are too many false negatives, which means that many patients who might benefit would not be offered case-management. PMID:19505342

  1. The Effect of Physician Solicitation Approaches on Ability to Identify Patient Concerns

    PubMed Central

    Dyche, Lawrence; Swiderski, Deborah

    2005-01-01

    CONTEXT Studies showing that physicians often interrupt the patient's opening statement assume that this compromises data collection. OBJECTIVE To explore the association between such interruptions and physician accuracy in identifying patient concerns. DESIGN This study replicates the Beckman-Frankel methodology and adds exit interviews to assess physician understanding. The authors audiotaped a convenience sample of 70 encounters and surveyed both parties following the visit. SETTING A community-based ambulatory clinic. PARTICIPANTS Internal medicine residents (77%) and attending physicians and their adult, English-speaking patients who were primarily low income and ethnic minority. OUTCOME MEASURE The Index of Understanding measures patient-physician problem list concordance. It is the percentage of patient problems, obtained on exit, that the physician correctly identifies. RESULTS In 26% of the visits, patients were allowed to complete their agenda without interruption; in 37% the physicians interrupted; and in 37% no inquiry about agenda was made in the first 5 minutes. Neither physician experience nor their assessment of time pressure or medical difficulty was associated with these rates. Exit interviews showed no significant difference in Index of Understanding between those involving completion of agenda (84.6%) and those involving patient interruption (82.4%) (P=.83). But when the physician did not solicit an agenda, the concordance was 59.2%, significantly lower than either the completion (P=.014) or the interruption group (P=.013). CONCLUSION Interruption as defined by Beckman-Frankel does not curtail ability to identify patient concerns, but failure to ask for the patient's agenda associates with a 24% reduction in physician understanding. PMID:15836531

  2. Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients.

    PubMed

    Abd Al Samid, May; Chaudhary, Belal; Khaled, Yazan S; Ammori, Basil J; Elkord, Eyad

    2016-03-22

    Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3-Helios+ and activated FoxP3+/-Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3-LAP+ Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+ activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP-/+LAP+ CD4+ T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.

  3. Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

    PubMed Central

    Raz, Noa; Hallak, Michal; Ben-Hur, Tamir; Levin, Netta

    2014-01-01

    In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients. In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS. PMID

  4. A new screening pathway for identifying asymptomatic patients using dental panoramic radiographs

    NASA Astrophysics Data System (ADS)

    Hayashi, Tatsuro; Matsumoto, Takuya; Sawagashira, Tsuyoshi; Tagami, Motoki; Katsumata, Akitoshi; Hayashi, Yoshinori; Muramatsu, Chisako; Zhou, Xiangrong; Iida, Yukihiro; Matsuoka, Masato; Katagi, Kiyoji; Fujita, Hiroshi

    2012-03-01

    To identify asymptomatic patients is the challenging task and the essential first step in diagnosis. Findings of dental panoramic radiographs include not only dental conditions but also radiographic signs that are suggestive of possible systemic diseases such as osteoporosis, arteriosclerosis, and maxillary sinusitis. Detection of such signs on panoramic radiographs has a potential to provide supplemental benefits for patients. However, it is not easy for general dental practitioners to pay careful attention to such signs. We addressed the development of a computer-aided detection (CAD) system that detects radiographic signs of pathology on panoramic images, and the design of the framework of new screening pathway by cooperation of dentists and our CAD system. The performance evaluation of our CAD system showed the sensitivity and specificity in the identification of osteoporotic patients were 92.6 % and 100 %, respectively, and those of the maxillary sinus abnormality were 89.6 % and 73.6 %, respectively. The detection rate of carotid artery calcifications that suggests the need for further medical evaluation was approximately 93.6 % with 4.4 false-positives per image. To validate the utility of the new screening pathway, preliminary clinical trials by using our CAD system were conducted. To date, 223 panoramic images were processed and 4 asymptomatic patients with suspected osteoporosis, 7 asymptomatic patients with suspected calcifications, and 40 asymptomatic patients with suspected maxillary sinusitis were detected in our initial trial. It was suggested that our new screening pathway could be useful to identify asymptomatic patients with systemic diseases.

  5. Towards a classification model to identify hospice candidates in terminally ill patients.

    PubMed

    Gil-Herrera, Eleazar; Yalcin, Ali; Tsalatsanis, Athanasios; Barnes, Laura E; Djulbegovic, Benjamin

    2012-01-01

    This paper presents a Rough Set Theory (RST) based classification model to identify hospice candidates within a group of terminally ill patients. Hospice care considerations are particularly valuable for terminally ill patients since they enable patients and their families to initiate end-of-life discussions and choose the most desired management strategy for the remainder of their lives. Unlike traditional data mining methodologies, our approach seeks to identify subgroups of patients possessing common characteristics that distinguish them from other subgroups in the dataset. Thus, heterogeneity in the data set is captured before the classification model is built. Object related reducts are used to obtain the minimum set of attributes that describe each subgroup existing in the dataset. As a result, a collection of decision rules is derived for classifying new patients based on the subgroup to which they belong. Results show improvements in the classification accuracy compared to a traditional RST methodology, in which patient diversity is not considered. We envision our work as a part of a comprehensive decision support system designed to facilitate end-of-life care decisions. Retrospective data from 9105 patients is used to demonstrate the design and implementation details of the classification model.

  6. A Bayesian Credible Subgroups Approach to Identifying Patient Subgroups with Positive Treatment Effects

    PubMed Central

    Tang, Qi; Offen, Walter W.; Carlin, Bradley P.

    2016-01-01

    Summary Many new experimental treatments benefit only a subset of the population. Identifying the baseline covariate profiles of patients who benefit from such a treatment, rather than determining whether or not the treatment has a population-level effect, can substantially lessen the risk in undertaking a clinical trial and expose fewer patients to treatments that do not benefit them. The standard analyses for identifying patient subgroups that benefit from an experimental treatment either do not account for multiplicity, or focus on testing for the presence of treatment-covariate interactions rather than the resulting individualized treatment effects. We propose a Bayesian credible subgroups method to identify two bounding subgroups for the benefiting subgroup: one for which it is likely that all members simultaneously have a treatment effect exceeding a specified threshold, and another for which it is likely that no members do. We examine frequentist properties of the credible subgroups method via simulations and illustrate the approach using data from an Alzheimer's disease treatment trial. We conclude with a discussion of the advantages and limitations of this approach to identifying patients for whom the treatment is beneficial. PMID:27159131

  7. Identifying an Inciting Antigen Is Associated With Improved Survival in Patients With Chronic Hypersensitivity Pneumonitis

    PubMed Central

    Swigris, Jeffrey J.; Forssén, Anna V.; Tourin, Olga; Solomon, Joshua J.; Huie, Tristan J.; Olson, Amy L.; Brown, Kevin K.

    2013-01-01

    Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP. Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis. Results: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047). Conclusions: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival. PMID:23828161

  8. Extensive portal venous gas in a post-operative patient with no identifiable cause

    PubMed Central

    Hussein, Adam; Makhija, Rohit

    2015-01-01

    Gas within the portal venous system is often considered a pre-morbid radiological sign. We present a case of extensive portal venous gas (PVG) identified in a patient 6 days following emergency Hartmann's procedure for large bowel obstruction. The patient underwent re-laparotomy on the basis of these radiological findings, but no clear cause was identified. She went on to have an uneventful recovery. Of interest is the discrepancy between the extent of PVG on the preoperative imaging in comparison with the lack of positive findings on direct visualization at laparotomy. We discuss the causes of PVG, its clinical significance, strategies for its management and, in particular, whether surgical management is always indicated in such patients. PMID:26515340

  9. Case-based reasoning using electronic health records efficiently identifies eligible patients for clinical trials

    PubMed Central

    Miotto, Riccardo

    2015-01-01

    Objective To develop a cost-effective, case-based reasoning framework for clinical research eligibility screening by only reusing the electronic health records (EHRs) of minimal enrolled participants to represent the target patient for each trial under consideration. Materials and Methods The EHR data—specifically diagnosis, medications, laboratory results, and clinical notes—of known clinical trial participants were aggregated to profile the “target patient” for a trial, which was used to discover new eligible patients for that trial. The EHR data of unseen patients were matched to this “target patient” to determine their relevance to the trial; the higher the relevance, the more likely the patient was eligible. Relevance scores were a weighted linear combination of cosine similarities computed over individual EHR data types. For evaluation, we identified 262 participants of 13 diversified clinical trials conducted at Columbia University as our gold standard. We ran a 2-fold cross validation with half of the participants used for training and the other half used for testing along with other 30 000 patients selected at random from our clinical database. We performed binary classification and ranking experiments. Results The overall area under the ROC curve for classification was 0.95, enabling the highlight of eligible patients with good precision. Ranking showed satisfactory results especially at the top of the recommended list, with each trial having at least one eligible patient in the top five positions. Conclusions This relevance-based method can potentially be used to identify eligible patients for clinical trials by processing patient EHR data alone without parsing free-text eligibility criteria, and shows promise of efficient “case-based reasoning” modeled only on minimal trial participants. PMID:25769682

  10. Preoperative biliary drainage in Perihilar Cholangiocarcinoma: Identifying patients who require percutaneous drainage after failed endoscopic drainage

    PubMed Central

    Wiggers, Jimme K; Koerkamp, Bas Groot; Coelen, Robert J; Rauws, Erik A; Schattner, Mark A; Nio, C Yung; Brown, Karen T; Gonen, Mithat; van Dieren, Susan; van Lienden, Krijn P; Allen, Peter J; Besselink, Marc GH; Busch, Olivier RC; D’Angelica, Michael I; DeMatteo, Robert P; Gouma, Dirk J; Kingham, T Peter; Jarnagin, William R; van Gulik, Thomas M

    2016-01-01

    Background and study aims Preoperative biliary drainage is often initiated with endoscopic retrograde cholangiopancreatography (ERCP) in patients with potentially resectable perihilar cholangiocarcinoma (PHC), but additional percutaneous transhepatic catheter (PTC) drainage is frequently required. This study aimed to develop and validate a prediction model to identify patients with a high risk of inadequate ERCP drainage. Patients and Methods Patients with potentially resectable PHC and preoperative (attempted) ERCP drainage were included from two specialty center cohorts between 2001 and 2013. Indications for additional PTC drainage were failure to place an endoscopic stent, failure to relieve jaundice, cholangitis, or insufficient drainage of the future liver remnant. A prediction model was derived from the European cohort and externally validated in the USA cohort. Results 108 of 288 patients (38%) required additional preoperative PTC after inadequate ERCP drainage. Independent risk factors for additional PTC were proximal biliary obstruction on preoperative imaging (Bismuth 3 or 4) and pre-drainage total bilirubin level. The prediction model identified three subgroups: patients with a low risk of 7%, a moderate risk of 40%, and a high risk of 62%. The high-risk group consisted of patients with a total bilirubin level above 150 μmol/L and Bismuth 3a or 4 tumours, who typically require preoperative drainage of the angulated left bile ducts. The prediction model had good discrimination (AUC 0.74) and adequate calibration in the external validation cohort. Conclusions Selected patients with potentially resectable PHC have a high risk (62%) of inadequate preoperative ERCP drainage requiring additional PTC. These patients might do better with initial PTC instead of ERCP. PMID:26382308

  11. Geriatric Assessment-Identified Deficits in Older Cancer Patients With Normal Performance Status

    PubMed Central

    Deal, Allison M.; Nyrop, Kirsten A.; Williams, Grant R.; Pergolotti, Mackenzi; Wood, William A.; Alston, Shani M.; Gordon, Brittaney-Belle E.; Dixon, Samara A.; Moore, Susan G.; Taylor, W. Chris; Messino, Michael; Muss, Hyman B.

    2015-01-01

    Background. We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%–100%) on the Karnofsky performance status (KPS) scale. Methods. Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. Results. The sample included 984 patients: mean age was 73 years (range: 65–99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. Conclusion. Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes. PMID:25765876

  12. Modeling strategy to identify patients with primary immunodeficiency utilizing risk management and outcome measurement.

    PubMed

    Modell, Vicki; Quinn, Jessica; Ginsberg, Grant; Gladue, Ron; Orange, Jordan; Modell, Fred

    2017-02-21

    This study seeks to generate analytic insights into risk management and probability of an identifiable primary immunodeficiency defect. The Jeffrey Modell Centers Network database, Jeffrey Modell Foundation's 10 Warning Signs, the 4 Stages of Testing Algorithm, physician-reported clinical outcomes, programs of physician education and public awareness, the SPIRIT® Analyzer, and newborn screening, taken together, generates P values of less than 0.05%. This indicates that the data results do not occur by chance, and that there is a better than 95% probability that the data are valid. The objectives are to improve patients' quality of life, while generating significant reduction of costs. The advances of the world's experts aligned with these JMF programs can generate analytic insights as to risk management and probability of an identifiable primary immunodeficiency defect. This strategy reduces the uncertainties related to primary immunodeficiency risks, as we can screen, test, identify, and treat undiagnosed patients. We can also address regional differences and prevalence, age, gender, treatment modalities, and sites of care, as well as economic benefits. These tools support high net benefits, substantial financial savings, and significant reduction of costs. All stakeholders, including patients, clinicians, pharmaceutical companies, third party payers, and government healthcare agencies, must address the earliest possible precise diagnosis, appropriate intervention and treatment, as well as stringent control of healthcare costs through risk assessment and outcome measurement. An affected patient is entitled to nothing less, and stakeholders are responsible to utilize tools currently available. Implementation offers a significant challenge to the entire primary immunodeficiency community.

  13. Multiple gene mutations identified in patients infected with influenza A (H7N9) virus

    PubMed Central

    Chen, Cuicui; Wang, Mingbang; Zhu, Zhaoqin; Qu, Jieming; Xi, Xiuhong; Tang, Xinjun; Lao, Xiangda; Seeley, Eric; Li, Tao; Fan, Xiaomei; Du, Chunling; Wang, Qin; Yang, Lin; Hu, Yunwen; Bai, Chunxue; Zhang, Zhiyong; Lu, Shuihua; Song, Yuanlin; Zhou, Wenhao

    2016-01-01

    Influenza A (H7N9) virus induced high mortality since 2013. It is important to elucidate the potential genetic variations that contribute to virus infection susceptibilities. In order to identify genetic mutations that might increase host susceptibility to infection, we performed exon sequencing and validated the SNPS by Sanger sequencing on 18 H7N9 patients. Blood samples were collected from 18 confirmed H7N9 patients. The genomic DNA was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Genome analysis Tool. SNPs were verified by independent Sanger sequencing. The DAVID database and the DAPPLE database were used to do bioinformatics analysis. Through exon sequencing and Sanger sequencing, we identified 21 genes that were highly associated with H7N9 influenza infection. Protein-protein interaction analysis showed that direct interactions among genetic products were significantly higher than expected (p = 0.004), and DAVID analysis confirmed the defense-related functions of these genes. Gene mutation profiles of survived and non-survived patients were similar, suggesting some of genes identified in this study may be associated with H7N9 influenza susceptibility. Host specific genetic determinants of disease severity identified by this approach may provide new targets for the treatment of H7N9 influenza. PMID:27156515

  14. Can simple clinical features be used to identify patients with severe carotid stenosis on Doppler ultrasound?

    PubMed Central

    Mead, G.; Wardlaw, J.; Lewis, S.; McDowall, M.; Dennis, M.

    1999-01-01

    OBJECTIVES—Carotid endarterectomy reduces the risk of stroke in symptomatic patients with severe ipsilateral carotid stenosis. Symptomatic patients should therefore undergo carotid Doppler imaging, but in some centres access to imaging is limited. It was therefore investigated whether simple clinical features alone or in combination could be used to identify patients with severe carotid stenosis, so that they could be referred preferentially for carotid imaging.
METHODS—1041 patients with acute stroke, cerebral or retinal transient ischaemic attacks, and retinal strokes admitted to Western General Hospital or seen in neurovascular clinics were assessed by a stroke physician. Their carotid arteries were investigated using colour Doppler imaging by a consultant neuroradiologist. Patients with primary intracerebral haemorrhage, total anterior circulation strokes, posterior circulation strokes, or posterior circulation transient ischaemic attacks were excluded because carotid surgery would be inappropriate.
RESULTS—726 patients were used in the analysis. Stepwise logistic regression showed that there were significant positive associations between severe carotid stenosis and an ipsilateral bruit, diabetes mellitus, and previous transient ischaemic attacks; and a negative association with lacunar events. The strategy with the highest specificity (97%) was "any three of these four features" but sensitivity was only 17%. The strategy with the highest sensitivity (99%) was to use one or more of the four features, but specificity was only 22%.
CONCLUSION—None of the strategies identified all patients with severe carotid stenosis with a reasonable specificity. When access to carotid imaging is severely limited, simple clinical features are of some use in prioritising patients for imaging, but access to carotid imaging should be improved. 

 PMID:9886444

  15. Analyzing treatment aggressiveness and identifying high-risk patients in diabetic foot ulcer return to care.

    PubMed

    Remington, Austin C; Hernandez-Boussard, Tina; Warstadt, Nicholus M; Finnegan, Micaela A; Shaffer, Robyn; Kwong, Jereen Z; Curtin, Catherine

    2016-07-01

    Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all-cause 30-day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30-day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011-2012. All-cause 30-day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high-risk for readmission can improve counseling and

  16. Assessment of the Sensitivity, Specificity, and Accuracy of Thermography in Identifying Patients with TMD

    PubMed Central

    Woźniak, Krzysztof; Szyszka-Sommerfeld, Liliana; Trybek, Grzegorz; Piątkowska, Dagmara

    2015-01-01

    Background The purpose of the present study was to evaluate the sensitivity, specificity, and accuracy of thermography in identifying patients with temporomandibular dysfunction (TMD). Material/Methods The study sample consisted of 50 patients (27 women and 23 men) ages 19.2 to 24.5 years (mean age 22.43±1.04) with subjective symptoms of TMD (Ai II–III) and 50 patients (25 women and 25 men) ages 19.3 to 25.1 years (mean age 22.21±1.18) with no subjective symptoms of TMD (Ai I). The anamnestic interviews were conducted according to the three-point anamnestic index of temporomandibular dysfunction (Ai). The thermography was performed using a ThermaCAM TMSC500 (FLIR Systems AB, Sweden) independent thermal vision system. Thermography was closely combined with a 10-min chewing test. Results The results of our study indicated that the absolute difference in temperature between the right and left side (ΔT) has the highest diagnostic value. The diagnostic effectiveness of this parameter increased after the chewing test. The cut-off points for values of temperature differences between the right and left side and identifying 95.5% of subjects with no functional disorders according to the temporomandibular dysfunction index Di (specificity 95.5%) were 0.26°C (AUC=0.7422, sensitivity 44.3%, accuracy 52.4%) before the chewing test and 0.52°C (AUC=0.7920, sensitivity 46.4%, accuracy 56.3%) after it. Conclusions The evaluation of thermography demonstrated its diagnostic usefulness in identifying patients with TMD with limited effectiveness. The chewing test helped in increasing the diagnostic efficiency of thermography in identifying patients with TMD. PMID:26002613

  17. Comparing the Ability of Anthropometric Indicators in Identifying Metabolic Syndrome in HIV Patients

    PubMed Central

    Beraldo, Rebeca Antunes; Meliscki, Gabriela Cristina; Silva, Bruna Ramos; Navarro, Anderson Marliere; Bollela, Valdes Roberto; Schmidt, André; Foss-Freitas, Maria Cristina

    2016-01-01

    Background Highly active antiretroviral therapy (HAART) can cause side effects in HIV patients, as the metabolic syndrome. Early identification of risk for development of cardiovascular diseases using available reliable and practical methods is fundamental. On this basis, the aim of this study was to compare the effectiveness of anthropometric indicators to identify metabolic syndrome in HIV patients on HAART. Methods It is a cross-sectional study. A number of 280 stable HIV patients were studied. It measured weight, height, waist circumference (WC), hip circumference (HP), thigh circumference (TC) and calculated body mass index (BMI), body adiposity index (BAI), waist to hip ratio (WHR) and waist to thigh ratio (WTR). There was also a performance of biochemical tests of lipid profile and fasting glucose. Systemic blood pressure was measured. The criteria proposed by the National Cholesterol Education Program III (NCEP-ATP III) to metabolic syndrome classification was used. Individuals were divided in groups with or without metabolic alterations and their anthropometric indicators were compared. Receiver operating characteristic (ROC) curves were designed for each anthropometric indicator using the metabolic syndrome classification to identify sensitivity and specificity. Results WC was a good tool to identify each metabolic disorder separately: total cholesterol (only females, p<0.05), triglycerides (only males, p<0.001), HDL cholesterol (p<0.05), LDL cholesterol (p<005) and fasting glycemic (p<005). WC also showed the best performance to identify metabolic syndrome in both genders (areas under the curve (AUCs): 0.79 and 0.76 for male and female, respectively), while BAI proved to be an inadequate indicator (AUCs: 0.63 and 0.67 for males and females), respectively, in this population. Conclusions The central adiposity measure (WC) had the best performance to identify metabolic syndrome, and it is a convenient, cheap and reliable tool that can be used in clinical

  18. Correspondence between Pigmented Lesions Identified by Melanoma Patients Trained to Perform Partner-Assisted Skin Self-Examination and Dermatological Examination

    PubMed Central

    Stapleton, Jerod L.; Turrisi, Rob; Mallett, Kimberly A.; Robinson, June K.

    2015-01-01

    Background Skin-self examination (SSE) training interventions can increase understanding of melanoma early detection criteria and promote SSE. However, there remains a need to evaluate whether intervention participants can apply such early detection skills to accurately identify concerning, or potentially malignant, pigmented lesions during full body SSE. Methods We assessed SSE accuracy using data from a randomized control trial of a SSE skills training intervention designed to promote partner-assisted SSE among melanoma patients. In the trial, patient-partner pairs were administered the training intervention and performed monthly SSE to identify, evaluate, and track concerning pigmented skin lesions. Patients received a total body skin examination by a dermatologist approximately 4-months post-intervention. SSE accuracy was assessed as the correspondence between the specific concerning pigmented lesions identified by 274 study pairs during SSE with those identified during dermatological examination. We also examined whether lesions that were biopsied during the study were identified prior to biopsy during SSE. Results Approximately 3 in 4 of the concerning lesions identified by pairs during SSE were also identified during the dermatological exam. There were 81 biopsies performed during the study and pairs had identified 73% of the corresponding lesions during SSE. Of the 5 melanoma detected, 3 were identified during SSE. Conclusion Melanoma patients and partner taught to do SSE using an evidence-based program developed a high degree of correspondence with the study dermatologist in identifying concerning lesions. Impact This study provides novel evidence that supports the accuracy of full-body SSE for the patient identification of concerning lesions. PMID:26063475

  19. Identifying multiple myeloma patients using data from the French health insurance databases

    PubMed Central

    Palmaro, Aurore; Gauthier, Martin; Conte, Cécile; Grosclaude, Pascale; Despas, Fabien; Lapeyre-Mestre, Maryse

    2017-01-01

    Abstract This study aimed to assess the performance of several algorithms based on hospital diagnoses and the long-term diseases scheme to identify multiple myeloma patients. Potential multiple myeloma patients in 2010 to 2013 were identified using the presence of hospital records with at least 1 main diagnosis code for multiple myeloma (ICD-10 “C90”). Alternative algorithms also considered related and associated diagnoses, combination with long-term conditions, or at least 2 diagnoses. Incident patients were those with no previous “C90” codes in the past 24 or 12 months. The sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) were computed, using a French cancer registry for the corresponding area and period as the criterion standard. Long-term conditions data extracted concerned 11,559 patients (21,846 for hospital data). The registry contained 125 cases of multiple myeloma. Sensitivity was 70% when using only main hospital diagnoses (specificity 100%, PPV 79%), 76% when also considering related diagnoses (specificity 100%, PPV 74%), and 90% with associated diagnoses included (100% specificity, 64% PPV). In relation with their good performance, selected algorithms can be used to study the benefit and risk of drugs in treated multiple myeloma patients. PMID:28328805

  20. Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute promyelocytic leukemia patients.

    PubMed

    Breccia, Massimo; De Propris, Maria Stefania; Minotti, Clara; Stefanizzi, Caterina; Raponi, Sara; Colafigli, Gioia; Latagliata, Roberto; Guarini, Anna; Foà, Robin

    2014-02-01

    Limited information is available on the relationship between expression of some additional aberrant phenotypic features and outcome of acute promyelocytic leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and CD56 expression, and their prognostic value in a large series of APL patients. One hundred and fourteen adult patients consecutively diagnosed with PML/RARα-positive APL and homogeneously treated with the AIDA induction schedule at a single institution were included in the study. Twelve (10.5%) and 9 (8%) of the 114 patients expressed CD15 and CD56, respectively. CD15 expression identified a subset of patients with a classic morphologic subtype (92%), a prevalent association with a bcr1 expression (67%) with an unexpectedly higher frequency of relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56 expression was detected only in patients with a classic morphologic subtype, a prevalent bcr3 expression (67%), high incidence of differentiation syndrome (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04) and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the negative prognostic value of CD56 and we show that the same applies also to cases expressing CD15. These aberrant markers may be considered for the refinement of risk-adapted therapeutic strategies in APL patients.

  1. Characterization of regulatory T cells identified as CD4+CD25highCD39+ in patients with active tuberculosis

    PubMed Central

    Chiacchio, T; Casetti, R; Butera, O; Vanini, V; Carrara, S; Girardi, E; Di Mitri, D; Battistini, L; Martini, F; Borsellino, G; Goletti, D

    2009-01-01

    Forkhead box P3 (FoxP3) is a transcription factor whose expression characterizes regulatory T cells (Treg), but it is also present on activated T cells, thus hindering correct Treg identification. Using classical markers for Treg recognition, discordant results were found in terms of Treg expansion during active tuberculosis (TB) disease. Recently CD39 has been shown to be an accurate marker for Treg detection. The objectives of this study were: (i) to identify Treg expressing CD39 in patients with TB and to compare the results with those obtained by the standard phenotypic markers; (ii) to evaluate if Treg are expanded in vitro by exogenous interleukin (IL)-2 or by antigen-specific stimulation; and (iii) to characterize Treg function on the modulation of antigen-specific responses. We enrolled 13 patients with pulmonary TB and 12 healthy controls. Treg were evaluated by flow cytometry ex vivo and after antigen-specific in vitro stimulation using CD25, FoxP3, CD127 and CD39 markers. Results indicate that CD39+ cells within the CD4+CD25high cells have Treg properties (absence of interferon-γ production and transforming growth factor-β1 release upon stimulation). Ex vivo analysis did not show significant differences between TB patients and controls of Treg by classical or novel markers. In contrast, a significantly higher percentage of Treg was found in TB patients after antigen-specific stimulation both in the presence or absence of IL-2. Depletion of CD39+ Treg increased RD1-specific responses significantly. In conclusion, CD39 is an appropriate marker for Treg identification in TB. These results can be useful for future studies to monitor Mycobacterium tuberculosis-specific response during TB. PMID:19438599

  2. A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients.

    PubMed

    Afroz, Sumbul; Giddaluru, Jeevan; Vishwakarma, Sandeep; Naz, Saima; Khan, Aleem Ahmed; Khan, Nooruddin

    2017-01-01

    Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.

  3. Genetic screening of Greek patients with Huntington’s disease phenocopies identifies an SCA8 expansion.

    PubMed

    Koutsis, G; Karadima, G; Pandraud, A; Sweeney, M G; Paudel, R; Houlden, H; Wood, N W; Panas, M

    2012-09-01

    Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.

  4. Accurate Measurements of the Skin Surface Area of the Healthy Auricle and Skin Deficiency in Microtia Patients

    PubMed Central

    van Doremalen, Rob F. M.; Melchels, Ferry P. W.; Kolodzynski, Michail N.; Pouran, Behdad; Malda, Jos; Kon, Moshe; Breugem, Corstiaan C.

    2016-01-01

    Background: The limited cranial skin covering auricular implants is an important yet underrated factor in auricular reconstruction for both reconstruction surgery and tissue engineering strategies. We report exact measurements on skin deficiency in microtia patients and propose an accessible preoperative method for these measurements. Methods: Plaster ear models (n = 11; male:female = 2:1) of lobular-type microtia patients admitted to the University Medical Center Utrecht in The Netherlands were scanned using a micro-computed tomographic scanner or a cone-beam computed tomographic scanner. The resulting images were converted into mesh models from which the surface area could be calculated. Results: The mean total skin area of an adult-size healthy ear was 47.3 cm2, with 49.0 cm2 in men and 44.3 cm2 in women. Microtia ears averaged 14.5 cm2, with 15.6 cm2 in men and 12.6 cm2 in women. The amount of skin deficiency was 25.4 cm2, with 26.7 cm2 in men and 23.1 cm2 in women. Conclusions: This study proposes a novel method to provide quantitative data on the skin surface area of the healthy adult auricle and the amount of skin deficiency in microtia patients. We demonstrate that the microtia ear has less than 50% of skin available compared with healthy ears. Limited skin availability in microtia patients can lead to healing problems after auricular reconstruction and poses a significant challenge in the development of tissue-engineered cartilage implants. The results of this study could be used to evaluate outcomes and investigate new techniques with regard to tissue-engineered auricular constructs. PMID:28293505

  5. PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.

    PubMed

    Gros, Alena; Robbins, Paul F; Yao, Xin; Li, Yong F; Turcotte, Simon; Tran, Eric; Wunderlich, John R; Mixon, Arnold; Farid, Shawn; Dudley, Mark E; Hanada, Ken-Ichi; Almeida, Jorge R; Darko, Sam; Douek, Daniel C; Yang, James C; Rosenberg, Steven A

    2014-05-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8⁺ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8⁺ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8⁺ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8⁺ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8⁺ lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCRβ deep sequencing revealed oligoclonal expansion of specific TCRβ clonotypes in CD8⁺PD-1⁺ compared with CD8⁺PD-1- TIL populations. Furthermore, the most highly expanded TCRβ clonotypes in the CD8⁺ and the CD8⁺PD-1⁺ populations recognized the autologous tumor and included clonotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8⁺ TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment.

  6. Preoperative psychological assessment of patients seeking weight-loss surgery: identifying challenges and solutions

    PubMed Central

    Edwards-Hampton, Shenelle A; Wedin, Sharlene

    2015-01-01

    Preoperative psychosocial assessment is the standard of care for patients seeking weight-loss surgery (WLS). However, the assessment procedure varies widely by surgery site. Comprehensive assessments can provide a wealth of information that assists both the patient and the treatment team, anticipate and prepare for challenges associated with extensive behavioral and lifestyle changes that are required postsurgery. In this review, we provide an overview of the purpose of the preoperative psychosocial assessment and domains to be included. Challenges commonly identified in the assessment are discussed, including maladaptive eating behaviors, psychiatric comorbidities, and alcohol use. Potential solutions and approaches to these challenges are provided. Additionally, patient populations requiring special consideration are presented to include adolescents, those with cognitive vulnerabilities, and aging adults. PMID:26604844

  7. Whole-Exome Sequencing Identifies Novel Somatic Mutations in Chinese Breast Cancer Patients

    PubMed Central

    Zhang, Yanfeng; Cai, Qiuyin; Shu, Xiao-Ou; Gao, Yu-Tang; Li, Chun; Zheng, Wei; Long, Jirong

    2016-01-01

    Most breast cancer genomes harbor complex mutational landscapes. Somatic alterations have been predominantly discovered in breast cancer patients of European ancestry; however, little is known about somatic aberration in patients of other ethnic groups including Asians. In the present study, whole-exome sequencing (WES) was conducted in DNA extracted from tumor and matched adjacent normal tissue samples from eleven early onset breast cancer patients who were included in the Shanghai Breast Cancer Study. We discovered 159 somatic missense and ten nonsense mutations distributed among 167 genes. The most frequent 50 somatic mutations identified by WES were selected for validation using Sequenom MassARRAY system in the eleven breast cancer patients and an additional 433 tumor and 921 normal tissue/blood samples from the Shanghai Breast Cancer Study. Among these 50 mutations selected for validation, 32 were technically validated. Within the validated mutations, somatic mutations in the TRPM6, HYDIN, ENTHD1, and NDUFB10 genes were found in two or more tumor samples in the replication stage. Mutations in the ADRA1B, CBFB, KIAA2022, and RBM25 genes were observed once in the replication stage. To summarize, this study identified some novel somatic mutations for breast cancer. Future studies will need to be conducted to determine the function of these mutations/genes in the breast carcinogenesis. PMID:26870154

  8. A review of approaches to identifying patient phenotype cohorts using electronic health records

    PubMed Central

    Shivade, Chaitanya; Raghavan, Preethi; Fosler-Lussier, Eric; Embi, Peter J; Elhadad, Noemie; Johnson, Stephen B; Lai, Albert M

    2014-01-01

    Objective To summarize literature describing approaches aimed at automatically identifying patients with a common phenotype. Materials and methods We performed a review of studies describing systems or reporting techniques developed for identifying cohorts of patients with specific phenotypes. Every full text article published in (1) Journal of American Medical Informatics Association, (2) Journal of Biomedical Informatics, (3) Proceedings of the Annual American Medical Informatics Association Symposium, and (4) Proceedings of Clinical Research Informatics Conference within the past 3 years was assessed for inclusion in the review. Only articles using automated techniques were included. Results Ninety-seven articles met our inclusion criteria. Forty-six used natural language processing (NLP)-based techniques, 24 described rule-based systems, 41 used statistical analyses, data mining, or machine learning techniques, while 22 described hybrid systems. Nine articles described the architecture of large-scale systems developed for determining cohort eligibility of patients. Discussion We observe that there is a rise in the number of studies associated with cohort identification using electronic medical records. Statistical analyses or machine learning, followed by NLP techniques, are gaining popularity over the years in comparison with rule-based systems. Conclusions There are a variety of approaches for classifying patients into a particular phenotype. Different techniques and data sources are used, and good performance is reported on datasets at respective institutions. However, no system makes comprehensive use of electronic medical records addressing all of their known weaknesses. PMID:24201027

  9. Thirty-nine novel neurofibromatosis 1 (NF1) gene mutations identified in Slovak patients.

    PubMed

    Nemethova, Martina; Bolcekova, Anna; Ilencikova, Denisa; Durovcikova, Darina; Hlinkova, Katarina; Hlavata, Anna; Kovacs, Laszlo; Kadasi, Ludevit; Zatkova, Andrea

    2013-09-01

    We performed a complex analysis of the neurofibromatosis type 1 (NF1) gene in Slovakia based on direct cDNA sequencing supplemented by multiple ligation dependent probe amplification (MLPA) analysis. All 108 patients had café-au-lait spots, 85% had axilary and/or inguinal freckling, 61% neurofibromas, 36% Lisch nodules of the iris and 31% optic pathway glioma, 5% suffered from typical skeletal disorders, and 51% of patients had family members with NF1. In 78 of the 86 (90.7%) index patients our analysis revealed the presence of NF1 mutations, 68 of which were small changes (87.2%), including 39 (50%) novel. Among the identified mutations the most prevalent were small deletions and insertions causing frameshift (42.3%), followed by nonsense (14.1%), missense (12.8%), and typical splicing (11.5%) mutations. Type 1 NF1 deletions and intragenic deletions/duplication were identified in five cases each (6.4%). Interestingly, in five other cases nontypical splicing variants were found, whose real effect on NF1 transcript would have remained undetected if using a DNA-based method alone, thus underlying the advantage of using the cDNA-based sequencing. We show that Slovak NF1 patients have a similar repertoire of NF1 germline mutations compared to other populations, with some prevalence of small deletions/insertions and a decreased proportion of nonsense mutations.

  10. An algorithm to identify patients with treated type 2 diabetes using medico-administrative data

    PubMed Central

    2011-01-01

    Background National authorities have to follow the evolution of diabetes to implement public health policies. An algorithm was developed to identify patients with treated type 2 diabetes and estimate its annual prevalence in Luxembourg using health insurance claims when no diagnosis code is available. Methods The DIABECOLUX algorithm was based on patients' age as well as type and number of hypoglycemic agents reimbursed between 1995 and 2006. Algorithm validation was performed using the results of a national study based on medical data. Sensitivity, specificity and predictive values were estimated. Results The sensitivity of the DIABECOLUX algorithm was found superior to 98.2%. Between 2000 and 2006, 22,178 patients were treated for diabetes in Luxembourg, among whom 21,068 for type 2 diabetes (95%). The prevalence was estimated at 3.79% in 2006 and followed an increasing linear trend during the period. In 2005, the prevalence was low for young age classes and increased rapidly from 40 to 70 for male and 80 for female, reaching a peak of, respectively 17.0% and 14.3% before decreasing. Conclusions The DIABECOLUX algorithm is relevant to identify treated type 2 diabetes patients. It is reproducible and should be transferable to every country using medico-administrative databases not including diagnosis codes. Although undiagnosed patients and others with lifestyle recommendations only were not considered in this study, this algorithm is a cheap and easy-to-use tool to inform health authorities. Further studies will use this tool with the aim of improving the quality of health care dedicated to diabetic patients in Luxembourg. PMID:21492480

  11. A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients

    PubMed Central

    Afroz, Sumbul; Giddaluru, Jeevan; Vishwakarma, Sandeep; Naz, Saima; Khan, Aleem Ahmed; Khan, Nooruddin

    2017-01-01

    Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients’ (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA. PMID:28210261

  12. Performance of Claims-Based Algorithms for Identifying Heart Failure and Cardiomyopathy Among Patients Diagnosed with Breast Cancer

    PubMed Central

    Allen, Larry A.; Yood, Marianne Ulcickas; Wagner, Edward H.; Bowles, Erin J. Aiello; Pardee, Roy; Wellman, Robert; Habel, Laurel; Nekhlyudov, Larissa; Davis, Robert L.; Adedayo, Onitilo; Magid, David J.

    2012-01-01

    Background Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information. Objective To characterize the performance of claims-based algorithms for identification of cardiac dysfunction in a cancer population. Research Design We sampled 400 charts among 6,460 women diagnosed with incident breast cancer, tumor size ≥2 cm or node positivity, treated within 8 US health care systems during 1999–2007. We abstracted medical records for clinical diagnoses of heart failure (HF) and cardiomyopathy (CM) or evidence of reduced left ventricular ejection fraction. We then assessed the performance of 3 different ICD-9-based algorithms. Results The HF/CM coding algorithm designed a priori to balance performance characteristics provided a sensitivity of 62% (95% confidence interval 40–80%), specificity of 99% (97–99%), positive predictive value (PPV) of 69% (45–85%), and negative predictive value (NPV) of 98% (96–99%). When applied only to incident HF/CM (ICD-9 codes and gold standard diagnosis both appearing after breast cancer diagnosis) in patients exposed to anthracycline and/or trastuzumab therapy the PPV was 42% (14–76%). Conclusions Claims-based algorithms have moderate sensitivity and high specificity for identifying HF/CM among patients with invasive breast cancer. Because the prevalence of HF/CM among the breast cancer population is low, ICD-9 codes have high NPV but only moderate PPV. These findings suggest a significant degree of misclassification due to HF/CM overcoding versus incomplete clinical documentation of HF/CM in the medical record. PMID:22643199

  13. Utility of the Edmonton Frail Scale in identifying frail elderly patients during treatment of colorectal cancer

    PubMed Central

    Meyers, Brandon M.; Al-Shamsi, Humaid O.; Rask, Sara; Yelamanchili, Radhika; Phillips, Callista M.; Papaioannou, Alexandra; Pond, Gregory R.; Jeyabalan, Neera; Zbuk, Kevin M.

    2017-01-01

    Background Frailty has been proposed by geriatricians as an indicator of functional age. The Edmonton Frail Scale (EFS) is a 15-point incremental scale; it is quick (<5 min), and simple to administer. We conducted an exploratory study to establish if the EFS add utility to clinician’s expertise by determining if there was an association between EFS and receipt of chemotherapy in colorectal cancer (CRC) patients. Methods The EFS was administered to stage II–IV CRC patients ≥70 years. EFS assessment was completed by one of the investigators, with the treating oncology team blinded to the results. Results A total of 46 patients were enrolled, and the EFS was reproduced in 32 patients at two visits (r=0.81; 95% CI: 0.64–0.90, P<0.0001). There was no correlation between the EFS and receipt of chemotherapy for the study population as a whole; however, exclusion of stage II patients showed a reduced likelihood of receiving chemotherapy with higher EFS scores (odds ratio 0.56; 95% CI: 0.37–0.85, P<0.01 per unit increment). A similar effect was observed after multivariable analysis (adjusting for performance status, age, stage and gender, odds ratio 0.41 95% CI: 0.18–0.96, P<0.05 per unit increment). Conclusions This exploratory study suggests that EFS can identify patients that oncologists may have thought were too frail for chemotherapy, independent of PS. Therefore, the EFS has the potential to add a reproducible, and quantifiable measure of frailty to the clinician’s decision making toolset. A follow up study will employ the EFS in real-time, and determine if using the EFS can minimize complications and unplanned health care utilization in elderly cancer patients. PMID:28280606

  14. Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.

    PubMed

    Morgado de Abreu, M A M; Roselino, A M; Enokihara, M; Nonogaki, S; Prestes-Carneiro, L E; Weckx, L L M; Alchorne, M M A

    2014-01-01

    In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.

  15. Protocol for a scoping review study to identify and classify patient-centred quality indicators

    PubMed Central

    Jolley, Rachel J; Lorenzetti, Diane L; Manalili, Kimberly; Lu, Mingshan; Santana, Maria J

    2017-01-01

    Introduction The concept of patient-centred care (PCC) is changing the way healthcare is understood, accepted and delivered. The Institute of Medicine has defined PCC as 1 of its 6 aims to improve healthcare quality. However, in Canada, there are currently no nationwide standards in place for measuring and evaluating healthcare from a patient-centred approach. In this paper, we outline our scoping review protocol to systematically review published and unpublished literature specific to patient-centred quality indicators that have been implemented and evaluated across various care settings. Methods and analysis Arksey and O'Malley's scoping review methodology framework will guide the conduct of this scoping review. We will search electronic databases (MEDLINE, EMBASE, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Social Work Abstracts, Social Services Abstracts), grey literature sources and the reference lists of key studies to identify studies appropriate for inclusion. 2 reviewers will independently screen all abstracts and full-text studies for inclusion. We will include any study which focuses on quality indicators in the context of PCC. All bibliographic data, study characteristics and indicators will be collected and analysed using a tool developed through an iterative process by the research team. Indicators will be classified according to a predefined conceptual framework and categorised and described using qualitative content analysis. Ethics and dissemination The scoping review will synthesise patient-centred quality indicators and their characteristics as described in the literature. This review will be the first step to formally identify what quality indicators have been used to evaluate PCC across the healthcare continuum, and will be used to inform a stakeholder consensus process exploring the development of a generic set of patient-centred quality indicators applicable to multiple care settings. The

  16. Study Of Physician And Patient Communication Identifies Missed Opportunities To Help Reduce Patients' Out-Of-Pocket Spending.

    PubMed

    Ubel, Peter A; Zhang, Cecilia J; Hesson, Ashley; Davis, J Kelly; Kirby, Christine; Barnett, Jamison; Hunter, Wynn G

    2016-04-01

    Some experts contend that requiring patients to pay out of pocket for a portion of their care will bring consumer discipline to health care markets. But are physicians prepared to help patients factor out-of-pocket expenses into medical decisions? In this qualitative study of audiorecorded clinical encounters, we identified physician behaviors that stand in the way of helping patients navigate out-of-pocket spending. Some behaviors reflected a failure to fully engage with patients' financial concerns, from never acknowledging such concerns to dismissing them too quickly. Other behaviors reflected a failure to resolve uncertainty about out-of-pocket expenses or reliance on temporary solutions without making long-term plans to reduce spending. Many of these failures resulted from systemic barriers to health care spending conversations, such as a lack of price transparency. For consumer health care markets to work as intended, physicians need to be prepared to help patients navigate out-of-pocket expenses when financial concerns arise during clinical encounters.

  17. ALTERATIONS IN MUCOSAL IMMUNITY IDENTIFIED IN THE COLON OF PATIENTS WITH IRRITABLE BOWEL SYNDROME

    PubMed Central

    Aerssens, Jeroen; Camilleri, Michael; Talloen, Willem; Thielemans, Leen; Göhlmann, Hinrich W. H.; Wyngaert, Ilse Van den; Thielemans, Theo; de Hoogt, Ronald; Andrews, Christopher N.; Bharucha, Adil E.; Carlson, Paula J.; Busciglio, Irene; Burton, Duane D.; Smyrk, Thomas; Urrutia, Raul; Coulie, Bernard

    2008-01-01

    BACKGROUND & AIMS Irritable bowel syndrome (IBS) has been associated with mucosal dysfunction,, mild inflammation, and altered colonic bacteria. We used microarray expression profiling of sigmoid colon mucosa to assess whether there are stably expressed sets of genes that suggest there are objective molecular biomarkers associated with IBS. METHODS Gene expression profiling was performed using Affymetrix GeneChips with RNA from sigmoid colon mucosal biopsies from 36 IBS patients and 25 healthy control subjects. RTQ-PCR was used to confirm the data in 12 genes of interest. Statistical methods for microarray data were applied to search for differentially expressed genes, and to assess the stability of molecular signatures in IBS patients. RESULTS Mucosal gene expression profiles were consistent across different sites within the sigmoid colon and were stable on repeat biopsy over ~3 months. Differentially expressed genes suggest functional alterations of several components of the host mucosal immune response to microbial pathogens. The most strikingly increased expression involved a yet uncharacterized gene, DKFZP564O0823. Identified specific genes suggest the hypothesis that molecular signatures may enable distinction of a subset of IBS patients from healthy controls. Using 75% of the biopsies as a validation set to develop a gene profile, the test set (25%) was correctly predicted with ~70% accuracy. CONCLUSIONS Mucosal gene expression analysis shows there are relatively stable alterations in colonic mucosal immunity in IBS. These molecular alterations provide the basis to test the hypothesis that objective biomarkers may be identified in IBS and enhance understanding of the disease. PMID:18237869

  18. Engineering Approach to Identifying Patients with Colon Tumors on the Basis of Electrophotonic Imaging Technique Data

    PubMed Central

    Yakovleva, E.G.; Korotkov, K.G.; Fedorov, E.D.; Ivanova, E.V.; Plahov, R.V.; Belonosov, S.S.

    2016-01-01

    Background: Colonic neoplasms are quite a serious problem today. Screening methods play an important role in diagnosing the disease. Colorectal cancer screening is a complex undertaking, having various options, which require a lot of efforts both from the doctor and from the patient, including the use of sedatives and the necessity of the presence of an assistant for some procedures such as colonoscopy. This is why it is very important to find a method by which one can make a diagnosis quickly, easily, and painlessly. Methods: The ability to identify patients with tumors of the colon using the Electrophotonic Imaging (EPI) technique, as well as using it for differential diagnosis of tumors of the colon by their morphology, size and quantity was investigated. Selection of the most significant parameters of the EPI-graphy for the separation of the control group and the group of patients with tumors of the colon was developed. 137 people were studied with the EPI camera, with ages ranging from 16 to 86 years, including 49 males and 88 females. Based on the results of the colonoscopy and histological findings all subjects were divided into 2 groups: control group of 55 people, 9 males, 46 females; and patients with tumors (benign or malignant) of the colon - 82 people; 40 males and 42 females. Then all subjects were divided into smaller groups based on morphology, size, number of tumors and localization. Results: Based on the identified indicators decision rules to determine the patients with tumors of the colon were constructed. The specificity of the resulting function was 80.0% and sensitivity 75.6%. Decision rule was built as well with logistic regression. The specificity of the resulting function was 78.2% and sensitivity 90.0%. The accuracy of this approach was higher than using discriminant analysis. Conclusions: The results of this study have proven the ability to identify patients with tumors of the colon using EPI technology, as well as use it for

  19. A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias.

    PubMed

    Roy, Noémi B A; Wilson, Edward A; Henderson, Shirley; Wray, Katherine; Babbs, Christian; Okoli, Steven; Atoyebi, Wale; Mixon, Avery; Cahill, Mary R; Carey, Peter; Cullis, Jonathan; Curtin, Julie; Dreau, Helene; Ferguson, David J P; Gibson, Brenda; Hall, Georgina; Mason, Joanne; Morgan, Mary; Proven, Melanie; Qureshi, Amrana; Sanchez Garcia, Joaquin; Sirachainan, Nongnuch; Teo, Juliana; Tedgård, Ulf; Higgs, Doug; Roberts, David; Roberts, Irene; Schuh, Anna

    2016-10-01

    Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the 'discoverability' of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family.

  20. Combination of micro-dialysis and infrared spectroscopy: a multianalyte assay for accurate biofluid analysis and patient monitoring

    NASA Astrophysics Data System (ADS)

    Vahlsing, Thorsten; Delbeck, Sven; Budde, Janpeter; Ihrig, Dieter; Heise, H. Michael

    2016-03-01

    Micro-dialysis can be used for continuously harvesting body fluids, while a multi-component analysis of the dialysates by infrared spectrometry offers splendid opportunities for monitoring substrates and metabolites such as glucose, lactate and others small enough to penetrate the semi-permeable dialysis membranes. However, a drawback of this process are variable recovery rates, which can be observed especially for subcutaneously implanted catheters in human subjects. Isotonic perfusates were investigated with acetate and mannitol as recovery markers for the dialysis of human serum at 37°C to mimic in vivo patient monitoring. The latter non-ionic substance has been suggested for application when other ionic substances such as bicarbonate or pH are also to be determined. Simultaneously for acetate and mannitol, the depletion of the marker substances from the perfusates using different micro-dialysis devices was investigated under various flow-rates. Relationships between relative dialysate marker concentrations and glucose recovery rates were determined based on multivariate calibrations. For quantification, classical least squares with reference spectra for modelling the serum dialysates was used, rendering a basis for reliable blood glucose and lactate measurements.

  1. Tim-3 identifies exhausted follicular helper T cells in breast cancer patients.

    PubMed

    Zhu, Shiguang; Lin, Jun; Qiao, Guangdong; Wang, Xingmiao; Xu, Yanping

    2016-09-01

    Breast cancer is the most common cancer diagnosed in women worldwide. Although a series of treatment options have improved the overall 5-year survival rate to 90%, individual responses still vary from patient to patient. New evidence suggested that the infiltration of CXCL13-expressing CD4(+) follicular helper cells (Tfh) in breast tumor predicted better survival. Here, we examined the regulation of Tfh function in breast cancer patients in depth. We found that the frequencies of circulating Tfh cells were not altered in breast cancer patients compared to healthy controls. However, the expression of PD-1 and Tim-3 in Tfh cells was significantly elevated in breast cancer patients. Interestingly, we observed a preferential upregulation of PD-1 in Tim-3(+) Tfh cells compared to Tim-3(-) Tfh cells. Coexpression of PD-1 and Tim-3 is typically a hallmark of functional exhaustion in chronic virus infections and tumor. To examine whether Tim-3(+) identifies exhausted Tfh cells, we stimulated Tfh cells with anti-CD3/CD28, and found that Tim-3(+) T cells expressed reduced frequencies of chemokine CXCL13 and cytokine interleukin 21 (IL-21), and contained fewer proliferating cells, than Tim-3(-) Tfh cells. Compared to those cocultured with Tim-3(-) Tfh cells, naive B cells cocultured with Tim-3(+) Tfh cells resulted in significantly less IgM, IgG and IgA production after 12 day incubation, demonstrating a reduction in Tim-3(+) Tfh-mediated B cell help. Moreover, the frequencies of Tim-3(+) Tfh cells in resected breast tumor were further upregulated than autologous blood, suggesting a participation of Tim-3(+) Tfh cells in tumor physiology. Overall, the data presented here provided new insight in the regulation of Tfh cells in breast cancer patients.

  2. Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites

    PubMed Central

    Di Gangi, Iole Maria; Mazza, Tommaso; Fontana, Andrea; Copetti, Massimiliano; Fusilli, Caterina; Ippolito, Antonio; Mattivi, Fulvio; Latiano, Anna; Andriulli, Angelo

    2016-01-01

    Purpose pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Experimental Design Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. Materials and Methods Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). Conclusion Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials. PMID:26735340

  3. Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease

    PubMed Central

    Curto‐Barredo, Laia; Yelamos, Jose; Gimeno, Ramon; Mojal, Sergi; Pujol, Ramon M.

    2016-01-01

    Abstract Introduction The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. Methods We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. Results Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). Conclusions The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life. PMID:27980778

  4. Patient-identified events implicated in the development of body dysmorphic disorder.

    PubMed

    Weingarden, Hilary; Curley, Erin E; Renshaw, Keith D; Wilhelm, Sabine

    2017-03-08

    Little is known about the causes of body dysmorphic disorder (BDD), but researchers have proposed a diathesis-stress model. This study uses a patient-centered approach to identify stressful events to which patients attribute the development of their BDD symptoms. An Internet-recruited sample of 165 adults with BDD participated. A large minority of participants attributed the development of their BDD to a triggering event. Bullying experiences were the most commonly described type of event. Additionally, most events were interpersonal and occurred during grade school or middle school. There were no differences in severity of psychosocial outcomes between participants who did or did not attribute their BDD to a specific triggering event. However, participants who specifically attributed their BDD development to a bullying experience had poorer psychosocial outcomes (i.e., perceived social support, depression severity, functional impairment, quality of life) compared to those who attributed their BDD development to another type of triggering event.

  5. Coagulation abnormalities identified by thromboelastometry in patients with severe sepsis: the relationship to endotoxemia and mortality.

    PubMed

    Adamik, Barbara; Gozdzik, Waldemar; Jakubczyk, Dominika; Welna, Marek; Kübler, Andrzej

    2017-03-01

    The aim of this study was to monitor the development of coagulation abnormalities in patients with severe sepsis using thromboelastometry and to assess whether increased endotoxin activity was associated with a change in coagulation. Data collected on ICU admission, day 2, 3, and 4 were analysed in 61 patients. Thromboelastometry made it possible to identify patients with a normal (group 1), hypercoagulable (group 2), or hypocoagulable (group 3) pattern. The best accuracy of thromboelastometry parameters as potential indices of coagulation abnormalities was yielded by the clot formation time and maximum clot firmness. The mortality rate was low in group 1(16%) and the presence of abnormalities, indicating either a hyper or hypocoagulation pattern, was associated with significantly higher mortality (42 and 39% respectively; P = 0.05). In group 1, baseline endotoxin activity was low [0.22 endotoxin activity units (EAU), 0.15-0.43] and did not change significantly during the observation period. In group 2, baseline endotoxin activity was elevated (0.52 EAU (0.39-0.62)) and remained high on day 2, 3, and 4. In group 3, baseline endotoxin activity was elevated (0.56 EAU (0.28-0.80)) and similarly to group 2, remained high on day 2, 3, and 4. The presence of coagulation disorders indicates a high-risk subpopulation of critically ill patients as reflected in significantly higher mortality rates and increased endotoxin activity.

  6. Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors

    NASA Astrophysics Data System (ADS)

    Cho, Edward H.; Wendel, Marco; Luttgen, Madelyn; Yoshioka, Craig; Marrinucci, Dena; Lazar, Daniel; Schram, Ethan; Nieva, Jorge; Bazhenova, Lyudmila; Morgan, Alison; Ko, Andrew H.; Korn, W. Michael; Kolatkar, Anand; Bethel, Kelly; Kuhn, Peter

    2012-02-01

    Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE.

  7. Allergens from Fusarium solani identified by immunoblotting in asthma patients In Iran.

    PubMed

    Khosravi, Ali Reza; Fatahinia, Mahnaz; Shokri, Hojjatollah; Yadegari, Mohammad Hossein

    2012-03-01

    We extracted Fusarium solani antigens to evaluate specific anti-F. solani IgE in fifty-one patients with asthma (33 men and 18 women) and in 22 non-atopic healthy subjects (15 men and 7 women). F. solani strains were cultured in Sabouraud glucose agar and subjected to cell disruption using the freeze-and-thaw method. The obtained cytoplasmic extracts were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Sensitisation to F. solani antigens has been evaluated in asthmatic patients using the immunoblotting assay. The SDS-PAGE identified 29 protein bands in the cytoplasmic extracts of F. solani isolates, with molecular weights ranging from 24 kDa to 112 kDa. Immunoblotting detected specific anti-F. solani IgE antibody in all asthma patients, but not in the control group. The predominant reactive allergens in patients corresponded to the bands with molecular weights of 24 kDa, 58.5 kDa, 64.5 kDa, 69 kDa, 72 kDa, and 97 kDa. Our results suggest that various allergenic components of F. solani may produce symptoms of asthma in susceptible individuals and they call for further research.

  8. Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding

    PubMed Central

    Wong, Joshua G. X.; Thein, Tun Linn; Leo, Yee-Sin; Pang, Junxiong; Lye, David C.

    2016-01-01

    Background Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. Methods We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. Results On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9–4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27–2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94–2.12), ANC (aOR 1.3; 95% CI: 1.15–1.46), ALC (aOR 0.4; 95% CI: 0.25–0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92–1.002) and platelet count (aOR 0.993; 95% CI: 0.988–0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). Conclusion Clinical risk factors associated with clinically significant

  9. Creation of an idealized nasopharynx geometry for accurate computational fluid dynamics simulations of nasal airflow in patient-specific models lacking the nasopharynx anatomy.

    PubMed

    A T Borojeni, Azadeh; Frank-Ito, Dennis O; Kimbell, Julia S; Rhee, John S; Garcia, Guilherme J M

    2016-08-15

    Virtual surgery planning based on computational fluid dynamics (CFD) simulations has the potential to improve surgical outcomes for nasal airway obstruction patients, but the benefits of virtual surgery planning must outweigh the risks of radiation exposure. Cone beam computed tomography (CT) scans represent an attractive imaging modality for virtual surgery planning due to lower costs and lower radiation exposures compared with conventional CT scans. However, to minimize the radiation exposure, the cone beam CT sinusitis protocol sometimes images only the nasal cavity, excluding the nasopharynx. The goal of this study was to develop an idealized nasopharynx geometry for accurate representation of outlet boundary conditions when the nasopharynx geometry is unavailable. Anatomically accurate models of the nasopharynx created from 30 CT scans were intersected with planes rotated at different angles to obtain an average geometry. Cross sections of the idealized nasopharynx were approximated as ellipses with cross-sectional areas and aspect ratios equal to the average in the actual patient-specific models. CFD simulations were performed to investigate whether nasal airflow patterns were affected when the CT-based nasopharynx was replaced by the idealized nasopharynx in 10 nasal airway obstruction patients. Despite the simple form of the idealized geometry, all biophysical variables (nasal resistance, airflow rate, and heat fluxes) were very similar in the idealized vs patient-specific models. The results confirmed the expectation that the nasopharynx geometry has a minimal effect in the nasal airflow patterns during inspiration. The idealized nasopharynx geometry will be useful in future CFD studies of nasal airflow based on medical images that exclude the nasopharynx.

  10. Red Flags: Clinical Signs for Identifying Autoimmune Encephalitis in Psychiatric Patients

    PubMed Central

    Herken, Julia; Prüss, Harald

    2017-01-01

    Autoimmune mechanisms causing diverse psychiatric symptoms are increasingly recognized and brought about a paradigm shift in neuropsychiatry. Identification of underlying antibodies against neuronal ion channels or receptors led to the speculation that a number of patients go misdiagnosed with a primary psychiatric disease. However, there is no clear consensus which clinical signs in psychiatric patients should prompt further investigations including measurement of anti-neuronal autoantibodies. We therefore aimed to analyze the presenting symptoms in patients with autoimmune encephalitis and the time between symptom onset and initiation of antibody diagnostics. For this, we recruited 100 patients from the Charité Center for Autoimmune Encephalitis between May and October 2016, including all types of autoimmune encephalitides. Psychiatric abnormalities were the most common clinical symptoms and were the presenting sign in 60%. One-third of patients were initially hospitalized in a psychiatric ward. All patients positive for antibodies against the N-methyl-d-aspartate receptor showed behavioral changes, hallucinations, memory deficits, catatonia, or delusions. Patients positive for antibodies against other cell surface or intracellular antigens were often hospitalized with a psychosomatic diagnosis. The time between occurrence of first symptoms and antibody testing was often alarmingly prolonged. In patients with symptom onset between 2013 and 2016, the mean delay was 74 days, in cases diagnosed between 2007 and 2012 even 483 days, suggesting though that increased awareness of this novel disease group helped to expedite proper diagnosis and treatment. By analyzing the medical records in detail, we identified clinical signs that may help to assist in earlier diagnosis, including seizures, catatonia, autonomic instability, or hyperkinesia. Indeed, reanalyzing the whole cohort using these “red flags” led to a 58% reduction of time between symptom onset and

  11. Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with hypertrophic cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Schirdewan, A.; Gapelyuk, A.; Fischer, R.; Koch, L.; Schütt, H.; Zacharzowsky, U.; Dietz, R.; Thierfelder, L.; Wessel, N.

    2007-03-01

    Hypertrophic cardiomyopathy (HCM) is a common primary inherited cardiac muscle disorder, defined clinically by the presence of unexplained left ventricular hypertrophy. The detection of affected patients remains challenging. Genetic testing is limited because only in 50%-60% of all HCM diagnoses an underlying mutation can be found. Furthermore, the disease has a varied clinical course and outcome, with many patients having little or no discernible cardiovascular symptoms, whereas others develop profound exercise limitation and recurrent arrhythmias or sudden cardiac death. Therefore prospective screening of HCM family members is strongly recommended. According to the current guidelines this includes serial echocardiographic and electrocardiographic examinations. In this study we investigated the capability of cardiac magnetic field mapping (CMFM) to detect patients suffering from HCM. We introduce for the first time a combined diagnostic approach based on map topology quantification using Kullback-Leibler (KL) entropy and regional magnetic field strength parameters. The cardiac magnetic field was recorded over the anterior chest wall using a multichannel-LT-SQUID system. CMFM was calculated based on a regular 36 point grid. We analyzed CMFM in patients with confirmed diagnosis of HCM (HCM, n =33, 43.8±13 years, 13 women, 20 men), a control group of healthy subjects (NORMAL, n =57, 39.6±8.9 years; 22 women and 35 men), and patients with confirmed cardiac hypertrophy due to arterial hypertension (HYP, n =42, 49.7±7.9 years, 15 women and 27 men). A subgroup analysis was performed between HCM patients suffering from the obstructive (HOCM, n =19) and nonobstructive (HNCM, n =14) form of the disease. KL entropy based map topology quantification alone identified HCM patients with a sensitivity of 78.8% and specificity of 86.9% (overall classification rate 84.8%). The combination of the KL parameters with a regional field strength parameter improved the overall

  12. Name Recognition to Identify Patients of South Asian Ethnicity within the Cancer Registry

    PubMed Central

    Singh-Carlson, Savitri; Wong, Frances; Oshan, Gurpreet; Lail, Harajit

    2016-01-01

    Objective: The goal of this project was to develop a list of forenames and surnames of South Asian (SA) women that could be used to identify SA breast cancer patients within the cancer registry. This list was compiled, evaluated, and validated to ensure comprehensiveness, accuracy, and applicability of SA names. Methods: This project was conducted by Canadian researchers who are immersed in conducting behavioral studies with SA women diagnosed with cancer in the province of British Columbia. Recruiting SA cancer patients for research can be a difficult task due to social and cultural factors. Methods used by other researchers to identify ethnicity related unique names were employed to filter surnames and forenames that were not common to this ethnic group. Co-author (Gurpreet Oshan) of SA ethnicity rigorously identified and deleted multiple lists and redundant entries along with common English forenames which resulted in a list of 16,888 SA forenames. All co-authors of Indian ethnicity (Gurpreet Oshan, Savitri Singh-Carlson, Harajit Lail) were involved in critiquing and manually reviewing the names list throughout this process. Comprehensive lists of SA surnames and women's forenames were reviewed to identify those that were unique to SA ethnicity. Accuracy was ensured by constantly filtering the redundancy by using an Excel program which helped to illustrate the number of times each name was spelled in different ways. Results: The final lists included 9112 surnames and 16,888 forenames of SA ethnicity. On the basis of the surname linkage only, the sensitivity of the list was 76.6%, specificity was 62.9%, and the positive predictive value was 58.5%. On the basis of both the surname and forename linkage, the specificity of the list was 88.6%. These lists include variations in spelling forenames and surnames as well. Conclusions: The list of surnames and forenames can be useful tools to identify SA ethnic groups from large population database in healthcare

  13. Experiences of patients identifying with chronic Lyme disease in the healthcare system: a qualitative study

    PubMed Central

    2014-01-01

    Background Chronic Lyme disease is a term that describes a constellation of persistent symptoms in patients with or without evidence of previous Borrelia burgdorferi infection. Patients labeled as having chronic Lyme disease have a substantial clinical burden. Little is known about chronic Lyme disease patient experiences in the healthcare system and their relationships with healthcare providers. The purpose of this study was to gather insights about the experiences of patients who carry a diagnosis of chronic Lyme disease in the United States healthcare system. Methods Qualitative, phenomenological study in 12 adult participants who identified themselves as having chronic Lyme disease. Semi-structured face-to-face in-depth interviews were conducted, 60–90 minutes in length, focusing on perceptions of disease burden and of their healthcare providers, using the dimensions of the Health Belief Model. Transcribed interviews were analyzed for emergent topics and themes in the categories of beliefs/understanding, personal history/narrative, consequences/limitations, management, and influences on care. Results Enrollment continued until theoretical saturation was obtained. Four major themes emerged from participants’ descriptions of their experiences and perceptions: 1) changes in health status and the social impact of chronic Lyme disease, 2) doubts about recovery and the future, 3) contrasting doctor-patient relationships, 4) and the use of unconventional therapies to treat chronic Lyme disease. Conclusions Participants reported a significant decline in health status associated with chronic Lyme disease and were often unsatisfied with care in conventional settings. Negative experiences were associated with reports of dismissive, patronizing, and condescending attitudes. Positive experiences were associated with providers who were reported to be attentive, optimistic, and supportive. Consultations with CAM practitioners and use of CAM therapies were common. Actively

  14. Identifying and assessing the risk of opioid abuse in patients with cancer: an integrative review

    PubMed Central

    Carmichael, Ashley-Nicole; Morgan, Laura; Del Fabbro, Egidio

    2016-01-01

    Background The misuse and abuse of opioid medications in many developed nations is a health crisis, leading to increased health-system utilization, emergency department visits, and overdose deaths. There are also increasing concerns about opioid abuse and diversion in patients with cancer, even at the end of life. Aims To evaluate the current literature on opioid misuse and abuse, and more specifically the identification and assessment of opioid-abuse risk in patients with cancer. Our secondary aim is to offer the most current evidence of best clinical practice and suggest future directions for research. Materials and methods Our integrative review included a literature search using the key terms “identification and assessment of opioid abuse in cancer”, “advanced cancer and opioid abuse”, “hospice and opioid abuse”, and “palliative care and opioid abuse”. PubMed, PsycInfo, and Embase were supplemented by a manual search. Results We found 691 articles and eliminated 657, because they were predominantly non cancer populations or specifically excluded cancer patients. A total of 34 articles met our criteria, including case studies, case series, retrospective observational studies, and narrative reviews. The studies were categorized into screening questionnaires for opioid abuse or alcohol, urine drug screens to identify opioid misuse or abuse, prescription drug-monitoring programs, and the use of universal precautions. Conclusion Screening questionnaires and urine drug screens indicated at least one in five patients with cancer may be at risk of opioid-use disorder. Several studies demonstrated associations between high-risk patients and clinical outcomes, such as aberrant behavior, prolonged opioid use, higher morphine-equivalent daily dose, greater health care utilization, and symptom burden. PMID:27330340

  15. Evaluating markers of epithelial-mesenchymal transition to identify cancer patients at risk for metastatic disease

    PubMed Central

    Busch, Evan L.; Keku, Temitope O.; Richardson, David B.; Cohen, Stephanie M.; Eberhard, David A.; Avery, Christy L.; Sandler, Robert S.

    2015-01-01

    Most cancer deaths are due to metastases. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells could be helpful to assess patient risk of metastatic disease, even among those otherwise diagnosed with local disease. Previous studies of EMT markers and patient outcomes used inconsistent methods and did not compare the clinical impact of different expression cut points for the same marker. Using digital image analysis, we measured the EMT markers Snail and E-cadherin in primary tumor specimens from 190 subjects in tissue microarrays from a population-based prospective cohort of colorectal cancer patients and estimated their associations with time-to-death. After measuring continuous marker expression data, we performed a systematic search for the cut point for each marker with the best model fit between dichotomous marker expression and time-to-death. We also assessed the potential clinical impact of different cut points for the same marker. After dichotomizing expression status at the statistically-optimal cut point, we found that Snail expression was not associated with time-to-death. When measured as a weighted average of tumor cores, low E-cadherin expression was associated with a greater risk of dying within 5 years of surgery than high expression (risk difference = 33 %, 95 % confidence interval 3–62 %). Identifying a clinically-optimal cut point for an EMT marker requires trade-offs between strength and precision of the association with patient outcomes, as well as consideration of the number of patients whose treatments might change based on using the marker at a given cut point. PMID:26507436

  16. Using text-mining techniques in electronic patient records to identify ADRs from medicine use.

    PubMed

    Warrer, Pernille; Hansen, Ebba Holme; Juhl-Jensen, Lars; Aagaard, Lise

    2012-05-01

    This literature review included studies that use text-mining techniques in narrative documents stored in electronic patient records (EPRs) to investigate ADRs. We searched PubMed, Embase, Web of Science and International Pharmaceutical Abstracts without restrictions from origin until July 2011. We included empirically based studies on text mining of electronic patient records (EPRs) that focused on detecting ADRs, excluding those that investigated adverse events not related to medicine use. We extracted information on study populations, EPR data sources, frequencies and types of the identified ADRs, medicines associated with ADRs, text-mining algorithms used and their performance. Seven studies, all from the United States, were eligible for inclusion in the review. Studies were published from 2001, the majority between 2009 and 2010. Text-mining techniques varied over time from simple free text searching of outpatient visit notes and inpatient discharge summaries to more advanced techniques involving natural language processing (NLP) of inpatient discharge summaries. Performance appeared to increase with the use of NLP, although many ADRs were still missed. Due to differences in study design and populations, various types of ADRs were identified and thus we could not make comparisons across studies. The review underscores the feasibility and potential of text mining to investigate narrative documents in EPRs for ADRs. However, more empirical studies are needed to evaluate whether text mining of EPRs can be used systematically to collect new information about ADRs.

  17. A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

    PubMed Central

    Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

    2015-01-01

    Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

  18. Cortical porosity not superior to conventional densitometry in identifying hemodialysis patients with fragility fracture

    PubMed Central

    Patsch, Janina M.; Fischer, Lukas; Bojic, Marija; Winnicki, Wolfgang; Weber, Michael; Cejka, Daniel

    2017-01-01

    Hemodialysis (HD) patients face increased fracture risk, which is further associated with elevated risk of hospitalization and mortality. High-resolution peripheral computed tomography (HR-pQCT) has advanced our understanding of bone disease in chronic kidney disease by characterizing distinct changes in both the cortical and trabecular compartments. Increased cortical porosity (Ct.Po) has been shown to be associated with fracture in patients with osteopenia or in postmenopausal diabetic women. We tested whether the degree of Ct.Po identifies hemodialysis patients with prevalent fragility fractures in comparison to bone mineral density (BMD) assessed by dual X-ray absorptiometry (DXA). We performed a post-hoc analysis of a cross-sectional study in 76 prevalent hemodialysis patients. Markers of mineral metabolism, coronary calcification score, DXA-, and HR-pQCT-data were analyzed, and Ct.Po determined at radius and tibia. Ct.Po was significantly higher in patients with fracture but association was lost after adjusting for age and gender (tibia p = 0.228, radius p = 0.5). Instead, femoral (F) BMD neck area (p = 0.03), F T-score neck area (p = 0.03), radius (R) BMD (p = 0.03), R T-score (p = 0.03), and cortical HR-pQCT indices such as cortical area (Ct.Ar) (tibia: p = 0.01; radius: p = 0.02) and cortical thickness (Ct.Th) (tibia: p = 0.03; radius: p = 0.02) correctly classified patients with fragility fractures. Area under receiver operating characteristic curves (AUC) for Ct.Po (tibia AUC: 0.711; p = 0.01; radius AUC: 0.666; p = 0.04), Ct.Ar (tibia AUC: 0.832; p<0.001; radius AUC: 0.796; p<0.001), and F neck BMD (AUC: 0.758; p = 0.002) did not differ significantly among each other. In conclusion, measuring Ct.Po is not superior to BMD determined by DXA for identification of HD patients with fragility fracture. PMID:28199411

  19. Diagnostic difficulty identifying Apophysomyces trapeziformis septic arthritis in a patient with multiple myeloma

    PubMed Central

    Schell, Wiley A.; Joyce, Maria; Alley, Christopher; Woods, Christopher W.

    2016-01-01

    Introduction: Mucormycosis is a rare fungal infection, but can cause substantial morbidity and mortality in both immunocompromised and immunocompetent patients. Apophysomyces is a mucormycetes species ubiquitous in nature, particularly in soil, decaying wood and other organic matter. Apophysomyces is known to cause cutaneous fungal infections, particularly after penetrating trauma. Septic arthritis is a rare clinical manifestation. Case presentation: We describe a case of Apophysomyces trapeziformis causing septic arthritis of the knee of a patient with multiple myeloma. He was treated multiple times for bacterial septic arthritis with minimal improvement. Surgical tissue specimens finally grew mucoraceous mould, and DNA sequencing and morphological assessment of spores identified the mould as A. trapeziformis. The patient was treated with amphotericin B and posaconazole, but ultimately required an above-the-knee amputation for definitive treatment. Conclusion: This case illustrates the need to evaluate for fungal infection in a persistent septic arthritis that is culture negative and refractory to empiric antibiotics, particularly in an immunocompromised individual. It also shows the importance of a thorough social history and adequate tissue specimens for culture. PMID:28348796

  20. Can we identify patients at risk of life-threatening allergic reactions to food?

    PubMed

    Turner, P J; Baumert, J L; Beyer, K; Boyle, R J; Chan, C-H; Clark, A T; Crevel, R W R; DunnGalvin, A; Fernández-Rivas, M; Gowland, M H; Grabenhenrich, L; Hardy, S; Houben, G F; O'B Hourihane, J; Muraro, A; Poulsen, L K; Pyrz, K; Remington, B C; Schnadt, S; van Ree, R; Venter, C; Worm, M; Mills, E N C; Roberts, G; Ballmer-Weber, B K

    2016-09-01

    Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

  1. Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

    PubMed

    Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

    2015-01-01

    Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

  2. Electronic Health Record Based Algorithm to Identify Patients with Autism Spectrum Disorder

    PubMed Central

    Chen, Pei; Bochenek, Joseph; Doshi-Velez, Finale; Manning-Courtney, Patty; Bickel, Julie; Wildenger Welchons, Leah; Reinhold, Judy; Bing, Nicole; Ni, Yizhao; Barbaresi, William; Mentch, Frank; Basford, Melissa; Denny, Joshua; Vazquez, Lyam; Perry, Cassandra; Namjou, Bahram; Qiu, Haijun; Connolly, John; Abrams, Debra; Holm, Ingrid A.; Cobb, Beth A.; Lingren, Nataline; Solti, Imre; Hakonarson, Hakon; Kohane, Isaac S.; Harley, John; Savova, Guergana

    2016-01-01

    Objective Cohort selection is challenging for large-scale electronic health record (EHR) analyses, as International Classification of Diseases 9th edition (ICD-9) diagnostic codes are notoriously unreliable disease predictors. Our objective was to develop, evaluate, and validate an automated algorithm for determining an Autism Spectrum Disorder (ASD) patient cohort from EHR. We demonstrate its utility via the largest investigation to date of the co-occurrence patterns of medical comorbidities in ASD. Methods We extracted ICD-9 codes and concepts derived from the clinical notes. A gold standard patient set was labeled by clinicians at Boston Children’s Hospital (BCH) (N = 150) and Cincinnati Children’s Hospital and Medical Center (CCHMC) (N = 152). Two algorithms were created: (1) rule-based implementing the ASD criteria from Diagnostic and Statistical Manual of Mental Diseases 4th edition, (2) predictive classifier. The positive predictive values (PPV) achieved by these algorithms were compared to an ICD-9 code baseline. We clustered the patients based on grouped ICD-9 codes and evaluated subgroups. Results The rule-based algorithm produced the best PPV: (a) BCH: 0.885 vs. 0.273 (baseline); (b) CCHMC: 0.840 vs. 0.645 (baseline); (c) combined: 0.864 vs. 0.460 (baseline). A validation at Children’s Hospital of Philadelphia yielded 0.848 (PPV). Clustering analyses of comorbidities on the three-site large cohort (N = 20,658 ASD patients) identified psychiatric, developmental, and seizure disorder clusters. Conclusions In a large cross-institutional cohort, co-occurrence patterns of comorbidities in ASDs provide further hypothetical evidence for distinct courses in ASD. The proposed automated algorithms for cohort selection open avenues for other large-scale EHR studies and individualized treatment of ASD. PMID:27472449

  3. Identifying Patient Door-to-Room Goals to Minimize Left-Without-Being-Seen Rates

    PubMed Central

    Pielsticker, Shea; Whelan, Lori; Arthur, Annette O.; Thomas, Stephen

    2015-01-01

    Introduction Emergency department (ED) patients in the leave-without-being-seen (LWBS) group risk problems of inefficiency, medical risk, and financial loss. The goal at our hospital is to limit LWBS to <1%. This study’s goal was to assess the influence on LWBS associated with prolonging intervals between patient presentation and placement in an exam room (DoorRoom time). This study’s major aim was to identify DoorRoom cutoffs that maximize likelihood of meeting the LWBS goal (i.e. <1%). Methods We conducted the study over one year (8/13–8/14) using operations data for an ED with annual census ~50,000. For each study day, the LWBS endpoint (i.e. was LWBS <1%: “yes or no”) and the mean DoorRoom time were recorded. We categorized DoorRoom means by intervals starting with ≤10min and ending at >60min. Multivariate logistic regression was used to assess for DoorRoom cutoffs predicting high LWBS, while adjusting for patient acuity (triage scores and admission %) and operations parameters. We used predictive marginal probability to assess utility of the regression-generated cutoffs. We defined statistical significance at p<0.05 and report odds ratio (OR) and 95% confidence intervals (CI). Results Univariate results suggested a primary DoorRoom cutoff of 20′, to maintain a high likelihood (>85%) of meeting the LWBS goal. A secondary DoorRoom cutoff was indicated at 35′, to prevent a precipitous drop-off in likelihood of meeting the LWBS goal, from 61.1% at 35′ to 34.4% at 40′. Predictive marginal analysis using multivariate techniques to control for operational and patient-acuity factors confirmed the 20′ and 35′ cutoffs as significant (p<0.001). Days with DoorRoom between 21–35′ were 74% less likely to meet the LWBS goal than days with DoorRoom ≤20′ (OR 0.26, 95% CI [0.13–0.53]). Days with DoorRoom >35′ were a further 75% less likely to meet the LWBS goal than days with DoorRoom of 21–35′ (OR 0.25, 95% CI [0.15–0.41]). Conclusion

  4. Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia

    PubMed Central

    Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd

    2015-01-01

    Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients’ sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia. PMID:26039628

  5. Calibrating the High Density Magnetic Port within Tissue Expanders to Achieve more Accurate Dose Calculations for Postmastectomy Patients with Immediate Breast Reconstruction

    NASA Astrophysics Data System (ADS)

    Jones, Jasmine; Zhang, Rui; Heins, David; Castle, Katherine

    In postmastectomy radiotherapy, an increasing number of patients have tissue expanders inserted subpectorally when receiving immediate breast reconstruction. These tissue expanders are composed of silicone and are inflated with saline through an internal metallic port; this serves the purpose of stretching the muscle and skin tissue over time, in order to house a permanent implant. The issue with administering radiation therapy in the presence of a tissue expander is that the port's magnetic core can potentially perturb the dose delivered to the Planning Target Volume, causing significant artifacts in CT images. Several studies have explored this problem, and suggest that density corrections must be accounted for in treatment planning. However, very few studies accurately calibrated commercial TP systems for the high density material used in the port, and no studies employed fusion imaging to yield a more accurate contour of the port in treatment planning. We compared depth dose values in the water phantom between measurement and TPS calculations, and we were able to overcome some of the inhomogeneities presented by the image artifact by fusing the KVCT and MVCT images of the tissue expander together, resulting in a more precise comparison of dose calculations at discrete locations. We expect this method to be pivotal in the quantification of dose distribution in the PTV. Research funded by the LS-AMP Award.

  6. A New Accurate 3D Measurement Tool to Assess the Range of Motion of the Tongue in Oral Cancer Patients: A Standardized Model.

    PubMed

    van Dijk, Simone; van Alphen, Maarten J A; Jacobi, Irene; Smeele, Ludwig E; van der Heijden, Ferdinand; Balm, Alfons J M

    2016-02-01

    In oral cancer treatment, function loss such as speech and swallowing deterioration can be severe, mostly due to reduced lingual mobility. Until now, there is no standardized measurement tool for tongue mobility and pre-operative prediction of function loss is based on expert opinion instead of evidence based insight. The purpose of this study was to assess the reliability of a triple-camera setup for the measurement of tongue range of motion (ROM) in healthy adults and its feasibility in patients with partial glossectomy. A triple-camera setup was used, and 3D coordinates of the tongue in five standardized tongue positions were achieved in 15 healthy volunteers. Maximum distances between the tip of the tongue and the maxillary midline were calculated. Each participant was recorded twice, and each movie was analysed three times by two separate raters. Intrarater, interrater and test-retest reliability were the main outcome measures. Secondly, feasibility of the method was tested in ten patients treated for oral tongue carcinoma. Intrarater, interrater and test-retest reliability all showed high correlation coefficients of >0.9 in both study groups. All healthy subjects showed perfect symmetrical tongue ROM. In patients, significant differences in lateral tongue movements were found, due to restricted tongue mobility after surgery. This triple-camera setup is a reliable measurement tool to assess three-dimensional information of tongue ROM. It constitutes an accurate tool for objective grading of reduced tongue mobility after partial glossectomy.

  7. Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

    PubMed Central

    2017-01-01

    Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

  8. Differential DNA methylation identified in the blood and retina of AMD patients.

    PubMed

    Oliver, Verity F; Jaffe, Andrew E; Song, Jin; Wang, Guohua; Zhang, Pingwu; Branham, Kari E; Swaroop, Anand; Eberhart, Charles G; Zack, Donald J; Qian, Jiang; Merbs, Shannath L

    2015-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWAS-defined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression.

  9. Differential DNA methylation identified in the blood and retina of AMD patients

    PubMed Central

    Oliver, Verity F; Jaffe, Andrew E; Song, Jin; Wang, Guohua; Zhang, Pingwu; Branham, Kari E; Swaroop, Anand; Eberhart, Charles G; Zack, Donald J; Qian, Jiang; Merbs, Shannath L

    2015-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWAS-defined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression. PMID:26067391

  10. Identifying the tooth shade in group of patients using Vita Easyshade

    PubMed Central

    Elamin, Habab Osman; Abubakr, Neamat Hassan; Ibrahim, Yahia Eltayib

    2015-01-01

    Objective: The aim of the present investigation is to identify tooth shade among a group of Sudanese patients. Materials and Methods: Total number of patients was 227. Participant's age ranged from 15 to 72 years, which, was divided into four groups. The tooth included in the study was either right or left sounds maxillary central incisor. Vita Easyshade was used to select the tooth shade. Investigation of the differences of Commission International de l’Eclairage (CIELab) coordinates among gender and state of origin was conducted together with an examination of the relationship between CIELab coordinates and age. One-way analysis of variance was used to test the differences in L*, a* and b* according to state of origin. Results: Results showed that A3 was the most common classical tooth shade respectively. There was highly significant difference in L* between males and females (P = 0.002). There was a significant relation between tooth shade and age (P = 0.026). There was a high significant association between classical tooth shade and Sudan regions (P = 0.00). Conclusion: In conclusion, most common classical shade was A3, women's teeth were lighter than men's. There was a relation between ethnic background and tooth shade. PMID:26038652

  11. Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal dialysis patients

    PubMed Central

    Ruiz-Carpio, Vicente; Sandoval, Pilar; Aguilera, Abelardo; Albar-Vizcaíno, Patricia; Perez-Lozano, María Luisa; González-Mateo, Guadalupe T.; Acuña-Ruiz, Adrián; García-Cantalejo, Jesús; Botías, Pedro; Bajo, María Auxiliadora; Selgas, Rafael; Sánchez-Tomero, José Antonio; Passlick-Deetjen, Jutta; Piecha, Dorothea; Büchel, Janine; Steppan, Sonja; López-Cabrera, Manuel

    2017-01-01

    Peritoneal dialysis (PD) is an effective renal replacement therapy, but a significant proportion of patients suffer PD-related complications, which limit the treatment duration. Mesothelial-to-mesenchymal transition (MMT) contributes to the PD-related peritoneal dysfunction. We analyzed the genetic reprograming of MMT to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping between MMT induced in vitro and ex vivo in effluent-derived mesothelial cells, and that MMT is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. Cellular morphology and number of altered genes showed that MMT ex vivo could be subdivided into two stages: early/epithelioid and advanced/non-epithelioid. RT-PCR array analysis demonstrated that a number of genes differentially expressed in effluent-derived non-epithelioid cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were measured in PD effluents, and except GREM1, showed significant differences between early and advanced stages of MMT, and their expression was associated with a high peritoneal transport status. The results establish a proof of concept about the feasibility of measuring MMT-associated secreted protein levels as potential biomarkers in PD. PMID:28327551

  12. Atrial Fibrillation Identified During Echocardiography in a Patient with Recurrent Cardioembolic Events: A Case Report

    PubMed Central

    Christia, Panagiota; Katsa, Ioanna; Ocava, Lenore; Faillace, Robert

    2016-01-01

    Patient: Female, 80 Final Diagnosis: Stroke Symptoms: Weakness • left sided Medication: — Clinical Procedure: Echocardiogram Specialty: Naurology Objective: Unusual clinical course Background: Stroke is the major cause of disability and the fifth leading cause of death in the United States. In 30–40% of strokes the etiology remains uncertain or unknown. Identifying the cause of a cerebrovascular event offers the opportunity for an intervention that may decrease the risk of future stroke and thus prevent the resultant impairment. Case Report: We report the case of an 80-year-old African American woman with a prior right middle cerebral artery stroke, who presented to the hospital with new left-sided weakness and was found to have a new right-sided frontal lobe infarct. Twenty-four hour Holter monitoring performed during this hospitalization and prior 24-h electrocardiogram (ECG) recording did not reveal an arrhythmia. However, the patient was found to have an isolated episode of atrial fibrillation (AF) during an echocardiogram as part of the evaluation for stroke etiology. Conclusions: AF is an important and treatable cause of recurrent stroke and needs to be ruled out by thorough evaluation before the diagnosis of cryptogenic stroke is assigned. Despite meticulous diagnostic work-up, many strokes caused by paroxysmal AF remain undetected and longer ECG monitoring (>24 h) may be required. PMID:26932564

  13. Genomic reprograming analysis of the Mesothelial to Mesenchymal Transition identifies biomarkers in peritoneal dialysis patients.

    PubMed

    Ruiz-Carpio, Vicente; Sandoval, Pilar; Aguilera, Abelardo; Albar-Vizcaíno, Patricia; Perez-Lozano, María Luisa; González-Mateo, Guadalupe T; Acuña-Ruiz, Adrián; García-Cantalejo, Jesús; Botías, Pedro; Bajo, María Auxiliadora; Selgas, Rafael; Sánchez-Tomero, José Antonio; Passlick-Deetjen, Jutta; Piecha, Dorothea; Büchel, Janine; Steppan, Sonja; López-Cabrera, Manuel

    2017-03-22

    Peritoneal dialysis (PD) is an effective renal replacement therapy, but a significant proportion of patients suffer PD-related complications, which limit the treatment duration. Mesothelial-to-mesenchymal transition (MMT) contributes to the PD-related peritoneal dysfunction. We analyzed the genetic reprograming of MMT to identify new biomarkers that may be tested in PD-patients. Microarray analysis revealed a partial overlapping between MMT induced in vitro and ex vivo in effluent-derived mesothelial cells, and that MMT is mainly a repression process being higher the number of genes that are down-regulated than those that are induced. Cellular morphology and number of altered genes showed that MMT ex vivo could be subdivided into two stages: early/epithelioid and advanced/non-epithelioid. RT-PCR array analysis demonstrated that a number of genes differentially expressed in effluent-derived non-epithelioid cells also showed significant differential expression when comparing standard versus low-GDP PD fluids. Thrombospondin-1 (TSP1), collagen-13 (COL13), vascular endothelial growth factor A (VEGFA), and gremlin-1 (GREM1) were measured in PD effluents, and except GREM1, showed significant differences between early and advanced stages of MMT, and their expression was associated with a high peritoneal transport status. The results establish a proof of concept about the feasibility of measuring MMT-associated secreted protein levels as potential biomarkers in PD.

  14. Novel PTPRQ mutations identified in three congenital hearing loss patients with various types of hearing loss

    PubMed Central

    Sakuma, Naoko; Moteki, Hideaki; Azaiez, Hela; Booth, Kevin T; Takahashi, Masahiro; Arai, Yasuhiro; Shearer, A Eliot; Sloan, Christina M; Nishio, Shin-ya; Kolbe, Diana L; Iwasaki, Satoshi; Oridate, Nobuhiko; Smith, Richard J H; Usami, Shin-ichi

    2015-01-01

    Objective We present three patients with congenital sensorineural hearing loss (SNHL) caused by the novel PTPRQ mutations, including clinical manifestations and phenotypic features. Methods Two hundred and twenty (220) Japanese subjects with sensorineural hearing loss from unrelated and non-consanguineous families were enrolled in the study. Targeted genomic enrichment with massively parallel sequencing of all known non-syndromic hearing loss genes was performed to identify the genetic cause of hearing loss. Results Four novel causative PTPRQ mutations were identified in three cases. Case 1 had progressive profound SNHL with homozygous nonsense mutation. Case 2 had non-progressive profound SNHL with compound heterozygous mutation (nonsense and missense mutation). Case 3 had non-progressive moderate SNHL with compound heterozygous mutation (missense and splice site mutation). Caloric test and vestibular evoked myogenic potential (VEMP) test showed vestibular dysfunction in Case 1. Conclusion Hearing loss levels and progression among the present cases were varied, and there seem to be no obvious correlation between genotypes and the phenotypic features of their hearing loss. The PTPRQ mutation appeared to be responsible for the vestibular dysfunction. PMID:25788564

  15. Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis.

    PubMed

    Goldberg, David S; Taddei, Tamar H; Serper, Marina; Mehta, Rajni; Dieperink, Eric; Aytaman, Ayse; Baytarian, Michelle; Fox, Rena; Hunt, Kristel; Pedrosa, Marcos; Pocha, Christine; Valderrama, Adriana; Kaplan, David E

    2017-03-01

    Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest-risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver-related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up-to-date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow-up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72-0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85-0.94 if lead time 91-180 days.

  16. “Impactibility Models”: Identifying the Subgroup of High-Risk Patients Most Amenable to Hospital-Avoidance Programs

    PubMed Central

    Lewis, Geraint H

    2010-01-01

    Context: Predictive models can be used to identify people at high risk of unplanned hospitalization, although some of the high-risk patients they identify may not be amenable to preventive care. This study describes the development of “impactibility models,” which aim to identify the subset of at-risk patients for whom preventive care is expected to be successful. Methods: This research used semistructured interviews with representatives of thirty American organizations that build, use, or appraise predictive models for health care. Findings: Impactibility models may refine the output of predictive models by (1) giving priority to patients with diseases that are particularly amenable to preventive care; (2) excluding patients who are least likely to respond to preventive care; or (3) identifying the form of preventive care best matched to each patient's characteristics. Conclusions: Impactibility models could improve the efficiency of hospital-avoidance programs, but they have important implications for equity and access. PMID:20579284

  17. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment.

    PubMed

    Chételat, Gaël; Eustache, Francis; Viader, Fausto; De La Sayette, Vincent; Pélerin, Alice; Mézenge, Florence; Hannequin, Didier; Dupuy, Benoît; Baron, Jean-Claude; Desgranges, Béatrice

    2005-02-01

    The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage

  18. Novel Carboxypeptidase A6 (CPA6) Mutations Identified in Patients with Juvenile Myoclonic and Generalized Epilepsy

    PubMed Central

    Sapio, Matthew R.; Vessaz, Monique; Thomas, Pierre; Genton, Pierre; Fricker, Lloyd D.; Salzmann, Annick

    2015-01-01

    Carboxypeptidase A6 (CPA6) is a peptidase that removes C-terminal hydrophobic amino acids from peptides and proteins. The CPA6 gene is expressed in the brains of humans and animals, with high levels of expression during development. It is translated with a prodomain (as proCPA6), which is removed before secretion. The active form of CPA6 binds tightly to the extracellular matrix (ECM) where it is thought to function in the processing of peptides and proteins. Mutations in the CPA6 gene have been identified in patients with temporal lobe epilepsy and febrile seizures. In the present study, we screened for CPA6 mutations in patients with juvenile myoclonic epilepsy and identified two novel missense mutations: Arg36His and Asn271Ser. Patients harboring these mutations also presented with generalized epilepsy. Neither of the novel mutations was found in a control population. Asn271 is highly conserved in CPA6 and other related metallocarboxypeptidases. Arg36 is present in the prodomain and is not highly conserved. To assess structural consequences of the amino acid substitutions, both mutants were modeled within the predicted structure of the enzyme. To examine the effects of these mutations on enzyme expression and activity, we expressed the mutated enzymes in human embryonic kidney 293T cells. These analyses revealed that Asn271Ser abolished enzymatic activity, while Arg36His led to a ~50% reduction in CPA6 levels in the ECM. Pulse-chase using radio-labeled amino acids was performed to follow secretion. Newly-synthesized CPA6 appeared in the ECM with peak levels between 2-8 hours. There was no major difference in time course between wild-type and mutant forms, although the amount of radiolabeled CPA6 in the ECM was lower for the mutants. Our experiments demonstrate that these mutations in CPA6 are deleterious and provide further evidence for the involvement of CPA6 mutations in the predisposition for several types of epilepsy. PMID:25875328

  19. SNP-array based whole genome homozygosity mapping: a quick and powerful tool to achieve an accurate diagnosis in LGMD2 patients.

    PubMed

    Papić, Lea; Fischer, Dirk; Trajanoski, Slave; Höftberger, Romana; Fischer, Carina; Ströbel, Thomas; Schmidt, Wolfgang M; Bittner, Reginald E; Schabhüttl, Maria; Gruber, Karin; Pieber, Thomas R; Janecke, Andreas R; Auer-Grumbach, Michaela

    2011-01-01

    A large number of novel disease genes have been identified by homozygosity mapping and the positional candidate approach. In this study we used single nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both affected siblings showed homozygous blocks on chromosome 15 corresponding to the LGMD2A locus. Direct sequencing of CAPN3, encoding calpain-3, identified a homozygous deletion c.483delG (p.Ile162SerfsX17). In a sporadic LGMD patient complete absence of caveolin-3 on Western blot was observed. However, a mutation in CAV3 could not be detected. Homozygosity mapping revealed a large homozygous block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related-protein detected the common homozygous c.826 C>A (p.Leu276Ile) mutation. Subsequent re-examination of this patient's muscle biopsy showed aberrant α-dystroglycan glycosylation. In summary, we show that whole-genome homozygosity mapping using low cost SNP arrays provides a fast and non-invasive method to identify disease-causing mutations in sporadic patients or sibs from consanguineous families in LGMD2. Furthermore, this is the first study describing that in addition to PTRF, encoding polymerase I and transcript release factor, FKRP mutations may cause secondary caveolin-3 deficiency.

  20. Summary Report on the Graded Prognostic Assessment: An Accurate and Facile Diagnosis-Specific Tool to Estimate Survival for Patients With Brain Metastases

    PubMed Central

    Sperduto, Paul W.; Kased, Norbert; Roberge, David; Xu, Zhiyuan; Shanley, Ryan; Luo, Xianghua; Sneed, Penny K.; Chao, Samuel T.; Weil, Robert J.; Suh, John; Bhatt, Amit; Jensen, Ashley W.; Brown, Paul D.; Shih, Helen A.; Kirkpatrick, John; Gaspar, Laurie E.; Fiveash, John B.; Chiang, Veronica; Knisely, Jonathan P.S.; Sperduto, Christina Maria; Lin, Nancy; Mehta, Minesh

    2012-01-01

    Purpose Our group has previously published the Graded Prognostic Assessment (GPA), a prognostic index for patients with brain metastases. Updates have been published with refinements to create diagnosis-specific Graded Prognostic Assessment indices. The purpose of this report is to present the updated diagnosis-specific GPA indices in a single, unified, user-friendly report to allow ease of access and use by treating physicians. Methods A multi-institutional retrospective (1985 to 2007) database of 3,940 patients with newly diagnosed brain metastases underwent univariate and multivariate analyses of prognostic factors associated with outcomes by primary site and treatment. Significant prognostic factors were used to define the diagnosis-specific GPA prognostic indices. A GPA of 4.0 correlates with the best prognosis, whereas a GPA of 0.0 corresponds with the worst prognosis. Results Significant prognostic factors varied by diagnosis. For lung cancer, prognostic factors were Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases, confirming the original Lung-GPA. For melanoma and renal cell cancer, prognostic factors were Karnofsky performance score and the number of brain metastases. For breast cancer, prognostic factors were tumor subtype, Karnofsky performance score, and age. For GI cancer, the only prognostic factor was the Karnofsky performance score. The median survival times by GPA score and diagnosis were determined. Conclusion Prognostic factors for patients with brain metastases vary by diagnosis, and for each diagnosis, a robust separation into different GPA scores was discerned, implying considerable heterogeneity in outcome, even within a single tumor type. In summary, these indices and related worksheet provide an accurate and facile diagnosis-specific tool to estimate survival, potentially select appropriate treatment, and stratify clinical trials for patients with brain metastases. PMID:22203767

  1. TU-EF-204-01: Accurate Prediction of CT Tube Current Modulation: Estimating Tube Current Modulation Schemes for Voxelized Patient Models Used in Monte Carlo Simulations

    SciTech Connect

    McMillan, K; Bostani, M; McNitt-Gray, M; McCollough, C

    2015-06-15

    Purpose: Most patient models used in Monte Carlo-based estimates of CT dose, including computational phantoms, do not have tube current modulation (TCM) data associated with them. While not a problem for fixed tube current simulations, this is a limitation when modeling the effects of TCM. Therefore, the purpose of this work was to develop and validate methods to estimate TCM schemes for any voxelized patient model. Methods: For 10 patients who received clinically-indicated chest (n=5) and abdomen/pelvis (n=5) scans on a Siemens CT scanner, both CT localizer radiograph (“topogram”) and image data were collected. Methods were devised to estimate the complete x-y-z TCM scheme using patient attenuation data: (a) available in the Siemens CT localizer radiograph/topogram itself (“actual-topo”) and (b) from a simulated topogram (“sim-topo”) derived from a projection of the image data. For comparison, the actual TCM scheme was extracted from the projection data of each patient. For validation, Monte Carlo simulations were performed using each TCM scheme to estimate dose to the lungs (chest scans) and liver (abdomen/pelvis scans). Organ doses from simulations using the actual TCM were compared to those using each of the estimated TCM methods (“actual-topo” and “sim-topo”). Results: For chest scans, the average differences between doses estimated using actual TCM schemes and estimated TCM schemes (“actual-topo” and “sim-topo”) were 3.70% and 4.98%, respectively. For abdomen/pelvis scans, the average differences were 5.55% and 6.97%, respectively. Conclusion: Strong agreement between doses estimated using actual and estimated TCM schemes validates the methods for simulating Siemens topograms and converting attenuation data into TCM schemes. This indicates that the methods developed in this work can be used to accurately estimate TCM schemes for any patient model or computational phantom, whether a CT localizer radiograph is available or not

  2. Identifying Areas of the Visual Field Important for Quality of Life in Patients with Glaucoma

    PubMed Central

    Murata, Hiroshi; Hirasawa, Hiroyo; Aoyama, Yuka; Sugisaki, Kenji; Araie, Makoto; Mayama, Chihiro; Aihara, Makoto; Asaoka, Ryo

    2013-01-01

    Purpose The purpose of this study was to create a vision-related quality of life (VRQoL) prediction system to identify visual field (VF) test points associated with decreased VRQoL in patients with glaucoma. Method VRQoL score was surveyed in 164 patients with glaucoma using the ‘Sumi questionnaire’. A binocular VF was created from monocular VFs by using the integrated VF (IVF) method. VRQoL score was predicted using the ‘Random Forest’ method, based on visual acuity (VA) of better and worse eyes (better-eye and worse-eye VA) and total deviation (TD) values from the IVF. For comparison, VRQoL scores were regressed (linear regression) against: (i) mean of TD (IVF MD); (ii) better-eye VA; (iii) worse-eye VA; and (iv) IVF MD and better- and worse-eye VAs. The rank of importance of IVF test points was identified using the Random Forest method. Results The root mean of squared prediction error associated with the Random Forest method (0.30 to 1.97) was significantly smaller than those with linear regression models (0.34 to 3.38, p<0.05, ten-fold cross validation test). Worse-eye VA was the most important variable in all VRQoL tasks. In general, important VF test points were concentrated along the horizontal meridian. Particular areas of the IVF were important for different tasks: peripheral superior and inferior areas in the left hemifield for the ‘letters and sentences’ task, peripheral, mid-peripheral and para-central inferior regions for the ‘walking’ task, the peripheral superior region for the ‘going out’ task, and a broad scattered area across the IVF for the ‘dining’ task. Conclusion The VRQoL prediction model with the Random Forest method enables clinicians to better understand patients’ VRQoL based on standard clinical measurements of VA and VF. PMID:23520528

  3. A longitudinal study to identify the influence of quality of chronic care delivery on productive interactions between patients and (teams of) healthcare professionals within disease management programmes

    PubMed Central

    Cramm, Jane Murray; Nieboer, Anna Petra

    2014-01-01

    Objective The chronic care model is an increasingly used approach to improve the quality of care through system changes in care delivery. While theoretically these system changes are expected to increase productive patient–professional interaction empirical evidence is lacking. This study aims to identify the influence of quality of care on productive patient–professional interaction. Setting Longitudinal study in 18 Dutch regions. Participants Questionnaires were sent to all 5076 patients participating in 18 Disease Management Programmes (DMPs) in 2010 (2676 (53%) respondents). One year later (T1), 4693 patients still participating in the DMPs received a questionnaire (2191 (47%) respondents) and 2 years later (in 2012; T2) 1722 patients responded (out of 4350; 40% response). Interventions DMPs Primary outcome measure Patients’ perceptions of the productivity of interactions (measured as relational coordination/coproduction of care) with professionals. Patients were asked about communication dimensions (frequent, accurate, and problem-solving communication) and relationship dimensions (shared goals and mutual respect). Findings After controlling for background characteristics these results clearly show that quality of chronic care (T0), first-year changes in quality of chronic care (T1—T0) and second-year changes in quality of chronic care (T2—T1) predicted productive interactions between patients and professionals at T2 (all at p≤0.001). Furthermore, we found a negative relationship between lower educational level and productive interactions between patients and professionals 2 years later. Conclusions We can conclude that successfully dealing with the consequences of chronic illnesses requires proactive patients who are able to make productive decisions together with their healthcare providers. Since patients and professionals share responsibility for management of the chronic illness, they must also share control of interactions and decisions

  4. Phase angle as bioelectrical marker to identify elderly patients at risk of sarcopenia.

    PubMed

    Basile, Claudia; Della-Morte, David; Cacciatore, Francesco; Gargiulo, Gaetano; Galizia, Gianluigi; Roselli, Mario; Curcio, Francesco; Bonaduce, Domenico; Abete, Pasquale

    2014-10-01

    Several markers have been associated with sarcopenia in the elderly, including bioelectrical indices. Phase angle (PhA) is an impedance parameter and it has been suggested as an indicator of cellular death. Thus, the relationship between PhA and muscle mass and strength was investigated in 207 consecutively elderly participants (mean age 76.2±6.7years) admitted for multidimensional geriatric evaluation. Muscle strength by grip strength using a hand-held dynamometer and muscle mass was measured by bioimpedentiometer. PhA was calculated directly with its arctangent (resistance/reactance×180°/π). Linear relationship among muscular mass and strength and with clinical and biochemical parameters, including PhA at uni- and multivariate analysis were performed. Linear regression analysis demonstrated that lower level of PhA is associated with reduction in grip strength (y=3.16+0.08x; r=0.49; p<0.001), and even more, with muscle mass (y=3.04+0.25x; r=0.60; p<0001). Multivariate analysis confirms these relationships (grip strength β=0.245, p=0.031; muscular mass β=0.623, p<0.01). Thus, PhA is inversely related to muscle mass and strength in elderly subjects and it may be considered a good bioelectrical marker to identify elderly patients at risk of sarcopenia.

  5. The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study

    PubMed Central

    Brown, Sheldon T.; Tate, Janet P.; Kyriakides, Tassos C.; Kirkwood, Katherine A.; Holodniy, Mark; Goulet, Joseph L.; Angus, Brian J.; Cameron, D. William; Justice, Amy C.

    2014-01-01

    Objectives The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study. Methods Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality. Results Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores. Conclusions The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research. PMID:24667813

  6. Identifying Patient Perceived Barriers to Trichiasis Surgery in Kongwa District, Tanzania

    PubMed Central

    Bickley, Ryan J.; Mkocha, Harran; Munoz, Beatriz

    2017-01-01

    Background Trachomatous trichiasis (TT), inturned eyelashes from repeated infection with Chlamydia trachomatis, is the leading infectious cause of blindness in the world. Though surgery will correct entropion caused by trachoma, uptake of TT surgery remains low. In this case-control study, we identify barriers that prevent TT patients from receiving sight-saving surgery. Methodology/Principal Findings Participants were selected from a database of TT cases who did (acceptors) and did not (non-acceptors) have surgery as of August 2015. We developed an in-home interview questionnaire, using open and closed-ended questions on perceived barriers to accessing surgical services. We compared responses between the acceptors and non-acceptors, examining differences in reasons for and against surgery, sources of TT information, and suggestions for improving surgical delivery. 167 participants (mean age 61 years, 79.7% females) were interviewed. Compared to acceptors, non-acceptors were more likely to report they had no one to accompany them to surgery (75.3% vs. 42.6%, p<0.0001), they could manage TT on their own (69.9% vs. 31.5%, p<0.0001), and the surgery camp was too far (53.4% vs. 28.7%, p = 0.001). Over 90% of both acceptors and non-acceptors agreed on the benefits of having surgery. Fear of surgery was the biggest barrier stated by both groups. Despite this fear, acceptors were more likely than non-acceptors to also report fear of losing further vision without surgery. Conclusions/Significance Barriers included access issues, familial and/or work responsibilities, the perception that self-management was sufficient, and lack of education about surgery. Fear of surgery was the biggest barrier facing both acceptors and non-acceptors. Increasing uptake will require addressing how surgery is presented to community residents, including outlining treatment logistics, surgical outcomes, and stressing the risk of vision loss. PMID:28052070

  7. Normalization of Patient-Identified Plasma Biomarkers in SMNΔ7 Mice following Postnatal SMN Restoration

    PubMed Central

    Arnold, W. David; Duque, Sandra; Iyer, Chitra C.; Zaworski, Phillip; McGovern, Vicki L.; Taylor, Shannon J.; von Herrmann, Katharine M.; Kobayashi, Dione T.; Chen, Karen S.; Kolb, Stephen J.; Paushkin, Sergey V.; Burghes, Arthur H. M.

    2016-01-01

    Introduction and Objective Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function. The goal was to determine whether levels of plasma markers were altered in the SMNΔ7 mouse model of SMA and whether postnatal SMN restoration resulted in normalization of the biomarkers. Methods SMNΔ7 and control mice were treated with antisense oligonucleotides (ASO) targeting ISS-N1 to increase SMN protein from SMN2 or scramble ASO (sham treatment) via intracerebroventricular injection on postnatal day 1 (P1). Brain, spinal cord, quadriceps muscle, and liver were analyzed for SMN protein levels at P12 and P90. Ten plasma biomarkers (a subset of biomarkers in the SMA-MAP panel available for analysis in mice) were analyzed in plasma obtained at P12, P30, and P90. Results Of the eight plasma biomarkers assessed, 5 were significantly changed in sham treated SMNΔ7 mice compared to control mice and were normalized in SMNΔ7 mice treated with ASO. Conclusion This study defines a subset of the SMA-MAP plasma biomarker panel that is abnormal in the most commonly used mouse model of SMA. Furthermore, some of these markers are responsive to postnatal SMN restoration. These findings support continued clinical development of these potential prognostic and pharmacodynamic biomarkers. PMID:27907033

  8. A Focus Group Exploration of Automated Case-Finders to Identify High-Risk Heart Failure Patients Within an Urban Safety Net Hospital

    PubMed Central

    Patterson, Mark E.; Miranda, Derick; Schuman, Greg; Eaton, Christopher; Smith, Andrew; Silver, Brad

    2016-01-01

    Background: Leveraging “big data” as a means of informing cost-effective care holds potential in triaging high-risk heart failure (HF) patients for interventions within hospitals seeking to reduce 30-day readmissions. Objective: Explore provider’s beliefs and perceptions about using an electronic health record (EHR)-based tool that uses unstructured clinical notes to risk-stratify high-risk heart failure patients. Methods: Six providers from an inpatient HF clinic within an urban safety net hospital were recruited to participate in a semistructured focus group. A facilitator led a discussion on the feasibility and value of using an EHR tool driven by unstructured clinical notes to help identify high-risk patients. Data collected from transcripts were analyzed using a thematic analysis that facilitated drawing conclusions clustered around categories and themes. Results: From six categories emerged two themes: (1) challenges of finding valid and accurate results, and (2) strategies used to overcome these challenges. Although employing a tool that uses electronic medical record (EMR) unstructured text as the benchmark by which to identify high-risk patients is efficient, choosing appropriate benchmark groups could be challenging given the multiple causes of readmission. Strategies to mitigate these challenges include establishing clear selection criteria to guide benchmark group composition, and quality outcome goals for the hospital. Conclusion: Prior to implementing into practice an innovative EMR-based case-finder driven by unstructured clinical notes, providers are advised to do the following: (1) define patient quality outcome goals, (2) establish criteria by which to guide benchmark selection, and (3) verify the tool’s validity and reliability. Achieving consensus on these issues would be necessary for this innovative EHR-based tool to effectively improve clinical decision-making and in turn, decrease readmissions for high-risk patients. PMID:27683666

  9. Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated with Chemotherapy with or without Immunotherapy

    PubMed Central

    Martinelli, Sara; Cuneo, Antonio; Formigaro, Luca; Cavallari, Maurizio; Lista, Enrico; Quaglia, Francesca Maria; Ciccone, Maria; Bardi, Antonella; Volta, Eleonora; Tammiso, Elisa; Saccenti, Elena; Sofritti, Olga; Daghia, Giulia; Negrini, Massimo; Dabusti, Melissa; Tomasi, Paolo; Moretti, Sabrina; Cavazzini, Francesco; Rigolin, Gian Matteo

    2016-01-01

    Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment. PMID:27872727

  10. The M. D. Anderson Symptom Inventory-Head and Neck Module, a Patient-Reported Outcome Instrument, Accurately Predicts the Severity of Radiation-Induced Mucositis

    SciTech Connect

    Rosenthal, David I. Mendoza, Tito R.; Chambers, Mark; Burkett, V. Shannon; Garden, Adam S.; Hessell, Amy C.; Lewin, Jan S.; Ang, K. Kian; Kies, Merrill S.

    2008-12-01

    Purpose: To compare the M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective. Methods and Materials: Consecutive patients with head-and-neck cancer (n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositis scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Results: The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN. Conclusion: Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN.

  11. Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome.

    PubMed

    Juang, Jyh-Ming Jimmy; Lu, Tzu-Pin; Lai, Liang-Chuan; Ho, Chia-Chuan; Liu, Yen-Bin; Tsai, Chia-Ti; Lin, Lian-Yu; Yu, Chih-Chieh; Chen, Wen-Jone; Chiang, Fu-Tien; Yeh, Shih-Fan Sherri; Lai, Ling-Ping; Chuang, Eric Y; Lin, Jiunn-Lee

    2014-10-23

    Brugada syndrome (BrS) is one of the ion channelopathies associated with sudden cardiac death (SCD). The most common BrS-associated gene (SCN5A) only accounts for approximately 20-25% of BrS patients. This study aims to identify novel mutations across human ion channels in non-familial BrS patients without SCN5A variants through disease-targeted sequencing. We performed disease-targeted multi-gene sequencing across 133 human ion channel genes and 12 reported BrS-associated genes in 15 unrelated, non-familial BrS patients without SCN5A variants. Candidate variants were validated by mass spectrometry and Sanger sequencing. Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three BrS patients (20%). Two of the three patients presented SCD and one had syncope. Interestingly, the two patients presented with SCD had compound mutations (SCNN1A:Arg350Gln and KCNB2:Glu522Lys; SCNN1A:Arg597* and KCNJ16:Ser261Gly). Importantly, two SCNN1A mutations were identified from different families. The KCNT1:Arg1106Gln mutation was identified in a patient with syncope. Bioinformatics algorithms predicted severe functional interruptions in these four mutation loci, suggesting their pivotal roles in BrS. This study identified four novel BrS-associated genes and indicated the effectiveness of this disease-targeted sequencing across ion channel genes for non-familial BrS patients without SCN5A variants.

  12. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

    PubMed Central

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-01-01

    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α3.7), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (αcodon 59α/αCSα) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (αcodon 59α/αPakséα) after nine years of being misdiagnosis with Hb Adana and HbCS (αcodon 59α/αCSα). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations. PMID:27271331

  13. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  14. Mining Clinicians' Electronic Documentation to Identify Heart Failure Patients with Ineffective Self-Management: A Pilot Text-Mining Study.

    PubMed

    Topaz, Maxim; Radhakrishnan, Kavita; Lei, Victor; Zhou, Li

    2016-01-01

    Effective self-management can decrease up to 50% of heart failure hospitalizations. Unfortunately, self-management by patients with heart failure remains poor. This pilot study aimed to explore the use of text-mining to identify heart failure patients with ineffective self-management. We first built a comprehensive self-management vocabulary based on the literature and clinical notes review. We then randomly selected 545 heart failure patients treated within Partners Healthcare hospitals (Boston, MA, USA) and conducted a regular expression search with the compiled vocabulary within 43,107 interdisciplinary clinical notes of these patients. We found that 38.2% (n = 208) patients had documentation of ineffective heart failure self-management in the domains of poor diet adherence (28.4%), missed medical encounters (26.4%) poor medication adherence (20.2%) and non-specified self-management issues (e.g., "compliance issues", 34.6%). We showed the feasibility of using text-mining to identify patients with ineffective self-management. More natural language processing algorithms are needed to help busy clinicians identify these patients.

  15. Identifying and treating common and uncommon infections in the patient with diabetes.

    PubMed

    Garrison, M W; Campbell, R K

    1993-01-01

    Patients with diabetes represent a unique group of individuals who appear more prone than others to developing infections. Several mechanisms have been proposed to explain the association between diabetes and infections. However, few conclusive studies exist and considerable debate continues regarding evidence for this predisposition. Despite this lack of documented proof, many health care practitioners acknowledge that a number of infections are overrepresented in patients with diabetes. Some of these infections appear to occur exclusively in patients with diabetes, especially patients who are poorly controlled. The presenting clinical features, causative organisms, and preferred treatment approaches will be discussed in this article for a variety of common and uncommon infections observed in patients with diabetes. In addition, the proposed predisposing factors will be addressed briefly.

  16. Identifying patient, community and program specific barriers to free specialty care utilization by uninsured patients in East Baltimore.

    PubMed

    Handy, Catherine; Ma, Sai; Block, Lauren; de la Torre, Desiree; Langley, Anne; Cook, Barbara

    2013-05-01

    Uninsured individuals face multiple barriers to accessing specialty care. The Access Partnership (TAP) offers free specialty care and care coordination to qualified uninsured patients at an urban academic medical center for a small program entry fee (waived for financial hardship). In the program's first year, 104 eligible patients (31%) did not enroll. To understand why, we investigated demographic, referral, personal, and program-specific factors. After adjusting for age, gender, and ZIP code, diagnostic and therapeutic referrals were more likely to be completed than ancillary referrals (OR=8.56, p=.001; OR 3.53, p=.03). There was no difference between pain related and ancillary referrals (OR=2.80, p=.139). Eighteen patients were surveyed and reported program and patient-specific barriers. While removing costs is necessary to improve access to specialty care for underserved patients, it is insufficient. Improving communication from program coordinators and enrollment strategies may help to improve utilization of free care programs by the uninsured.

  17. Identifying medical-surgical nursing staff perceptions of the drug-abusing patient.

    PubMed

    Nilsen, Stacy L; Stone, Wendy L; Burleson, Stephanie L

    2013-01-01

    Nurses report a negative, stereotypical, and moralistic view of substance-abusing patients. Unaddressed bias may impede delivery of quality care. There is limited research of the needs specific to medical-surgical nursing staff interacting with substance-abusing patients. Nursing therapeutic commitment refers to the degree the nurse feels prepared with an adequate knowledge base, professional support, and personal ownership of a patient condition. Low therapeutic commitment correlates with job dissatisfaction. The Drug and Drug Problems Perceptions Questionnaire assesses healthcare provider attitude and therapeutic commitment to patients using or abusing medication or illicit substances. This therapeutic commitment survey serves as a staff needs assessment for a targeted educational innovation. The results show that the medical and surgical nursing staff has a constructive attitude and a moderately high degree of therapeutic commitment to the drug-abusing patient population, similar to more specialized multidisciplinary, mental healthcare workers. This study showed that medical-surgical nurses feel professionally responsible and clinically supported with patients with primary or comorbid drug abuse. Consistent with established results, focused and ongoing education on the risk factors, outcomes, and physical and psychological effects of illicit substances is necessary to improve therapeutic commitment to drug-dependent patients.

  18. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome.

    PubMed

    Villamor, N; Conde, L; Martínez-Trillos, A; Cazorla, M; Navarro, A; Beà, S; López, C; Colomer, D; Pinyol, M; Aymerich, M; Rozman, M; Abrisqueta, P; Baumann, T; Delgado, J; Giné, E; González-Díaz, M; Hernández, J M; Colado, E; Payer, A R; Rayon, C; Navarro, B; José Terol, M; Bosch, F; Quesada, V; Puente, X S; López-Otín, C; Jares, P; Pereira, A; Campo, E; López-Guillermo, A

    2013-04-01

    NOTCH1 has been found recurrently mutated in a subset of patients with chronic lymphocytic leukemia (CLL). To analyze biological features and clinical impact of NOTCH1 mutations in CLL, we sequenced this gene in 565 patients. NOTCH1 mutations, found in 63 patients (11%), were associated with unmutated IGHV, high expression of CD38 and ZAP-70, trisomy 12, advanced stage and elevated lactate dehydrogenase. Sequential analysis in 200 patients demonstrated acquisition of mutation in one case (0.5%) and disappearance after treatment in two. Binet A and B patients with NOTCH1-mutated had a shorter time to treatment. NOTCH1-mutated patients were more frequently refractory to therapy and showed shorter progression-free and overall survival after complete remission. Overall survival was shorter in NOTCH1-mutated patients, although not independently from IGHV. NOTCH1 mutation increased the risk of transformation to diffuse large B-cell lymphoma independently from IGHV, with this being validated in resampling tests of replicability. In summary, NOTCH1 mutational status, that was rarely acquired during the course of the disease, identify a genetic subgroup with high risk of transformation and poor outcome. This recently identified genetic subgroup of CLL patients deserves prospective studies to define their best management.

  19. Single Nucleotide Variations in CLCN6 Identified in Patients with Benign Partial Epilepsies in Infancy and/or Febrile Seizures

    PubMed Central

    Yamamoto, Toshiyuki; Shimojima, Keiko; Sangu, Noriko; Komoike, Yuta; Ishii, Atsushi; Abe, Shinpei; Yamashita, Shintaro; Imai, Katsumi; Kubota, Tetsuo; Fukasawa, Tatsuya; Okanishi, Tohru; Enoki, Hideo; Tanabe, Takuya; Saito, Akira; Furukawa, Toru; Shimizu, Toshiaki; Milligan, Carol J.; Petrou, Steven; Heron, Sarah E.; Dibbens, Leanne M.; Hirose, Shinichi; Okumura, Akihisa

    2015-01-01

    Nucleotide alterations in the gene encoding proline-rich transmembrane protein 2 (PRRT2) have been identified in most patients with benign partial epilepsies in infancy (BPEI)/benign familial infantile epilepsy (BFIE). However, not all patients harbor these PRRT2 mutations, indicating the involvement of genes other than PRRT2. In this study, we performed whole exome sequencing analysis for a large family affected with PRRT2-unrelated BPEI. We identified a non-synonymous single nucleotide variation (SNV) in the voltage-sensitive chloride channel 6 gene (CLCN6). A cohort study of 48 BPEI patients without PRRT2 mutations revealed a different CLCN6 SNV in a patient, his sibling and his father who had a history of febrile seizures (FS) but not BPEI. Another study of 48 patients with FS identified an additional SNV in CLCN6. Chloride channels (CLCs) are involved in a multitude of physiologic processes and some members of the CLC family have been linked to inherited diseases. However, a phenotypic correlation has not been confirmed for CLCN6. Although we could not detect significant biological effects linked to the identified CLCN6 SNVs, further studies should investigate potential CLCN6 variants that may underlie the genetic susceptibility to convulsive disorders. PMID:25794116

  20. Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome.

    PubMed

    Martínez-Trillos, Alejandra; Pinyol, Magda; Navarro, Alba; Aymerich, Marta; Jares, Pedro; Juan, Manel; Rozman, María; Colomer, Dolors; Delgado, Julio; Giné, Eva; González-Díaz, Marcos; Hernández-Rivas, Jesús M; Colado, Enrique; Rayón, Consolación; Payer, Angel R; Terol, Maria José; Navarro, Blanca; Quesada, Victor; Puente, Xosé S; Rozman, Ciril; López-Otín, Carlos; Campo, Elías; López-Guillermo, Armando; Villamor, Neus

    2014-06-12

    Mutations in Toll-like receptor (TLR) and myeloid differentiation primary response 88 (MYD88) genes have been found in chronic lymphocytic leukemia (CLL) at low frequency. We analyzed the incidence, clinicobiological characteristics, and outcome of patients with TLR/MYD88 mutations in 587 CLL patients. Twenty-three patients (3.9%) had mutations, 19 in MYD88 (one with concurrent IRAK1 mutation), 2 TLR2 (one with concomitant TLR6 mutation), 1 IRAK1, and 1 TLR5. No mutations were found in IRAK2 and IRAK4. TLR/MYD88-mutated CLL overexpressed genes of the nuclear factor κB pathway. Patients with TLR/MYD88 mutations were significantly younger (83% age ≤50 years) than those with no mutations. TLR/MYD88 mutations were the most frequent in young patients. Patients with mutated TLR/MYD88 CLL had a higher frequency of mutated IGHV and low expression of CD38 and ZAP-70. Overall survival (OS) was better in TLR/MYD88-mutated than unmutated patients in the whole series (10-year OS, 100% vs 62%; P = .002), and in the subset of patients age ≤50 years (100% vs 70%; P = .02). In addition, relative OS of TLR/MYD88-mutated patients was similar to that in the age- and gender-matched population. In summary, TLR/MYD88 mutations identify a population of young CLL patients with favorable outcome.

  1. Accuracy of Conventional Diagnostic Methods for Identifying Structural Changes in Patients with Focal Epilepsy

    PubMed Central

    Dakaj, Nazim; Kruja, Jera; Jashari, Fisnik; Boshnjaku, Dren; Shatri, Nexhat; Zeqiraj, Kamber

    2016-01-01

    Background: Epilepsy is a neurological disorder characterized by abnormal firing of nerve impulses in the brain. Aim: This study aims to investigate the frequency of appearance of pathological changes in conventional examination methods (electroencephalography–EEG, brain computerized tomography -CT or brain magnetic resonance imaging – MRI) in patients with epilepsy, and relationship between clinical manifestations and localization of changes in CT or MRI. Methods: In this study we have included 110 patients with focal epilepsy who fulfilled the inclusion criteria out of 557 initially diagnosed patients. Detailed clinical examination together with brain imaging (CT and MRI) and electroencephalography examination was performed. We have evaluated the accuracy of each diagnostic method to localize the epileptic focus. Diagnosis of epilepsy was determined by the ILAE (International League Against Epilepsy) criteria of the year 1989, and classification of epileptic seizures was made according to the ILAE classification 2010. Results: Electroencephalography presented changes in 60.9% of patients; brain CT in 42.1%, and MRI in 78% of the patients. The results of our study showed that clinical manifestations were not always conveyed with pathological changes in conventional examining methods performed. Of the total of 79 patients with changes in imaging (8 with changes in CT and 71 in MRI), 79.7% presented a clinical picture compatible with the region in which morphological changes were found, while in 20.3% of patients the presented morphological changes were not aligned with the clinical picture. Conclusion: In patients with epilepsy, conventional examination methods do not always find pathological changes, while clinical manifestations of epilepsy did not always coincide with the location of changes in imaging. Further studies are needed to see if there is clear border between focal and generalized epilepsy. PMID:28077892

  2. Automated Analysis of Vital Signs Identified Patients with Substantial Bleeding Prior to Hospital Arrival

    DTIC Science & Technology

    2015-10-01

    culminating with the first and only deployment of an automated emergency care decision system on board active air ambulances: the APPRAISE system , a...hardware/software platform for automated, real-time analysis of vital-sign data. After developing the APPRAISE system using data from trauma patients...APPRAISE system provided consistent determination of whether or not patients were bleeding. We found that the automated APPRAISE system using a

  3. Identifying Patients Who Need a Change in Depression Treatment and Implementing That Change.

    PubMed

    Papakostas, George I

    2016-08-01

    For patients whose depression is difficult to treat or treatment-resistant, physicians must make an educated choice to switch, augment, or combine therapies to help patients adequately respond after initial treatment selections fail. Uncover some of the complexities of this challenging diagnosis by following the case of Robert, a 55-year-old accountant whose inadequate response to treatment by his primary care doctor has prompted a referral to a specialist.

  4. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    SciTech Connect

    Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E. . E-mail: m.j.e.mourits@og.umcg.nl

    2006-11-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery.

  5. Volatile Organic Metabolites Identify Patients with Mesangial Proliferative Glomerulonephritis, IgA Nephropathy and Normal Controls

    PubMed Central

    Wang, Changsong; Feng, Yue; Wang, Mingao; Pi, Xin; Tong, Hongshuang; Wang, Yue; Zhu, Lin; Li, Enyou

    2015-01-01

    Urinary volatile organic compounds (VOCs) analysis for kidney diseases has attracted a large amount of scientific interest recently, and urinary metabolite analysis has already been applied to many diseases. Urine was collected from 15 mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy (IgAN) patients and 15 healthy controls. Solid phase microextraction–chromatography– mass spectrometry (SPME-GC-MS) was used to analyse the urinary metabolites. The statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to process the final data. Five metabolites were significantly greater in the group of MsPGN patients than in the normal control group (P < 0.05) while three metabolites were found at increased levels in the group of IgAN patients compared with the normal controls (P < 0.05). In addition, five metabolites were significantly increased in the group of IgAN patients compared with the MsPGN patients (P < 0.05). These five metabolites may be specific biomarkers for distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to have potential clinical applications as a diagnostic tool. PMID:26443483

  6. Measuring cross-cultural patient safety: identifying barriers and developing performance indicators.

    PubMed

    Walker, Roger; St Pierre-Hansen, Natalie; Cromarty, Helen; Kelly, Len; Minty, Bryanne

    2010-01-01

    Medical errors and cultural errors threaten patient safety. We know that access to care, quality of care and clinical safety are all impacted by cultural issues. Numerous approaches to describing cultural barriers to patient safety have been developed, but these taxonomies do not provide a useful set of tools for defining the nature of the problem and consequently do not establish a sound base for problem solving. The Sioux Lookout Meno Ya Win Health Centre has implemented a cross-cultural patient safety (CCPS) model (Walker 2009). We developed an analytical CCPS framework within the organization, and in this article, we detail the validation process for our framework by way of a literature review and surveys of local and international healthcare professionals. We reinforce the position that while cultural competency may be defined by the service provider, cultural safety is defined by the client. In addition, we document the difficulties surrounding the measurement of cultural competence in terms of patient outcomes, which is an underdeveloped dimension of the field of patient safety. We continue to explore the correlation between organizational performance and measurable patient outcomes.

  7. Identifying differentially expressed genes in cancer patients using a non-parameter Ising model.

    PubMed

    Li, Xumeng; Feltus, Frank A; Sun, Xiaoqian; Wang, James Z; Luo, Feng

    2011-10-01

    Identification of genes and pathways involved in diseases and physiological conditions is a major task in systems biology. In this study, we developed a novel non-parameter Ising model to integrate protein-protein interaction network and microarray data for identifying differentially expressed (DE) genes. We also proposed a simulated annealing algorithm to find the optimal configuration of the Ising model. The Ising model was applied to two breast cancer microarray data sets. The results showed that more cancer-related DE sub-networks and genes were identified by the Ising model than those by the Markov random field model. Furthermore, cross-validation experiments showed that DE genes identified by Ising model can improve classification performance compared with DE genes identified by Markov random field model.

  8. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

    PubMed Central

    Cueto Ladrón de Guevara, Antonio; Puche, Jose L.; Ruiz Zafra, Javier; de Miguel-Pérez, Diego; Ramos, Abel Sánchez-Palencia; Giraldo-Ospina, Carlos Fernando; Navajas Gómez, Juan A.; Delgado-Rodriguez, Miguel; Lorente, Jose A.; Serrano, María Jose

    2016-01-01

    Background Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. Patients and Methods 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. Results 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0–84) preoperatively and 0.66 (range 0–3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50–21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091–0.961, p = 0.043) were independent prognostic factors for DFS. Conclusion CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence. PMID:26913536

  9. Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

    PubMed Central

    Michaud, Laurent; Ludwig, Gundula; Berney, Sylvie; Rodrigues, Stéphanie; Niquille, Anne; Santschi, Valérie; Favre, Anne-Sophie; Lange, Anne-Catherine; Michels, Annemieke A.; Vrijens, Bernard; Bugnon, Olivier; Pilon, Nathalie; Pascual, Manuel; Venetz, Jean-Pierre; Stiefel, Friedrich; Schneider, Marie-Paule

    2016-01-01

    Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20). Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20). Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid

  10. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations

    PubMed Central

    Boylan, Brian; Rice, Anne S.; De Staercke, Christine; Eyster, M. Elaine; Yaish, Hassan M.; Knoll, Christine M.; Bean, Christopher J.; Miller, Connie H.

    2015-01-01

    Summary Background Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. Objectives Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. Patients/Methods Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. Results Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. Conclusions These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. PMID:25780857

  11. Identifying prognostic intratumor heterogeneity using pre- and post-radiotherapy 18F-FDG PET images for pancreatic cancer patients

    PubMed Central

    Osipov, Arsen; Fraass, Benedick; Sandler, Howard; Zhang, Xiao; Nissen, Nicholas; Hendifar, Andrew; Tuli, Richard

    2017-01-01

    Background To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. Methods Twenty-six PA patients treated with RT from 2011–2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images. A total of 48 texture and clinical variables were identified and evaluated for association with overall survival (OS). The prognostic heterogeneity features were selected using lasso/elastic net regression, and further were evaluated by multivariate Cox analysis. Results Median age was 69 y (range, 46–86 y). The texture map and temporal variations between pre- and post-treatment were well characterized by histograms and statistical fitting. The lasso analysis identified seven predictors (age, node stage, post-RT SUVmax, variations of homogeneity, variance, sum mean, and cluster tendency). The multivariate Cox analysis identified five significant variables: age, node stage, variations of homogeneity, variance, and cluster tendency (with P=0.020, 0.040, 0.065, 0.078, and 0.081, respectively). The patients were stratified into two groups based on the risk score of multivariate analysis with log-rank P=0.001: a low risk group (n=11) with a longer mean OS (29.3 months) and higher texture variation (>30%), and a high risk group (n=15) with a shorter mean OS (17.7 months) and lower texture variation (<15%). Conclusions Locoregional metabolic texture response provides a feasible approach for evaluating and predicting clinical outcomes following treatment of PA with RT. The proposed method can be used to stratify patient risk and help select appropriate treatment strategies for individual patients toward implementing response

  12. Using in vivo corneal confocal microscopy to identify diabetic sensorimotor polyneuropathy risk profiles in patients with type 1 diabetes

    PubMed Central

    Lewis, Evan J H; Perkins, Bruce A; Lovblom, Lief E; Bazinet, Richard P; Wolever, Thomas M S; Bril, Vera

    2017-01-01

    Objective Diabetic sensorimotor peripheral neuropathy (DSP) is the most prevalent complication in diabetes mellitus. Identifying DSP risk is essential for intervening early in the natural history of the disease. Small nerve fibers are affected earliest in the disease progression and evidence of this damage can be identified using in vivo corneal confocal microscopy (IVCCM). Research design and methods We applied IVCCM to a cohort of 40 patients with type 1 diabetes to identify their DSP risk profile. We measured standard IVCCM parameters including corneal nerve fiber length (CNFL), and performed nerve conduction studies and quantitative sensory testing. Results 40 patients (53% female), with a mean age of 48±14, BMI 28.1±5.8, and diabetes duration of 27±18 years were enrolled between March 2014 and June 2015. Mean IVCCM CNFL was 12.0±5.2 mm/mm2 (normal ≥15 mm/mm2). Ten patients (26%) without DSP were identified as being at risk of future DSP with mean CNFL 11.0±2.1 mm/mm2. Six patients (15%) were at low risk of future DSP with mean CNFL 19.0±4.6 mm/mm2, while 23 (59%) had established DSP with mean CNFL 10.5±4.5 mm/mm2. Conclusions IVCCM can be used successfully to identify the risk profile for DSP in patients with type 1 diabetes. This methodology may prove useful to classify patients for DSP intervention clinical trials. PMID:28243447

  13. Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype.

    PubMed

    Parenti, I; Gervasini, C; Pozojevic, J; Graul-Neumann, L; Azzollini, J; Braunholz, D; Watrin, E; Wendt, K S; Cereda, A; Cittaro, D; Gillessen-Kaesbach, G; Lazarevic, D; Mariani, M; Russo, S; Werner, R; Krawitz, P; Larizza, L; Selicorni, A; Kaiser, F J

    2016-01-01

    Cornelia de Lange syndrome (CdLS) and KBG syndrome are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, and some craniofacial and limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified in at least 70% of the patients with CdLS. Consequently, additional causative genes, either unknown or responsible of partially merging entities, possibly account for the remaining 30% of the patients. In contrast, KBG has only been associated with mutations in ANKRD11. By exome sequencing we could identify heterozygous loss-of-function mutations in ANKRD11 in two patients with the clinical diagnosis of CdLS. Both patients show features reminiscent of CdLS such as characteristic facies as well as a small head circumference which is not described for KBG syndrome. Patient A, who carries the mutation in a mosaic state, is a 4-year-old girl with features reminiscent of CdLS. Patient B, a 15-year-old boy, shows a complex phenotype which resembled CdLS during infancy, but has developed to a more KBG overlapping phenotype during childhood. These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes.

  14. Expression analysis of the genes identified in GWAS of the postmortem brain tissues from patients with schizophrenia.

    PubMed

    Umeda-Yano, Satomi; Hashimoto, Ryota; Yamamori, Hidenaga; Weickert, Cynthia Shannon; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Ito, Akira; Takeda, Masatoshi

    2014-05-07

    Many gene expression studies have examined postmortem brain tissues of patients with schizophrenia. However, only a few expression studies of the genes identified in genome-wide association study (GWAS) have been published to date. We measured the expression levels of the genes identified in GWAS (ZNF804A, OPCML, RPGRIP1L, NRGN, and TCF4) of the postmortem brain tissues of patients with schizophrenia and controls from two separate sample sets (i.e., the Australian Tissue Resource Center and Stanley Medical Research Institute). We also determined whether the single-nucleotide polymorphisms (SNPs) identified in the GWAS were related to the gene expression changes in the prefrontal cortex. No difference was observed between the patients with schizophrenia and controls from the Australian Tissue Resource Center samples in the mRNA levels of ZNF804A, OPCML, RPGRIP1L, NRGN, or TCF4. The lack of mRNA change for these five transcripts was also found in the brain samples from the Stanley Medical Research Institute. In addition, no relationship between the schizophrenia-associated SNPs identified in the GWAS and the corresponding gene expression was observed in either sample set. Our results suggest that major changes in the transcript levels of the five candidate genes identified in the GWAS may not occur in adult patients with schizophrenia. The lack of linkage between the risk gene polymorphisms and the expression levels of their major transcripts suggests that the control of pan mRNA levels may not be a prominent mechanism by which the genes identified in the GWAS contribute to the pathophysiology of schizophrenia. Further studies are needed to examine how the genes identified in the GWAS contribute to the pathophysiology of schizophrenia.

  15. Security of the distributed electronic patient record: a case-based approach to identifying policy issues.

    PubMed

    Anderson, J G

    2000-11-01

    The growth of managed care and integrated delivery systems has created a new commodity, health information and the technology that it requires. Surveys by Deloitte and Touche indicate that over half of the hospitals in the US are in the process of implementing electronic patient record (EPR) systems. The National Research Council has established that industry spends as much as $15 billion on information technology (IT), an amount that is expanding by 20% per year. The importance of collecting, electronically storing, and using the information is undisputed. This information is needed by consumers to make informed choices; by physicians to provide appropriate quality clinical care: and by health plans to assess outcomes, control costs and monitor quality. The collection, storage and communication of a large variety of personal patient data, however, present a major dilemma. How can we provide the data required by the new forms of health care delivery and at the same time protect the personal privacy of patients? Recent debates concerning medical privacy legislation, software regulation, and telemedicine suggest that this dilemma will not be easily resolved. The problem is systemic and arises out of the routine use and flow of information throughout the health industry. Health care information is primarily transferred among authorized users. Not only is the information used for patient care and financial reimbursement, secondary users of the information include medical, nursing, and allied health education, research, social services, public health, regulation, litigation, and commercial purposes such as the development of new medical technology and marketing. The main threats to privacy and confidentiality arise from within the institutions that provide patient care as well as institutions that have access to patient data for secondary purposes.

  16. [Clinico-epidemiological characteristics of mentally ill patients identified in the therapy department].

    PubMed

    Liberman, Iu I; Ostroglazov, V G; Lisina, M A; Eliava, V N

    1990-01-01

    A clinico-epidemiological study was made of the incidence of mental diseases among the adult community visiting the therapeutic department of a city polyclinic. Mental patients registered at the PND (41.9 per 1000 population) underwent examinations. A large group of patients, mainly with borderline mental diseases, was additionally revealed (134.4 per 1000 population). Therefore, the total incidence of mental diseases among the adult community amounted to 176.3 per 1000 population. Both groups are compared in terms of the clinical syndromes, sex, age, and the level of social adaptation.

  17. A new point mutation in the ND1 mitochondrial gene identified in a type II diabetic patient

    SciTech Connect

    Kalinin, V.N.; Schmidt, W.; Olek, K.

    1995-08-01

    A novel mutation in a mitochondrial gene was identified in a patient with type II diabetes mellitus. G-to-A transition was localized at the nt3316 position of gene ND1 and resulted in alanine threonine replacement at position 4 of mitochondrial NAD-H-dehydrogenase. 6 refs., 2 figs.

  18. Fatal Psychrobacter sp. infection in a pediatric patient with meningitis identified by metagenomic next-generation sequencing in cerebrospinal fluid.

    PubMed

    Ortiz-Alcántara, Joanna María; Segura-Candelas, José Miguel; Garcés-Ayala, Fabiola; Gonzalez-Durán, Elizabeth; Rodríguez-Castillo, Araceli; Alcántara-Pérez, Patricia; Wong-Arámbula, Claudia; González-Villa, Maribel; León-Ávila, Gloria; García-Chéquer, Adda Jeanette; Diaz-Quiñonez, José Alberto; Méndez-Tenorio, Alfonso; Ramírez-González, José Ernesto

    2016-03-01

    The genus Psychrobacter contains environmental, psychrophilic and halotolerant gram-negative bacteria considered rare opportunistic pathogens in humans. Metagenomics was performed on the cerebrospinal fluid (CSF) of a pediatric patient with meningitis. Nucleic acids were extracted, randomly amplified, and sequenced with the 454 GS FLX Titanium next-generation sequencing (NGS) system. Sequencing reads were assembled, and potential virulence genes were predicted. Phylogenomic and phylogenetic studies were performed. Psychrobacter sp. 310 was identified, and several virulence genes characteristic of pathogenic bacteria were found. The phylogenomic study and 16S rRNA gene phylogenetic analysis showed that the closest relative of Psychrobacter sp. 310 was Psychrobacter sanguinis. To our knowledge, this is the first report of a meningitis case associated with Psychrobacter sp. identified by NGS metagenomics in CSF from a pediatric patient. The metagenomic strategy based on NGS was a powerful tool to identify a rare unknown pathogen in a clinical case.

  19. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    PubMed Central

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  20. Comparing the Workload Perceptions of Identifying Patient Condition and Priorities of Care Among Burn Providers in Three Burn ICUs.

    PubMed

    McInnis, Ian; Murray, Sarah J; Serio-Melvin, Maria; Aden, James K; Mann-Salinas, Elizabeth; Chung, Kevin K; Huzar, Todd; Wolf, Steven; Nemeth, Christopher; Pamplin, Jeremy C

    Multidisciplinary rounds (MDRs) in the burn intensive care unit serve as an efficient means for clinicians to assess patient status and establish patient care priorities. Both tasks require significant cognitive work, the magnitude of which is relevant because increased cognitive work of task completion has been associated with increased error rates. We sought to quantify this workload during MDR using the National Aeronautics and Space Administration Task Load Index (NASA-TLX). Research staff at three academic regional referral burn centers administered the NASA-TLX to clinicians during MDR. Clinicians assessed their workload associated with 1) "Identify(ing) if the patient is better, same, or worse than yesterday" and 2) "Identify(ing) the most important objectives of care for the patient today." Data were collected on clinician type, years of experience, and hours of direct patient care. Surveys were administered to 116 total clinicians, 41 physicians, 25 nurses, 13 medical students, and 37 clinicians in other roles. Clinicians with less experience reported more cognitive work when completing both tasks (P < .005). Clinicians in the "others" group (respiratory therapists, dieticians, pharmacists, etc.) reported less cognitive work than all other groups for both tasks (P < .05). The NASA-TLX was an effective tool for collecting perceptions of cognitive workload associated with MDR. Perceived cognitive work varied by clinician type and experience level when completing two key tasks. Less experience was associated with increased perceived work, potentially increasing mental error rates, and increasing risk to patients. Creating tools or work processes to reduce cognitive work may improve clinician performance.

  1. A candidate gene approach to identify modifiers of the palatal phenotype in 22q11.2 deletion syndrome patients

    PubMed Central

    Widdershoven, Josine C.C.; Bowser, Mark; Sheridan, Molly B.; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Solot, Cynthia B.; Kirschner, Richard E.; Beemer, Frits A.; Morrow, Bernice E.; Devoto, Marcella; Emanuel, Beverly S.

    2014-01-01

    Objective Palatal anomalies are one of the identifying features of 22q11.2 deletion syndrome (22q11.2DS) affecting about one third of patients. To identify genetic variants that increase the risk of cleft or palatal anomalies in 22q11.2DS patients, we performed a candidate gene association study in 101 patients with 22q11.2DS genotyped with the Affymetrix genome-wide human SNP array 6.0. Methods Patients from Children's Hospital of Philadelphia, USA and Wilhelmina Children's Hospital Utrecht, The Netherlands were stratified based on palatal phenotype (overt cleft, submucosal cleft, bifid uvula). SNPs in 21 candidate genes for cleft palate were analyzed for genotype-phenotype association. In addition, TBX1 sequencing was carried out. Quality control and association analyses were conducted using the software package PLINK. Results Genotype and phenotype data of 101 unrelated patients (63 non-cleft subjects (62.4%), 38 cleft subjects (37.6%)) were analyzed. A Total of 39 SNPs on 10 genes demonstrated a p-value ≤0.05 prior to correction. The most significant SNPs were found on FGF10. However none of the SNPs remained significant after correcting for multiple testing. Conclusions Although these results are promising, analysis of additional samples will be required to confirm that variants in these regions influence risk for cleft palate or palatal anomalies in 22q11.2DS patients. PMID:23121717

  2. Regional Colonic Transit Pattern Does Not Conclusively Identify Evacuation Disorders in Constipated Patients with Delayed Colonic Transit

    PubMed Central

    Park, Seon-Young; Burton, Duane; Busciglio, Irene; Eckert, Deborah; Camilleri, Michael

    2017-01-01

    Background/Aims After exclusion of structural diseases, chronic constipation may be associated with normal or slow transit or rectal evacuation disorders. We evaluated: (1) clinical features and anorectal function, (2) difference of regional colonic transit according to the presence or absence of evacuation disorders, and (3) association of colonic transit with gender in patients with objectively slow colonic transit. Methods We reviewed electronic medical records of 1553 patients with constipation seen by one gastroenterologist from 1994–2015 at a tertiary medical center. We identified patients with slow colonic transit using scintigraphy. Evacuation disorders were identified on clinical examination or anorectal manometry. Colonic compliance and tone were measured in 29 patients. Statistical analysis was by the Mann-Whitney rank sum test. Results Of the 207 patients (155 females, mean age 41.3 ± 15.3 [SD] years), 113 had evacuation disorders (ED+ve) and 94 did not (ED−ve). There were no significant differences in colonic transit or gastric emptying between ED+ve or ED−ve; similarly, colonic compliance, tone and responses to neostigmine were not different in ED+ve and ED−ve. Conversely, there were significant differences by gender in patients with slow colonic transit: colonic transit, small bowel transit, and gastric emptying (all P < 0.005). Conclusions Delayed colonic transit does not exclude evacuation disorders in chronic constipation. In chronic constipation and objectively slow colonic transit, females had slower gastric, small bowel, and colonic transit than males. PMID:27667753

  3. Pathologic features of metastatic lymph nodes identified from prophylactic central neck dissection in patients with papillary thyroid carcinoma.

    PubMed

    Lee, Hyoung Shin; Park, Chanwoo; Kim, Sung Won; Noh, Woong Jae; Lim, Soo Jin; Chun, Bong Kwon; Kim, Beom Su; Hong, Jong Chul; Lee, Kang Dae

    2016-10-01

    The importance of pathologic features of metastatic lymph nodes (LNs), such as size, number, and extranodal extension, has been recently emphasized in patients with papillary thyroid carcinoma (PTC). We evaluated the characteristics of metastatic LNs identified after prophylactic central neck dissection (CND) in patients with PTC. We performed a retrospective review of 1,046 patients who underwent unilateral or bilateral thyroidectomy with ipsilateral prophylactic CND. We reviewed the characteristics of the metastatic LNs and analyzed their correlation to the clinicopathologic characteristics of the primary tumor. Cervical LN metastasis after prophylactic CND was identified in 280 out of 1046 patients (26.8 %). The size of metastatic foci (≥2 mm) was independently correlated with primary tumor size (≥1 cm) (p = 0.016, OR = 1.88). Primary tumor size (≥1 cm) was also correlated to the number of metastatic LNs (≥5) (p = 0.004, OR = 3.14) and extranodal extension (p = 0.021, OR = 2.41) in univariate analysis. The size of the primary tumor affects pathologic features of subclinical LN metastasis in patients with PTC. Patients with primary tumors ≥1 cm have an increased risk of larger LN metastases (≥2 mm), an increased number of LN metastases (≥5), and a higher incidence of ENE, which should be considered in decision for prophylactic CND.

  4. Identifying high-risk post-infarction patients by autonomic testing - Below the tip of the iceberg.

    PubMed

    Bauer, Axel

    2017-03-18

    Despite major advances in medical therapies late mortality after myocardial infarction (MI) is still high. A substantial proportion of post-MI patients die from sudden cardiac death. Prophylactic implantable-cardioverter defibrillator (ICD) therapy has been established for post-MI patients with reduced left ventricular ejection fraction (LVEF ≤35%). However, most patients who die after MI have an LVEF >35%. For this large group of patients, no specific prophylactic strategies exist. There is strong evidence that measures of cardiac autonomic dysfunction after MI provide important prognostic information in post-MI patients with preserved LVEF. Combinations of autonomic markers can identify high-risk patients after MI with LVEF >35% whose prognosis is equally worse than that of patients with LVEF ≤35%. The ongoing REFINE-ICD (NCT00673842) and SMART-MI trials (NCT02594488) test different preventive strategies in high-risk post-MI patients with cardiac autonomic dysfunction and LVEF 36-50%. While REFINE-ICD follows the traditional concept of ICD-implantation, SMART-MI uses implantable cardiac monitors with remote monitoring capabilities to sensitively detect asymptomatic, but prognostically relevant arrhythmias that could trigger specific diagnostic and therapeutic interventions.

  5. Bursting the Information Bubble: Identifying Opportunities for Pediatric Patient-Centered Technology

    PubMed Central

    Miller, Andrew D; Pollack, Ari H; Pratt, Wanda

    2016-01-01

    Although hospital care is carefully documented and that information is electronically available to clinicians, few information systems exist for patients and their families to use while they are in the hospital. Information often appears trapped within the hospital room. In this paper, we present findings from three participatory design sessions that we conducted with former patients, their parents, and clinicians from a large children’s hospital. Participants discussed challenges they faced getting information while in the hospital, and then designed possible technological solutions. Participants designed technologies aimed at extending parents’ access to and involvement in patients’ care. Their designs showed opportunities for health informatics within and beyond the children’s hospital room: to allow parents and children to disseminate information from within, access information from the hospital room remotely, establish pervasive and collaborative communication with the clinical care team, and learn about their child’s care throughout the hospital stay. PMID:28269886

  6. Hypochondriasis Differs From Panic Disorder and Social Phobia: Specific Processes Identified Within Patient Groups.

    PubMed

    Höfling, Volkmar; Weck, Florian

    2017-03-01

    Studies of the comorbidity of hypochondriasis have indicated high rates of cooccurrence with other anxiety disorders. In this study, the contrast among hypochondriasis, panic disorder, and social phobia was investigated using specific processes drawing on cognitive-perceptual models of hypochondriasis. Affective, behavioral, cognitive, and perceptual processes specific to hypochondriasis were assessed with 130 diagnosed participants based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (66 with hypochondriasis, 32 with panic disorder, and 32 with social phobia). All processes specific to hypochondriasis were more intense for patients with hypochondriasis in contrast to those with panic disorder or social phobia (0.61 < d < 2.67). No differences were found between those with hypochondriasis with comorbid disorders and those without comorbid disorders. Perceptual processes were shown to best discriminate between patients with hypochondriasis and those with panic disorder.

  7. [Meglumine acridonacetate and complex therapy of patients with newly identified advanced pulmonary tuberculosis].

    PubMed

    Pravada, N S; Budritskiĭ, A M; Sukhanov, D S

    2014-01-01

    Clinical and immunological efficacy of meglumine acridonacetate (cycloferon) tablets was evaluated in complex treatment of patients with newly diagnosed advanced pulmonary tuberculosis. It was shown that the use of cycloferon according to our scheme increased the efficacy of the therapy (earlier disappearance of the disease symptoms and bacteria isolation, shorter-terms of cavern healing, more pronounced positive radiographic dynamics vs. the patients under the etiotropic therapy). The use of cycloferon normalized the number of gamma interferon receptors, increased the gamma interferon serum levels, reduced the incidence of the side effects (liver damage) due to the use of TB drugs. Such a use of cycloferon was cost effective. The use of sycloferon is possible in the complex treatment of outpatients with advanced pulmonary tuberculosis.

  8. Identifying anxiety and depressive disorders among primary care patients: a pilot study.

    PubMed

    el-Rufaie, O E; Albar, A A; Al-Dabal, B K

    1988-03-01

    One stage case-identification method, using the Arabic Version of the Hospital Anxiety and Depression Scale (HAD) was applied in a pilot study for estimating the prevalence of depressive and anxiety disorders among a group of Saudi primary care attenders. The validity of the Arabic Version of the HAD scale was previously tested and found valid with high sensitivity and specificity. The total prevalence rate of depression was 17% and that of anxiety was 16%. Seven percent of the sample suffered both depression and anxiety i.e. the total percentage of patients with depression, anxiety or both was 26%. Higher morbidity of depression was recorded among females and a higher morbidity of anxiety among male patients.

  9. Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus.

    PubMed

    Kamoi, Kyuzi; Takeda, Keiji; Hashimoto, Kaoru; Tanaka, Reiko; Okuyama, Shinya

    2013-05-01

    It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.

  10. [Clinico-psychopathological characteristics of a group of mental patients identified at the internal medicine clinic].

    PubMed

    Ostroglazov, V G; Lisina, M A

    1990-01-01

    The authors provide the clinico-psychopathological characteristics of mental patients revealed for the first time during a clinico-epidemiological study of the district therapeutic population. The predominance among them of the somatic psychopathological syndromes was established. The overwhelming majority of those conditions were found to belong to multifactorial mental diseases in whose etiology and pathogenesis the key role is played by interaction between exogenous (psychogenous) and endogenous (thymopathic) factors.

  11. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    PubMed

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  12. Persistent Maternal Cardiac Dysfunction After Preeclampsia Identifies Patients at Risk for Recurrent Preeclampsia.

    PubMed

    Valensise, Herbert; Lo Presti, Damiano; Gagliardi, Giulia; Tiralongo, Grazia Maria; Pisani, Ilaria; Novelli, Gian Paolo; Vasapollo, Barbara

    2016-04-01

    The purpose of our study was to assess cardiac function in nonpregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia. Seventy-five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case-control study and submitted to echocardiographic examination in the nonpregnant state 12 to 18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term. Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the nonpregnant state, patients with recurrent preeclampsia compared with controls and nonrecurrent preeclampsia had lower stroke volume (63 ± 14 mL versus 73 ± 12 mL and 70 ± 11 mL, P<0.05), cardiac output (4.6 ± 1.2 L versus 5.3 ± 0.9 L and 5.2 ± 1.0 L, P<0.05), higher E/E' ratio (11.02 ± 3.43 versus 7.34 ± 2.11 versus 9.03 ± 3.43, P<0.05), and higher total vascular resistance (1638 ± 261 dyne · s(-1) · cm(-5) versus 1341 ± 270 dyne · s(-1) · cm(-5) and 1383 ± 261 dyne · s(-1) · cm(-5), P<0.05). Left ventricular mass index was higher in both recurrent and nonrecurrent preeclampsia compared with controls (30.0 ± 6.3 g/m(2.7) and 30.4 ± 6.8 g/m(2.7) versus 24.8 ± 5.0 g/m(2.7), P<0.05). Signs of diastolic dysfunction and different left ventricular characteristics are present in the nonpregnant state before a second pregnancy with recurrent preeclampsia. Previous preeclamptic patients with nonrecurrent preeclampsia show left ventricular structural and functional features intermediate with respect to controls and recurrent preeclampsia.

  13. IDENTIFYING ELEVEN FACTORS OF SERVICE MARKETING MIX (4PS) EFFECTIVE ON TENDENCY OF PATIENTS TOWARD PRIVATE HOSPITAL

    PubMed Central

    Hosseini, Seyed Mojtaba; Etesaminia, Samira; Jafari, Mehrnoosh

    2016-01-01

    Introduction: One of the important factors of correct management is to identify the reasons for patient tendency toward private hospitals. This study measures these factors based on service marketing mixes. Patients and methods: This study used a cross sectional descriptive methodology. The study was conducted during 6 months in 2015. The studied population included patients of private hospitals in Tehran. Random sampling was used (n = 200). Data was collected by an author-made questionnaire for service marketing factors. Reliability and validity of the questionnaire were confirmed. Data analysis was done using factor analysis test in SPSS 20. Results: The results showed that constant attendance of physicians and nurses has the highest effect (0.707%) on patient tendency toward private hospitals. PMID:27999486

  14. Eight Mutations of Three Genes (EDA, EDAR, and WNT10A) Identified in Seven Hypohidrotic Ectodermal Dysplasia Patients

    PubMed Central

    Zeng, Binghui; Xiao, Xue; Li, Sijie; Lu, Hui; Lu, Jiaxuan; Zhu, Ling; Yu, Dongsheng; Zhao, Wei

    2016-01-01

    Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1–6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient’s total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients. PMID:27657131

  15. Identifying Patients for Clinical Studies from Electronic Health Records: TREC 2012 Medical Records Track at OHSU

    DTIC Science & Technology

    2012-11-01

    with peripheral neuropathy and edema"), which was surprising given that this does not appear to have been a particularly difficult topic for other...quite problematic. In developing the query, we specified the ICD-9 code or the term “edema,” and the codes or term for “ peripheral neuropathy ...Patients with peripheral neuropathy and edema (discharge_icd_codes_txt:782.3 OR report_text:"lower extremity edema" OR report_text:"foot|heel|ankle edema

  16. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients

    PubMed Central

    Fernández-Nogueira, Patricia; Bragado, Paloma; Almendro, Vanessa; Ametller, Elisabet; Rios, Jose; Choudhury, Sibgat

    2016-01-01

    The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n=96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n=1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0.0001) and distant metastasis-free survival (p < 0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0.0001) and metastasis-free survival (p < 0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. PMID:26673618

  17. SurvNet: a web server for identifying network-based biomarkers that most correlate with patient survival data.

    PubMed

    Li, Jun; Roebuck, Paul; Grünewald, Stefan; Liang, Han

    2012-07-01

    An important task in biomedical research is identifying biomarkers that correlate with patient clinical data, and these biomarkers then provide a critical foundation for the diagnosis and treatment of disease. Conventionally, such an analysis is based on individual genes, but the results are often noisy and difficult to interpret. Using a biological network as the searching platform, network-based biomarkers are expected to be more robust and provide deep insights into the molecular mechanisms of disease. We have developed a novel bioinformatics web server for identifying network-based biomarkers that most correlate with patient survival data, SurvNet. The web server takes three input files: one biological network file, representing a gene regulatory or protein interaction network; one molecular profiling file, containing any type of gene- or protein-centred high-throughput biological data (e.g. microarray expression data or DNA methylation data); and one patient survival data file (e.g. patients' progression-free survival data). Given user-defined parameters, SurvNet will automatically search for subnetworks that most correlate with the observed patient survival data. As the output, SurvNet will generate a list of network biomarkers and display them through a user-friendly interface. SurvNet can be accessed at http://bioinformatics.mdanderson.org/main/SurvNet.

  18. Identifying multiple myeloma patients using data from the French health insurance databases: Validation using a cancer registry.

    PubMed

    Palmaro, Aurore; Gauthier, Martin; Conte, Cécile; Grosclaude, Pascale; Despas, Fabien; Lapeyre-Mestre, Maryse

    2017-03-01

    This study aimed to assess the performance of several algorithms based on hospital diagnoses and the long-term diseases scheme to identify multiple myeloma patients.Potential multiple myeloma patients in 2010 to 2013 were identified using the presence of hospital records with at least 1 main diagnosis code for multiple myeloma (ICD-10 "C90"). Alternative algorithms also considered related and associated diagnoses, combination with long-term conditions, or at least 2 diagnoses. Incident patients were those with no previous "C90" codes in the past 24 or 12 months. The sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) were computed, using a French cancer registry for the corresponding area and period as the criterion standard.Long-term conditions data extracted concerned 11,559 patients (21,846 for hospital data). The registry contained 125 cases of multiple myeloma. Sensitivity was 70% when using only main hospital diagnoses (specificity 100%, PPV 79%), 76% when also considering related diagnoses (specificity 100%, PPV 74%), and 90% with associated diagnoses included (100% specificity, 64% PPV).In relation with their good performance, selected algorithms can be used to study the benefit and risk of drugs in treated multiple myeloma patients.

  19. Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

    PubMed Central

    Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A.; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

    2016-01-01

    Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. PMID:27782157

  20. microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response

    PubMed Central

    Vallacchi, Viviana; Camisaschi, Chiara; Dugo, Matteo; Vergani, Elisabetta; Deho, Paola; Gualeni, Ambra; Huber, Veronica; Gloghini, Annunziata; Maurichi, Andrea; Santinami, Mario; Sensi, Marialuisa; Castelli, Chiara; Rivoltini, Licia; Rodolfo, Monica

    2016-01-01

    Sentinel node biopsy (SNB) is a main staging biomarker in melanoma and is the first lymph node to drain the tumor, thus representing the immunological site where anti-tumor immune dysfunction is established and where potential prognostic immune markers can be identified. Here we analyzed microRNA (miR) profiles in archival tumor-positive SNBs derived from melanoma patients with different outcomes and performed an integrated analysis of transcriptional data to identify deregulated immune signaling networks. Twenty-six miRs were differentially expressed in melanoma-positive SNB samples between patients with disease progression and non-progressing patients, the majority being previously reported in the regulation of immune responses. A significant variation in miR expression levels was confirmed in an independent set of SNB samples. Integrated information from genome-wide transcriptional profiles and in vitro assessment in immune cells led to the identification of miRs associated with the regulation of the TNF receptor superfamily member 8 (TNFRSF8) gene encoding the CD30 receptor, a marker increased in lymphocytes of melanoma patients with progressive disease. These findings indicate that miRs are involved in the regulation of pathways leading to immune dysfunction in the sentinel node and may provide valuable markers for developing prognostic molecular signatures for the identification of stage III melanoma patients at risk of recurrence. PMID:27983661

  1. Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia[S

    PubMed Central

    Mendoza-Barberá, Elena; Julve, Josep; Nilsson, Stefan K.; Lookene, Aivar; Martín-Campos, Jesús M.; Roig, Rosa; Lechuga-Sancho, Alfonso M.; Sloan, John H.; Fuentes-Prior, Pablo; Blanco-Vaca, Francisco

    2013-01-01

    During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia. PMID:23307945

  2. Identifying possible asthma–COPD overlap syndrome in patients with a new diagnosis of COPD in primary care

    PubMed Central

    Baarnes, Camilla Boslev; Kjeldgaard, Peter; Nielsen, Mia; Miravitlles, Marc; Ulrik, Charlotte Suppli

    2017-01-01

    The asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) remains poorly characterised. Our aim was to describe an algorithm for identifying possible ACOS in adults with newly diagnosed COPD in primary care. General practitioners (n=241) consecutively recruited subjects ⩾35 years, with tobacco exposure, at least one respiratory symptom and no previous diagnosis of obstructive lung disease. Possible ACOS was defined as chronic airflow obstruction, i.e., post-bronchodilator (BD) forced expiratory volume 1/forced vital capacity (FEV1/FVC) ratio<0.70, combined with wheeze (ACOS wheeze) and/or significant BD reversibility (ACOS BD reversibility). Of 3,875 (50% females, mean age 57 years) subjects screened, 700 (18.1%) were diagnosed with COPD, i.e., symptom(s), tobacco exposure and chronic airflow obstruction. Indications for ACOS were found in 264 (38%) of the COPD patients. The prevalence of ACOS wheeze and ACOS BD reversibility was 27% (n=190) and 16% (n=113), respectively (P<0.001), and only 6% (n=39) of the COPD patients fulfilled both criteria for ACOS. Patients with any ACOS were younger (P=0.04), had more dyspnoea (P<0.001), lower FEV1%pred (67% vs. 74%; P<0.001) and lower FEV1/FVC ratio (P=0.001) compared with COPD-only patients. Comparing subjects fulfilling both criteria for ACOS with those fulfilling criteria for ACOS wheeze only (n=151) and those fulfilling criteria for ACOS BD reversibility only (n=74) revealed no significant differences. Irrespective of the applied ACOS definition, no significant difference in life-time tobacco exposure was found between ACOS- and COPD-only patients. In subjects with a new diagnosis of COPD, the prevalence of ACOS is high. When screening for COPD in general practice among patients with no previous diagnosis of obstructive lung disease, patients with possible ACOS may be identified by self-reported wheeze and/or BD reversibility. PMID:28055002

  3. A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker

    PubMed Central

    HEINZELMANN-SCHWARZ, VIOLA A.; NIXDORF, SHERI; VALADAN, MEHRNAZ; DICZBALIS, MONICA; OLIVIER, JAKE; OTTON, GEOFF; FEDIER, ANDRÉ; HACKER, NEVILLE F.; SCURRY, JAMES P.

    2014-01-01

    Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow’s depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow’s depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma. PMID:24535703

  4. p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify patients likely to relapse despite tamoxifen therapy

    PubMed Central

    Frackelton, A Raymond; Lu, Li; Davol, Pamela A; Bagdasaryan, Robert; Hafer, Laurie J; Sgroi, Dennis C

    2006-01-01

    Introduction Shc adapter proteins are secondary messenger proteins involved in various cellular pathways, including those mediating receptor tyrosine kinase signaling and apoptosis in response to stress. We have previously reported that high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its inhibitory p66 Shc isoform are strongly prognostic for identifying both early node-negative and more advanced, node-positive, primary breast cancers with high risk for recurrence. Because aberrant activation of tyrosine kinases upstream of Shc signaling proteins has been implicated in resistance to tamoxifen – the most widely prescribed drug for treatment of estrogen receptor-positive breast cancer – we hypothesized that Shc isoforms may identify patients at increased risk of relapsing despite tamoxifen treatment. Methods Immunohistochemical analyses of PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a population-based cohort (60 patients, 9 relapses) and, for validation, an independent external cohort (31 patients, 13 relapses) in which all patients received tamoxifen as a sole systemic adjuvant prior to relapse. Results By univariate and multivariate analyses, the Shc proteins were very strong and independent predictors of treatment failure in both the population-based cohort (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P = 0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7 to 86, P = 0.013). Conclusion These results suggest that the levels of PY-Shc and p66 Shc proteins in primary tumors identify patients at high risk for relapsing despite treatment with tamoxifen and therefore with further validation may be useful in guiding clinicians to select alternative adjuvant treatment strategies. PMID:17196107

  5. Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

    PubMed Central

    Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.

    2016-01-01

    Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025

  6. Distinct disease phases in muscles of facioscapulohumeral dystrophy patients identified by MR detected fat infiltration.

    PubMed

    Janssen, Barbara H; Voet, Nicoline B M; Nabuurs, Christine I; Kan, Hermien E; de Rooy, Jacky W J; Geurts, Alexander C; Padberg, George W; van Engelen, Baziel G M; Heerschap, Arend

    2014-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is an untreatable disease, characterized by asymmetric progressive weakness of skeletal muscle with fatty infiltration. Although the main genetic defect has been uncovered, the downstream mechanisms causing FSHD are not understood. The objective of this study was to determine natural disease state and progression in muscles of FSHD patients and to establish diagnostic biomarkers by quantitative MRI of fat infiltration and phosphorylated metabolites. MRI was performed at 3T with dedicated coils on legs of 41 patients (28 men/13 women, age 34-76 years), of which eleven were re-examined after four months of usual care. Muscular fat fraction was determined with multi spin-echo and T1 weighted MRI, edema by TIRM and phosphorylated metabolites by 3D (31)P MR spectroscopic imaging. Fat fractions were compared to clinical severity, muscle force, age, edema and phosphocreatine (PCr)/ATP. Longitudinal intramuscular fat fraction variation was analyzed by linear regression. Increased intramuscular fat correlated with age (p<0.05), FSHD severity score (p<0.0001), inversely with muscle strength (p<0.0001), and also occurred sub-clinically. Muscles were nearly dichotomously divided in those with high and with low fat fraction, with only 13% having an intermediate fat fraction. The intramuscular fat fraction along the muscle's length, increased from proximal to distal. This fat gradient was the steepest for intermediate fat infiltrated muscles (0.07±0.01/cm, p<0.001). Leg muscles in this intermediate phase showed a decreased PCr/ATP (p<0.05) and the fastest increase in fatty infiltration over time (0.18±0.15/year, p<0.001), which correlated with initial edema (p<0.01), if present. Thus, in the MR assessment of fat infiltration as biomarker for diseased muscles, the intramuscular fat distribution needs to be taken into account. Our results indicate that healthy individual leg muscles become diseased by entering a progressive phase

  7. Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts

    PubMed Central

    Park, Lara K; Maione, Anna G; Smith, Avi; Gerami-Naini, Behzad; Iyer, Lakshmanan K; Mooney, David J; Veves, Aristidis; Garlick, Jonathan A

    2014-01-01

    Diabetic foot ulcers (DFUs) are a serious complication of diabetes. Previous exposure to hyperglycemic conditions accelerates a decline in cellular function through metabolic memory despite normalization of glycemic control. Persistent, hyperglycemia-induced epigenetic patterns are considered a central mechanism that activates metabolic memory; however, this has not been investigated in patient-derived fibroblasts from DFUs. We generated a cohort of patient-derived lines from DFU fibroblasts (DFUF), and site- and age-matched diabetic foot fibroblasts (DFF) and non-diabetic foot fibroblasts (NFF) to investigate global and genome-wide DNA methylation patterns using liquid chromatography/mass spectrometry and the Illumina Infinium HumanMethylation450K array. DFFs and DFUFs demonstrated significantly lower global DNA methylation compared to NFFs (p = 0.03). Hierarchical clustering of differentially methylated probes (DMPs, p = 0.05) showed that DFFs and DFUFs cluster together and separately from NFFs. Twenty-five percent of the same probes were identified as DMPs when individually comparing DFF and DFUF to NFF. Functional annotation identified enrichment of DMPs associated with genes critical to wound repair, including angiogenesis (p = 0.07) and extracellular matrix assembly (p = 0.035). Identification of sustained DNA methylation patterns in patient-derived fibroblasts after prolonged passage in normoglycemic conditions demonstrates persistent metabolic memory. These findings suggest that epigenetic-related metabolic memory may also underlie differences in wound healing phenotypes and can potentially identify therapeutic targets. PMID:25437049

  8. Peripheral Blood Cell Gene Expression Diagnostic for Identifying Symptomatic Transthyretin Amyloidosis Patients: Male and Female Specific Signatures

    PubMed Central

    Kurian, Sunil M.; Novais, Marta; Whisenant, Thomas; Gelbart, Terri; Buxbaum, Joel N.; Kelly, Jeffery W.; Coelho, Teresa; Salomon, Daniel R.

    2016-01-01

    Background: Early diagnosis of familial transthyretin (TTR) amyloid diseases remains challenging because of variable disease penetrance. Currently, patients must have an amyloid positive tissue biopsy to be eligible for disease-modifying therapies. Endomyocardial biopsies are typically amyloid positive when cardiomyopathy is suspected, but this disease manifestation is generally diagnosed late. Early diagnosis is often difficult because patients exhibit apparent symptoms of polyneuropathy, but have a negative amyloid biopsy. Thus, there is a pressing need for an additional early diagnostic strategy for TTR-aggregation-associated polyneuropathy and cardiomyopathy. Methods and Findings: Global peripheral blood cell mRNA expression profiles from 263 tafamidis-treated and untreated V30M Familiar Amyloid Neuropathy patients, asymptomatic V30M carriers, and healthy, age- and sex-matched controls without TTR mutations were used to differentiate symptomatic from asymptomatic patients. We demonstrate that blood cell gene expression patterns reveal sex-independent, as well as male- and female-specific inflammatory signatures in symptomatic FAP patients, but not in asymptomatic carriers. These signatures differentiated symptomatic patients from asymptomatic V30M carriers with >80% accuracy. There was a global downregulation of the eIF2 pathway and its associated genes in all symptomatic FAP patients. We also demonstrated that the molecular scores based on these signatures significantly trended toward normalized values in an independent cohort of 46 FAP patients after only 3 months of tafamidis treatment. Conclusions: This study identifies novel molecular signatures that differentiate symptomatic FAP patients from asymptomatic V30M carriers as well as affected males and females. We envision using this approach, initially in parallel with amyloid biopsies, to identify individuals who are asymptomatic gene carriers that may convert to FAP patients. Upon further validation

  9. Effects of exposure to factor concentrates containing donations from identified AIDS patients

    SciTech Connect

    Jason, J.; Holman, R.C.; Dixon, G.; Lawrence, D.N.; Bozeman, L.H.; Chorba, T.L.; Tregillus, L.; Evatt, B.L.

    1986-10-03

    The authors recipients of eight lots of factors VII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV), T-cell subset numbers, T-helper to T-suppressor ratios, or immunogloubulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rats of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposed within this population.

  10. AIP mutation identified in a patient with acromegaly caused by pituitary somatotroph adenoma with neuronal choristoma.

    PubMed

    Nishizawa, H; Fukuoka, H; Iguchi, G; Inoshita, N; Yamada, S; Takahashi, Y

    2013-05-01

    Pituitary adenoma with neuronal choristoma (PANCH) is a rare condition that includes ganglion cells and GH-producing tumor that is characterized by sparsely granulated somatotroph cell type. However, the pathophysiology of this condition remains to be elucidated. We report a case of 46-year-old woman with acromegaly caused by PANCH. The patient had a large and invasive macroadenoma that was resistant to preoperative therapy with somatostatin analogue (SSA) and dopamine agonist. Histological examination showed typical diffuse, chromophobe-type adenoma containing ganglion cells, and sparsely granulated somatotroph cell type, which were consistent with PANCH. Genetic analysis showed heterozygous germline missense mutation in the AIP gene that results in Y261X amino acid substitution. The clinical characteristics of acromegaly associated with AIP mutations are reportedly macroadenomas with tumor extension and invasion, lower decreases in GH and IGF-I and less tumor shrinkage with SSA treatment, and sparsely granulated somatotroph cell type, which are comparable with those observed in PANCH. Taken together, the mutation in AIP gene may explain the clinical characteristics and pathogenesis of PANCH.

  11. Immunohistochemical studies on the new type of astrocytic inclusions identified in a patient with brain malformation.

    PubMed

    Kato, S; Hirano, A; Umahara, T; Herz, F; Shioda, K; Minagawa, M

    1992-01-01

    Immunohistochemical studies were carried out on the new type of cerebral cortical astrocytic inclusions recently discovered in a 20-year-old patient with maldeveloped brain and micropolygyria. The inclusions appeared as eosinophilic structures (hematoxylin and eosin stain) and did not exhibit argyrophilia (modified Bielschowsky method). The inclusions were strongly stained by the antibody against S-100 protein (S 100) and to a lesser extent by the antibody to microtubule-associated protein 1B (MAP 1B). In contrast to Rosenthal fibers, the astrocytic inclusions did not react with antibodies to alpha B-crystallin, glial fibrillary acidic protein and ubiquitin. No positive reactions were obtained with antibodies against heat-shock protein 27 (HSP 27), HSP 72, actin, vimentin, desmin, cytokeratin, myelin basic protein, beta-tubulin, MAP 2, tau protein, paired helical filament, phosphorylated neurofilament protein (NFP), nonphosphorylated NFP, synaptophysin, cathepsin D, alpha 1-antichymotrypsin, alpha 1-antitrypsin and basic fibroblast growth factor. By immunoelectron microscopy, the products of the reaction with the anti-S 100 antibody appeared as heterogeneous granular deposits and with the antibody to MAP 1B they were randomly scattered throughout the astrocytic inclusions. Our results demonstrate that the immunohistochemical profile of the recently described inclusions differs from that of Rosenthal fibers. Whether the novel inclusions are involved in congenital astrocyte dysfunction and cerebral malformation remains to be established.

  12. Identifying Patients for Overdose Prevention With ICD-9 Classification in the Emergency Department, Massachusetts, 2013-2014.

    PubMed

    Ellison, Jacqueline; Walley, Alexander Y; Feldman, James A; Bernstein, Edward; Mitchell, Patricia M; Koppelman, Elisa A; Drainoni, Mari-Lynn

    2016-09-01

    The national rise in opioid overdose deaths signifies a need to integrate overdose prevention within healthcare delivery settings. The emergency department (ED) is an opportune location for such interventions. To effectively integrate prevention services, the target population must be clearly defined. We used ICD-9 discharge codes to establish and apply overdose risk categories to ED patients seen from January 1, 2013 to December 31, 2014 at an urban safety-net hospital in Massachusetts with the goal of informing ED-based naloxone rescue kit distribution programs. Of 96,419 patients, 4,468 (4.6%) were at increased risk of opioid overdose, defined by prior opioid overdose, misuse, or polysubstance misuse. A small proportion of those at risk were prescribed opioids on a separate occasion. Use of risk categories defined by ICD-9 codes identified a notable proportion of ED patients at risk for overdose, and provides a systematic means to prioritize and direct clinical overdose prevention efforts.

  13. Association Between IHC and MSI Testing to Identify Mismatch Repair–Deficient Patients with Ovarian Cancer

    PubMed Central

    Lee, Ji-Hyun; Cragun, Deborah; Thompson, Zachary; Coppola, Domenico; Nicosia, Santo V.; Akbari, Mohammad; Zhang, Shiyu; McLaughlin, John; Narod, Steven; Schildkraut, Joellen; Sellers, Thomas A.

    2014-01-01

    Objective: In epithelial ovarian cancer, concordance between results of microsatellite instability (MSI) and immunohistochemical (IHC) testing has not been demonstrated. This study evaluated the association of MSI-high (MSI-H) status with loss of expression (LoE) of mismatch repair (MMR) proteins on IHC and assessed for potential factors affecting the strength of the association. Methods: Tumor specimens from three population-based studies of epithelial ovarian cancer were stained for MMR proteins through manual or automated methods, and results were interpreted by one of two pathologists. Tumor and germline DNA was extracted and MSI testing performed. Multivariable logistic regression models were fitted to predict loss of IHC expression based on MSI status after adjusting for staining method and reading pathologist. Results: Of 834 cases, 564 (67.6%) were concordant; 41 were classified as MSI-H with LoE and 523 as microsatellite stable (MSS) with no LoE. Of the 270 discordant cases, 83 were MSI-H with no LoE and 187 were MSS with LoE. Both IHC staining method and reading pathologist were strongly associated with discordant results. Conclusions: Lack of concordance in the current study may be related to inconsistencies in IHC testing methods and interpretation. Results support the need for validation studies before routine screening of ovarian tumors is implemented in clinical practice for the purpose of identifying Lynch syndrome. PMID:24592941

  14. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations.

    PubMed

    Hou, Tie Zheng; Verma, Nisha; Wanders, Jennifer; Kennedy, Alan; Soskic, Blagoje; Janman, Daniel; Halliday, Neil; Rowshanravan, Behzad; Worth, Austen; Qasim, Waseem; Baxendale, Helen; Stauss, Hans; Seneviratne, Suranjith; Neth, Olaf; Olbrich, Peter; Hambleton, Sophie; Arkwright, Peter D; Burns, Siobhan O; Walker, Lucy S K; Sansom, David M

    2017-03-16

    Heterozygous CTLA-4 deficiency has been reported as a monogenic cause of common variable immune deficiency with features of immune dysregulation. Direct mutation in CTLA-4 leads to defective regulatory T-cell (Treg) function associated with impaired ability to control levels of the CTLA-4 ligands, CD80 and CD86. However, additional mutations affecting the CTLA-4 pathway, such as those recently reported for LRBA, indirectly affect CTLA-4 expression, resulting in clinically similar disorders. Robust phenotyping approaches sensitive to defects in the CTLA-4 pathway are therefore required to inform understanding of such immune dysregulation syndromes. Here, we describe assays capable of distinguishing a variety of defects in the CTLA-4 pathway. Assessing total CTLA-4 expression levels was found to be optimal when restricting analysis to the CD45RA(-)Foxp3(+) fraction. CTLA-4 induction following stimulation, and the use of lysosomal-blocking compounds, distinguished CTLA-4 from LRBA mutations. Short-term T-cell stimulation improved the capacity for discriminating the Foxp3(+) Treg compartment, clearly revealing Treg expansions in these disorders. Finally, we developed a functionally orientated assay to measure ligand uptake by CTLA-4, which is sensitive to ligand-binding or -trafficking mutations, that would otherwise be difficult to detect and that is appropriate for testing novel mutations in CTLA-4 pathway genes. These approaches are likely to be of value in interpreting the functional significance of mutations in the CTLA-4 pathway identified by gene-sequencing approaches.

  15. Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome.

    PubMed

    Piao, Jinhua; Sakurai, Naoto; Iwamoto, Shotaro; Nishioka, Junji; Nakatani, Kaname; Komada, Yoshihiro; Mizutani, Shuki; Takagi, Masatoshi

    2013-10-01

    Most p53 mutations identified in Li-Fraumeni syndrome (LFS) are missense mutations; splicing mutations have rarely been reported. A novel splicing p53 mutation was identified in a patient with Li-Fraumeni-like syndrome (LFL). Usually, p53 missense mutants identified in LFS and cancer cells function as dominant negative mutations interfering with wild-type p53 function. However, the mechanism by which p53 haploinsufficiency causes carcinogenesis is not well characterized. In this study, we describe a novel splicing mutation that results in the loss-of-function of p53. These findings suggest a linkage between the loss-of-function type p53 mutation and a LFL phenotype.

  16. Relation of microchannel structure identified by optical coherence tomography to plaque vulnerability in patients with coronary artery disease.

    PubMed

    Kitabata, Hironori; Tanaka, Atsushi; Kubo, Takashi; Takarada, Shigeho; Kashiwagi, Manabu; Tsujioka, Hiroto; Ikejima, Hideyuki; Kuroi, Akio; Kataiwa, Hideaki; Ishibashi, Kohei; Komukai, Kenichi; Tanimoto, Takashi; Ino, Yasushi; Hirata, Kumiko; Nakamura, Nobuo; Mizukoshi, Masato; Imanishi, Toshio; Akasaka, Takashi

    2010-06-15

    Increased neovascularization in atherosclerotic plaques is associated with plaque vulnerability. The high resolution of optical coherence tomography (OCT) might provide a chance to directly visualize plaque neovascularization in vivo. The aim of the present study was to investigate the relation between microchannels in culprit plaques identified by OCT and plaque vulnerability in patients with coronary artery disease. A total of 63 consecutive patients with coronary artery disease who had undergone both OCT and intravascular ultrasound before any interventions to examine culprit lesion morphologies were enrolled. Microchannel was defined as a no-signal tubuloluminal structure on the cross-sectional optical coherence tomographic image. Microchannels were found in 24 (38%) of the 63 patients. The patients were divided into 2 groups according to the presence or absence of microchannels. The frequency of plaque rupture tended to be greater in the microchannel group (50% vs 28%, p = 0.11). The thickness of the fibrous cap (median 60 vs 100 microm, p = 0.001) was significantly less in the patients with microchannels, and significant differences were found in the frequency of thin-cap fibroatheroma (54% vs 21%, p = 0.012) and positive remodeling (67% vs 36%, p = 0.02) between the 2 groups. The high-sensitivity C-reactive protein levels in the microchannel group was significantly greater than those in the no-microchannel group (median 0.27 vs 0.13 mg/dl, p = 0.015). Moreover, increased microchannel counts were associated with greater high-sensitivity C-reactive protein levels (p = 0.01). In conclusion, a significant relation was found between the presence of microchannels in plaques identified by OCT and plaque vulnerability in patients with coronary artery disease.

  17. Optomap ultrawide field imaging identifies additional retinal abnormalities in patients with diabetic retinopathy

    PubMed Central

    Price, Liam D; Au, Stephanie; Chong, N Victor

    2015-01-01

    Purpose To compare diabetic retinopathy (DR) severity grading between Optomap ultrawide field scanning laser ophthalmoscope (UWFSLO) 200° images and an Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard field view. Methods Optomap UWFSLO images (total: 266) were retrospectively selected for evidence of DR from a database of eye clinic attendees. The Optomap UWFSLO images were graded for DR severity by two masked assessors. An ETDRS seven-field mask was overlaid on the Optomap UWFSLO images, and the DR grade was assessed for the region inside the mask. Any interassessor discrepancies were adjudicated by a senior retinal specialist. Kappa agreement levels were used for statistical analysis. Results Fifty images (19%) (P<0.001) were assigned a higher DR level in the Optomap UWFSLO view compared to the ETDRS seven-field view, which resulted in 40 images (15%) (P<0.001) receiving a higher DR severity grade. DR severity grades in the ETDRS seven-field view compared with the Optomap UWFSLO view were identical in 85% (226) of the images and within one severity level in 100% (266) of the images. Agreement between the two views was substantial: unweighted κ was 0.74±0.04 (95% confidence interval: 0.67–0.81) and weighted κ was 0.80±0.03 (95% confidence interval: 0.74–0.86). Conclusion Compared to the ETDRS seven-field view, a significant minority of patients are diagnosed with more severe DR when using the Optomap UWFSLO view. The clinical significance of additional peripheral lesions requires evaluation in future prospective studies using large cohorts. PMID:25848202

  18. VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma

    PubMed Central

    Ferreira, Rafael Fernandes; Pinhel, Marcela Augusta de Souza; da Silva, Renato Ferreira; Fucuta, Patrícia da Silva; Souza, Dorotéia Rossi Silva

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC. PMID:27660750

  19. Accelerated bone turnover identifies hemiplegic patients at higher risk of demineralization.

    PubMed

    Del Puente, A; Pappone, N; Servodio Iammarrone, C; Esposito, A; Scarpa, R; Costa, L; Caso, F; Bardoscia, A; Del Puente, A

    2016-01-01

    Immobilization osteoporosis represents a severe complication in hemiplegic patients (HPs), causing fragility fractures, which may occur during rehabilitation reducing functional recovery and survival. The aim of the study was to investigate determinants of bone loss, independent from length of immobilization, which may be useful in early identification of HPs at higher risk of demineralization. Forty-eight HPs of both sexes underwent anthropometric measurements, evaluation of scores of spasticity and of lower limb motory capacity. Laboratory tests were performed. On serum: calcium; phosphorus; creatinine; ALP; iPTH; 25(OH) vitamin-D; sex hormones; Δ4-androstenedione; DHEA-S; insulin; IGF-1; FT3; FT4; TSH; c-AMP. On urine: c-AMP and calcium/creatinine ratio. Two bone turnover markers were measured: serum osteocalcin (BGP) and urinary deoxypyridinoline (DPD). Bone mineral density was determined at both femoral necks, defining a percentage difference in bone loss between paretic and non-paretic limb, thus controlling for the complex cofactors involved. Only bone turnover markers significantly and directly correlated with the entity of demineralization, controlling for age, sex and length of immobilization in the multivariate analysis (BGP coefficient estimate=0.008; SE=0.003; p=0.020; DPD coefficient estimate=0.005; SE=0.002; p=0.036). BGP and DPD are not dependent on anthropometric and endocrine-metabolic parameters, disability patterns and duration of immobilization, thus represent independent determinants of the degree of demineralization. A cutoff was defined for BGP and DPD above which subjects show significantly greater risk of demineralization. The immobilization event generates more severe bone loss when it occurs in subjects with higher bone turnover. BGP and DPD measurements may be of primary importance for early identification of HPs at risk, with relevant preventive implications.

  20. Abnormal expression and dysfunction of novel SGLT2 mutations identified in familial renal glucosuria patients.

    PubMed

    Yu, Lei; Lv, Ji-Cheng; Zhou, Xu-jie; Zhu, Li; Hou, Ping; Zhang, Hong

    2011-03-01

    Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and in the absence of overt tubular dysfunction. Mutation of sodium/glucose co-transporter 2 (SGLT2) has been identified and was recently reported to be involved in FRG. However, the functional and pathological consequences of such mutations remain unknown. In the current study, we collected four families with FRG. Sequencing of the SGLT2 coding region, intronic segments and cDNA revealed three missense mutations (294C>A: F98L; 1388T>G: L463R; 1435C>G: R479G) and two splice mutations (IVS 1-16 C>A: Del exon3; IVS 11+1 G>C: Del exon11). The probands were either heterozygous or compound heterozygous for SGLT2 mutations, and had glucosuria quantified at 6-27 g/day. Human 293 cells were transfected with the plasmid constructs to study the expression and function of SGLT2 mutants in vitro. Confocal microscopy using green fluorescent protein (GFP) revealed that the mutation results in a loss of punctate membrane pattern typical of the wild-type SGLT2 except in the 294C>A mutant. All mutants had significantly lower transport capacity in comparison to the wild-type control (26.49-71.48%). Renal biopsy in one consenting proband revealed significantly lower SGLT2 expression in the apical side of the proximal convoluted tubule in comparison to both healthy and disease controls (minimal change disease and diabetic nephropathy). The current study provides functional clues regarding the SGLT2 molecule from genotype to phenotype in FRG families.

  1. 12-Chemokine Gene Signature Identifies Lymph Node-like Structures in Melanoma: Potential for Patient Selection for Immunotherapy?

    NASA Astrophysics Data System (ADS)

    Messina, Jane L.; Fenstermacher, David A.; Eschrich, Steven; Qu, Xiaotao; Berglund, Anders E.; Lloyd, Mark C.; Schell, Michael J.; Sondak, Vernon K.; Weber, Jeffrey S.; Mulé, James J.

    2012-10-01

    We have interrogated a 12-chemokine gene expression signature (GES) on genomic arrays of 14,492 distinct solid tumors and show broad distribution across different histologies. We hypothesized that this 12-chemokine GES might accurately predict a unique intratumoral immune reaction in stage IV (non-locoregional) melanoma metastases. The 12-chemokine GES predicted the presence of unique, lymph node-like structures, containing CD20+ B cell follicles with prominent areas of CD3+ T cells (both CD4+ and CD8+ subsets). CD86+, but not FoxP3+, cells were present within these unique structures as well. The direct correlation between the 12-chemokine GES score and the presence of unique, lymph nodal structures was also associated with better overall survival of the subset of melanoma patients. The use of this novel 12-chemokine GES may reveal basic information on in situ mechanisms of the anti-tumor immune response, potentially leading to improvements in the identification and selection of melanoma patients most suitable for immunotherapy.

  2. Identifying Measures Used for Assessing Quality of YouTube Videos with Patient Health Information: A Review of Current Literature

    PubMed Central

    Fernandez-Luque, Luis; Armayones, Manuel; Lau, Annie YS

    2013-01-01

    Background Recent publications on YouTube have advocated its potential for patient education. However, a reliable description of what could be considered quality information for patient education on YouTube is missing. Objective To identify topics associated with the concept of quality information for patient education on YouTube in the scientific literature. Methods A literature review was performed in MEDLINE, ISI Web of Knowledge, Scopus, and PsychINFO. Abstract selection was first conducted by two independent reviewers; discrepancies were discussed in a second abstract review with two additional independent reviewers. Full text of selected papers were analyzed looking for concepts, definitions, and topics used by its authors that focused on the quality of information on YouTube for patient education. Results In total, 456 abstracts were extracted and 13 papers meeting eligibility criteria were analyzed. Concepts identified related to quality of information for patient education are categorized as expert-driven, popularity-driven, or heuristic-driven measures. These include (in descending order): (1) quality of content in 10/13 (77%), (2) view count in 9/13 (69%), (3) health professional opinion in 8/13 (62%), (4) adequate length or duration in 6/13 (46%), (5) public ratings in 5/13 (39%), (6) adequate title, tags, and description in 5/13 (39%), (7) good description or a comprehensive narrative in 4/13 (31%), (8) evidence-based practices included in video in 4/13 (31%), (9) suitability as a teaching tool in 4/13 (31%), (10) technical quality in 4/13 (31%), (11) credentials provided in video in 4/13 (31%), (12) enough amount of content to identify its objective in 3/13 (23%), and (13) viewership share in 2/13 (15%). Conclusions Our review confirms that the current topics linked to quality of information for patient education on YouTube are unclear and not standardized. Although expert-driven, popularity-driven, or heuristic-driven measures are used as proxies to

  3. Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure

    PubMed Central

    Pagano, D; Bonser, R; Townend, J; Ordoubadi, F; Lorenzoni, R; Camici, P

    1998-01-01

    Objective—To compare the predictive value of dobutamine echocardiography (DE) and positron emission tomography (PET) in identifying reversible chronic left ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary artery disease (CAD) and overt heart failure.
Patients—30 patients (four women) with CAD and heart failure undergoing coronary artery bypass grafting (CABG).
Methods—Myocardial viability was assessed with DE (5 and 10 µg/kg/min) and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at baseline and six months after CABG.
Results—192 of the 336 (57%) dysfunctional LV segments improved function following CABG (hibernating) and the LV ejection fraction (EF) increased from 23(7) to 32(9)% (p < 0.0001) (in 17 patients > 5%). DE and PET had similar positive predictive values (68% and 66%) in the identification of hibernating myocardium, but DE had a significantly lower negative predictive value than PET (54% v 96%; p < 0.0001). A significant linear correlation was found between the number of PET viable segments and the changes in EF following CABG (r = 0.65; p = 0.0001). Stepwise logistic regression identified the number of PET viable segments as an independent predictor of improvement in EF > 5%, whereas the number of DE viable segments, the baseline LVEF, and wall motion were not.
Conclusions—DE has a higher false negative rate than PET in identifying recoverable LV dysfunction in patients with severe postischaemic heart failure. The amount of PET viable myocardium correlates with the functional outcome following CABG.

 Keywords: dobutamine echocardiography;  positron emission tomography;  coronary artery disease;  heart failure;  hibernating myocardium PMID:9602663

  4. Analysis of the discrepancies identified during medication reconciliation on patient admission in cardiology units: a descriptive study

    PubMed Central

    Lombardi, Natália Fracaro; Mendes, Antonio Eduardo Matoso; Lucchetta, Rosa Camila; Reis, Wálleri Christini Torelli; Fávero, Maria Luiza Drechsel; Correr, Cassyano Januário

    2016-01-01

    ABSTRACT Objectives: this observational study aimed to describe the discrepancies identified during medication reconciliation on patient admission to cardiology units in a large hospital. Methods: the medication history of patients was collected within 48 hours after admission, and intentional and unintentional discrepancies were classified as omission, duplication, dose, frequency, timing, and route of drug administration. Results: most of the patients evaluated were women (58.0%) with a mean age of 59 years, and 75.5% of the patients had a Charlson comorbidity index score between 1 and 3. Of the 117 discrepancies found, 50.4% were unintentional. Of these, 61.0% involved omission, 18.6% involved dosage, 18.6% involved timing, and 1.7% involved the route of drug administration. Conclusion: this study revealed a high prevalence of discrepancies, most of which were related to omissions, and 50% were unintentional. These results reveal the number of drugs that are not reincorporated into the treatment of patients, which can have important clinical consequences. PMID:27533269

  5. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  6. The Effect of Physician Continuing Medical Education on Patient-Reported Outcomes for Identifying and Optimally Managing Obstructive Sleep Apnea

    PubMed Central

    Johnson, Sara S.; Castle, Patricia H.; Van Marter, Deborah; Roc, Anne; Neubauer, David; Auerbach, Sanford; DeAguiar, Emma

    2015-01-01

    Study Objective: To evaluate the effect of continuing medical education (CME) activities on patient reported outcomes with regard to (1) screening for excessive sleepiness (ES) and obstructive sleep apnea (OSA) and (2) appropriate referral and treatment. Methods: A total of 725 patients were recruited from 75 providers who either participated or did not participate in Transtheoretical Model (TTM)-based OSA CME activities. Patient reported outcomes from participating (n = 36) and non-participating providers (n = 39) were compared using generalized estimating equations examining random effects of provider as unit of assignment. Results: Patients' reports demonstrate that participating physicians were 1.7 times more likely to initiate discussion of sleep problems than non-participating physicians (t1,411 = 3.71, p = 0.05) and 2.25–2.86 times more likely to administer validated measures for OSA (Epworth Sleepiness Scale and STOP-BANG). Patient reports also indicated that participating clinicians (79.9%) were significantly more likely to recommend seeing a sleep specialist compared to non-participating clinicians (60.7%; t1,348 = 9.1, p < 0.01, OR = 2.6). Furthermore, while 89.4% of participating clinicians recommended a sleep study, only 73.2% of the non-participating physicians recommended one (t1,363 = 11.46, p < 0.001, OR = 3.1). Conclusions: Participation in TTM-based OSA CME activities was associated with improved patient reported outcomes compared to the non-participating clinicians. Citation: Johnson SS, Castle PH, Van Marter D, Roc A, Neubauer D, Auerbach S, DeAguiar E. The effect of physician continuing medical education on patient-reported outcomes for identifying and optimally managing obstructive sleep apnea. J Clin Sleep Med 2015;11(3):197–204. PMID:25845903

  7. Comparing the Berlin and the ARES questionnaire to identify patients with obstructive sleep apnea in a dental setting

    PubMed Central

    Clark, Glenn T.

    2010-01-01

    Purpose The aim of this study was to compare the sensitivity and specificity of two questionnaires to identify patients with obstructive sleep apnea (OSA). Materials and methods Fifty-three moderate to severe OSA patients [with a respiratory disturbance index (RDI)≥15] and 31 controls (RDI<15) based on ambulatory somnographic assessment were recruited through flyers and mail at USC School of Dentistry. Each patient answered the Berlin and apnea risk evaluation system (ARES) questionnaires. The responses to the questionnaires were scored and compared for significant group differences. Results Moderate and severe OSA patients were predominantly male, older, had a larger neck size, and larger body mass index than controls. There were no significant differences in race or ethnicity between the two groups. In this study, subjects having a “high risk” ARES questionnaire were 7.9 times as likely to have OSA as subjects with “low or no risk” score (p=0.0002). The ARES questionnaire had a sensitivity of 90.6%, specificity of 43.2%, a positive predictive value (PPV) of 73.8%, and negative predictive value (NPV) of 73.7% compared to 67.9%, 54.8%, 72%, and 50%, respectively, for the Berlin questionnaire using a cut point of RDI≥15. Conclusions In this specific patient group, not uncommon to the regular dental private practice, the ARES questionnaire performed better than the Berlin questionnaire with higher sensitivity, similar PPV, higher NPV, but lower specificity. The lower specificity could be explained in part because the ARES has been tailored to screen patients with an RDI≥5, and our study included mostly mild to severe patients. In conclusion, in this specific group of subjects, the ARES questionnaire is a better choice than the Berlin questionaire; however, the Berlin questionnaire is publicly available and the ARES screener is proprietary. PMID:20127186

  8. A retrospective observational analysis to identify patient and treatment-related predictors of outcomes in a community mental health programme

    PubMed Central

    Green, Stuart A; Honeybourne, Emmi; Chalkley, Sylvia R; Price, Geraint; Bell, Derek; Green, John

    2015-01-01

    Objectives This study aims to identify patient and treatment factors that affect clinical outcomes of community psychological therapy through the development of a predictive model using historic data from 2 services in London. In addition, the study aims to assess the completeness of data collection, explore how treatment outcomes are discriminated using current criteria for classifying recovery, and assess the feasibility and need for undertaking a future larger population analysis. Design Observational, retrospective discriminant analysis. Setting 2 London community mental health services that provide psychological therapies for common mental disorders including anxiety and depression. Participants A total of 7388 patients attended the services between February 2009 and May 2012, of which 4393 (59%) completed therapy, or there was an agreement to end therapy, and were included in the study. Primary and secondary outcome measures Different combinations of the clinical outcome scores for anxiety Generalised Anxiety Disorder-7 and depression Patient Health Questionnaire-9 were used to construct different treatment outcomes. Results The predictive models were able to assign a positive or negative clinical outcome to each patient based on 5 independent pre-treatment variables, with an accuracy of 69.4% and 79.3%, respectively: initial severity of anxiety and depression, ethnicity, deprivation and gender. The number of sessions attended/missed were also important factors identified in recovery. Conclusions Predicting whether patients are likely to have a positive outcome following treatment at entry might allow suitable modification of scheduled treatment, possibly resulting in improvements in outcomes. The model also highlights factors not only associated with poorer outcomes but inextricably linked to prevalence of common mental disorders, emphasising the importance of social determinants not only in poor health but also poor recovery. PMID:25995234

  9. Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer

    PubMed Central

    Dobbin, Zachary C.; Katre, Ashwini A.; Steg, Adam D.; Erickson, Britt K.; Shah, Monjri M.; Alvarez, Ronald D.; Conner, Michael G.; Schneider, David; Chen, Dongquan; Landen, Charles N.

    2014-01-01

    A cornerstone of preclinical cancer research has been the use of clonal cell lines. However, this resource has underperformed in its ability to effectively identify novel therapeutics and evaluate the heterogeneity in a patient's tumor. The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy, but also basic tenets of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor's heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of six pair of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer PMID:25209969

  10. Identifying barriers and improving communication between cancer service providers and Aboriginal patients and their families: the perspective of service providers

    PubMed Central

    2013-01-01

    Background Aboriginal Australians experience poorer outcomes from cancer compared to the non-Aboriginal population. Some progress has been made in understanding Aboriginal Australians’ perspectives about cancer and their experiences with cancer services. However, little is known of cancer service providers’ (CSPs) thoughts and perceptions regarding Aboriginal patients and their experiences providing optimal cancer care to Aboriginal people. Communication between Aboriginal patients and non-Aboriginal health service providers has been identified as an impediment to good Aboriginal health outcomes. This paper reports on CSPs’ views about the factors impairing communication and offers practical strategies for promoting effective communication with Aboriginal patients in Western Australia (WA). Methods A qualitative study involving in-depth interviews with 62 Aboriginal and non-Aboriginal CSPs from across WA was conducted between March 2006 - September 2007 and April-October 2011. CSPs were asked to share their experiences with Aboriginal patients and families experiencing cancer. Thematic analysis was carried out. Our analysis was primarily underpinned by the socio-ecological model, but concepts of Whiteness and privilege, and cultural security also guided our analysis. Results CSPs’ lack of knowledge about the needs of Aboriginal people with cancer and Aboriginal patients’ limited understanding of the Western medical system were identified as the two major impediments to communication. For effective patient–provider communication, attention is needed to language, communication style, knowledge and use of medical terminology and cross-cultural differences in the concept of time. Aboriginal marginalization within mainstream society and Aboriginal people’s distrust of the health system were also key issues impacting on communication. Potential solutions to effective Aboriginal patient-provider communication included recruiting more Aboriginal staff

  11. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE

    PubMed Central

    Nava, C; Lamari, F; Héron, D; Mignot, C; Rastetter, A; Keren, B; Cohen, D; Faudet, A; Bouteiller, D; Gilleron, M; Jacquette, A; Whalen, S; Afenjar, A; Périsse, D; Laurent, C; Dupuits, C; Gautier, C; Gérard, M; Huguet, G; Caillet, S; Leheup, B; Leboyer, M; Gillberg, C; Delorme, R; Bourgeron, T; Brice, A; Depienne, C

    2012-01-01

    The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the ɛ-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium. PMID:23092983

  12. Exome sequencing identifies frequent mutation of MLL2 in non–small cell lung carcinoma from Chinese patients

    PubMed Central

    Yin, Shanye; Yang, Jing; Lin, Bin; Deng, Wenjun; Zhang, Yuchao; Yi, Xianfu; Shi, Yufang; Tao, Yong; Cai, Jun; Wu, Chung-I; Zhao, Guoping; Hurst, Laurence D.; Zhang, Jie; Hu, Landian; Kong, Xiangyin

    2014-01-01

    Lung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-κB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease. PMID:25112956

  13. Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.

    PubMed

    Nava, C; Lamari, F; Héron, D; Mignot, C; Rastetter, A; Keren, B; Cohen, D; Faudet, A; Bouteiller, D; Gilleron, M; Jacquette, A; Whalen, S; Afenjar, A; Périsse, D; Laurent, C; Dupuits, C; Gautier, C; Gérard, M; Huguet, G; Caillet, S; Leheup, B; Leboyer, M; Gillberg, C; Delorme, R; Bourgeron, T; Brice, A; Depienne, C

    2012-10-23

    The striking excess of affected males in autism spectrum disorders (ASD) suggests that genes located on chromosome X contribute to the etiology of these disorders. To identify new X-linked genes associated with ASD, we analyzed the entire chromosome X exome by next-generation sequencing in 12 unrelated families with two affected males. Thirty-six possibly deleterious variants in 33 candidate genes were found, including PHF8 and HUWE1, previously implicated in intellectual disability (ID). A nonsense mutation in TMLHE, which encodes the ɛ-N-trimethyllysine hydroxylase catalyzing the first step of carnitine biosynthesis, was identified in two brothers with autism and ID. By screening the TMLHE coding sequence in 501 male patients with ASD, we identified two additional missense substitutions not found in controls and not reported in databases. Functional analyses confirmed that the mutations were associated with a loss-of-function and led to an increase in trimethyllysine, the precursor of carnitine biosynthesis, in the plasma of patients. This study supports the hypothesis that rare variants on the X chromosome are involved in the etiology of ASD and contribute to the sex-ratio disequilibrium.

  14. TU-AB-303-02: A Novel Surrogate to Identify Anatomical Changes During Radiotherapy of Head and Neck Cancer Patients

    SciTech Connect

    Gros, S; Roeske, J; Surucu, M

    2015-06-15

    Purpose: To develop a novel method to monitor external anatomical changes in head and neck cancer patients in order to help guide adaptive radiotherapy decisions. Methods: The method, developed in MATLAB, reveals internal anatomical changes based on variations observed in external anatomy. Weekly kV-CBCT scans from 11 Head and neck patients were retrospectively analyzed. The pre-processing step first corrects each CBCT for artifacts and removes pixels from the immobilization mask to produce an accurate external contour of the patient’s skin. After registering the CBCTs to the initial planning CT, the external contours from each CBCT (CBCTn) are transferred to the first week — reference — CBCT{sub 1}. Contour radii, defined as the distances between an external contour and the central pixel of each CBCT slice, are calculated for each scan at angular increments of 1 degree. The changes in external anatomy are then quantified by the difference in radial distance between the external contours of CBCT1 and CBCTn. The radial difference is finally displayed on a 2D intensity map (angle vs radial distance difference) in order to highlight regions of interests with significant changes. Results: The 2D radial difference maps provided qualitative and quantitative information, such as the location and the magnitude of external contour divergences and the rate at which these deviations occur. With this method, anatomical changes due to tumor volume shrinkage and patient weight loss were clearly identified and could be correlated with the under-dosage of targets or over-dosage of OARs. Conclusion: This novel method provides an efficient tool to visualize 3D external anatomical modification on a single 2D map. It quickly pinpoints the location of differences in anatomy during the course of radiotherapy, which can help determine if a treatment plan needs to be adapted.

  15. Comparison of methods to identify aberrant expression patterns in individual patients: augmenting our toolkit for precision medicine

    PubMed Central

    2013-01-01

    Background Patient-specific aberrant expression patterns in conjunction with functional screening assays can guide elucidation of the cancer genome architecture and identification of therapeutic targets. Since most statistical methods for expression analysis are focused on differences between experimental groups, the performance of approaches for patient-specific expression analyses are currently less well characterized. A comparison of methods for the identification of genes that are dysregulated relative to a single sample in a given set of experimental samples, to our knowledge, has not been performed. Methods We systematically evaluated several methods including variations on the nearest neighbor based outlying degree method, as well as the Zscore and a robust variant for their suitability to detect patient-specific events. The methods were assessed using both simulations and expression data from a cohort of pediatric acute B lymphoblastic leukemia patients. Results We first assessed power and false discovery rates using simulations and found that even under optimal conditions, high effect sizes (>4 unit differences) were necessary to have acceptable power for any method (>0.9) though high false discovery rates (>0.1) were pervasive across simulation conditions. Next we introduced a technical factor into the simulation and found that performance was reduced for all methods and that using weights with the outlying degree could provide performance gains depending on the number of samples and genes affected by the technical factor. In our use case that highlights the integration of functional assays and aberrant expression in a patient cohort (the identification of gene dysregulation events associated with the targets from a siRNA screen), we demonstrated that both the outlying degree and the Zscore can successfully identify genes dysregulated in one patient sample. However, only the outlying degree can identify genes dysregulated across several patient samples

  16. Disturbances in hypothalamo pituitary adrenal and thyroid axis identify different sleep EEG patterns in major depressed patients.

    PubMed

    Staner, L; Duval, F; Haba, J; Mokrani, M C; Macher, J P

    2003-01-01

    This study was aimed at investigating the relationships between sleep EEG abnormalities and hypothalamo pituitary adrenal (HPA) and hypothalamo pituitary thyroid (HPT) disturbances in major depressive disorder. Post dexamethasone (DXM) cortisol levels and the dual TSH response to 08:00 h and 23:00 h TRH administration were determined after a 2 weeks wash-out period in a group of 113 DSM-IV major depressed patients (72 females aged 44.3+/-13.0 and 41 males aged 45.7+/-11) who were consecutively admitted to undergo sleep EEG recordings. Post-DXM cortisolemia, 08:00 and 23:00 post-TRH TSH values, time spent in rapid eye movement sleep (REMS), in slow wave sleep (SWS), and in stage 2 as well as time awake after sleep onset were introduced in a principal component (PC) analysis. The four 3 PC scores explaining up to 74% of the data set were further calculated for each patients and used in a cluster analysis. A three-cluster solution was retained. Controlling for the effects of age and gender, patients belonging to these three clusters could clearly be differentiated on the basis of their neuroendocrine responses and on their sleep EEG profiles. Compared to the two other clusters, cluster I (n=26) patients showed the most severe sleep continuity disturbances. Post-DXM cortisol escape and sleep architecture disturbances (consisting of a shortening of REMS latency and a decreased SWS) identified patients belonging to cluster II (n=39). Patients in cluster III (n=48) had the lowest TSH response to TRH and the less marked sleep EEG alteration. Clinical or demographic variables were unable to differentiate the three clusters. Our results suggest that different biological dysfunctions could each underlie particular neuroendocrine and sleep EEG disturbances in major depression.

  17. To Identify Predictors of Central Lymph Node Metastasis in Patients with Clinically Node-Negative Conventional Papillary Thyroid Carcinoma

    PubMed Central

    Zhao, Gang; Du, Jialin; Chen, Xiaoyi; Lin, Xiaodong; Chen, Zhengbo

    2016-01-01

    Objective. The aim of this study was to identify the risk factors associated with central lymph node metastasis (CLNM) in patients with clinically node-negative conventional papillary thyroid carcinoma (cN0 CPTC). Methods. A total of 190 cN0 CPTC patients who underwent thyroidectomy with prophylactic central neck dissection (pCND) in the Department of General Surgery at Guangdong General Hospital between March 2014 and December 2015 were assessed retrospectively. The relations of CLNM with clinicopathologic characteristics of cN0 CPTC were analyzed by univariate and multivariate logistic regression. Results. The incidence of CLNM in patients with cN0 CPTC was 63.2% (120 of 190 cases). Univariate analysis showed that age <45 years (P = 0.000), tumor size >2 cm (P = 0.009), multifocality (P = 0.001), and bilaterality (P = 0.000) were significantly associated with the increased incidence of CLNM in cN0 CPTC. No significant correlations were found between CLNM and other variables such as gender (P = 0.150), capsular invasion (P = 0.973), extrathyroidal invasion (P = 0.616), and lymphadenectomy (P = 0.062). Multivariate logistic regression analysis revealed that age <45 years (P = 0.000), tumor size >2 cm (P = 0.025), and bilaterality (P = 0.000) were independent risk factors of CLNM in patients with cN0 CPTC. Conclusions. Metastatic disease to central compartment lymph nodes is prevalent in patients with cN0 CPTC. Age <45 years, tumor size >2 cm, and bilaterality are independent risk factors of CLNM, which allow for selective CND in patients with cN0 CPTC. PMID:28074094

  18. Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia

    PubMed Central

    Ladroue, Charline; Hoogewijs, David; Gad, Sophie; Carcenac, Romain; Storti, Federica; Barrois, Michel; Gimenez-Roqueplo, Anne-Paule; Leporrier, Michel; Casadevall, Nicole; Hermine, Olivier; Kiladjian, Jean-Jacques; Baruchel, André; Fakhoury, Fadi; Bressac-de Paillerets, Brigitte; Feunteun, Jean; Mazure, Nathalie; Pouysségur, Jacques; Wenger, Roland H.; Richard, Stéphane; Gardie, Betty

    2012-01-01

    Background Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia. This mutant displays a weak deficiency in hypoxia inducible factor α regulation and does not promote tumorigenesis. Other von Hippel-Lindau mutants with more deleterious effects are responsible for von Hippel-Lindau disease, which is characterized by the development of multiple tumors. Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosis not associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma. Design and Methods Five PHD2 variants, four of which were novel, were identified in patients with erythrocytosis. These PHD2 variants were functionally analyzed and compared with the PHD2 mutant previously identified in a patient with polycythemia and paraganglioma. The capacity of PHD2 to regulate the activity, stability and hydroxylation of hypoxia inducible factor α was assessed using hypoxia-inducible reporter gene, one-hybrid and in vitro hydroxylation assays, respectively. Results This functional comparative study showed that two categories of PHD2 mutants could be distinguished: one category with a weak deficiency in hypoxia inducible factor α regulation and a second one with a deleterious effect; the mutant implicated in tumor occurrence belongs to the second category. Conclusions As observed with germline von Hippel-Lindau mutations, there are functional differences between the PHD2 mutants with regards to hypoxia inducible factor regulation. PHD2 mutation carriers do, therefore, need careful medical follow-up, since some mutations must be considered as potential candidates for

  19. Identify-Isolate-Inform: A Tool for Initial Detection and Management of Measles Patients in the Emergency Department

    PubMed Central

    Koenig, Kristi L.; Alassaf, Wajdan; Burns, Michael J.

    2015-01-01

    Measles (rubeola) is a highly contagious airborne disease that was declared eliminated in the U.S. in the year 2000. Only sporadic U.S. cases and minor outbreaks occurred until the larger outbreak beginning in 2014 that has become a public health emergency. The “Identify-Isolate-Inform” tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Measles typically presents with a prodrome of high fever, and cough/coryza/conjunctivitis, sometimes accompanied by the pathognomonic Koplik spots. Two to four days later, an erythematous maculopapular rash begins on the face and spreads down the body. Suspect patients must be immediately isolated with airborne precautions while awaiting laboratory confirmation of disease. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases. PMID:25834659

  20. Identify-isolate-inform: a tool for initial detection and management of measles patients in the emergency department.

    PubMed

    Koenig, Kristi L; Alassaf, Wajdan; Burns, Michael J

    2015-03-01

    Measles (rubeola) is a highly contagious airborne disease that was declared eliminated in the U.S. in the year 2000. Only sporadic U.S. cases and minor outbreaks occurred until the larger outbreak beginning in 2014 that has become a public health emergency. The "Identify-Isolate-Inform" tool will assist emergency physicians to be better prepared to detect and manage measles patients presenting to the emergency department. Measles typically presents with a prodrome of high fever, and cough/coryza/conjunctivitis, sometimes accompanied by the pathognomonic Koplik spots. Two to four days later, an erythematous maculopapular rash begins on the face and spreads down the body. Suspect patients must be immediately isolated with airborne precautions while awaiting laboratory confirmation of disease. Emergency physicians must rapidly inform the local public health department and hospital infection control personnel of suspected measles cases.

  1. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria.

    PubMed

    Shen, Hongzhang; Ye, Fuqiang; Xie, Lu; Yang, Jianfeng; Li, Zhen; Xu, Peisong; Meng, Fei; Li, Lei; Chen, Ying; Bo, Xiaochen; Ni, Ming; Zhang, Xiaofeng

    2015-12-02

    Despite the high worldwide prevalence of gallstone disease, the role of the biliary microbiota in gallstone pathogenesis remains obscure. Next-generation sequencing offers advantages for systematically understanding the human microbiota; however, there have been few such investigations of the biliary microbiome. Here, we performed whole-metagenome shotgun (WMS) sequencing and 16S rRNA sequencing on bile samples from 15 Chinese patients with gallstone disease. Microbial communities of most individuals were clustered into two types, according to the relative enrichment of different intestinal bacterial species. In the bile samples, oral cavity/respiratory tract inhabitants were more prevalent than intestinal inhabitants and existed in both community types. Unexpectedly, the two types were not associated with fever status or surgical history, and many bacteria were patient-specific. We identified 13 novel biliary bacteria based on WMS sequencing, as well as genes encoding putative proteins related to gallstone formation and bile resistance (e.g., β-glucuronidase and multidrug efflux pumps). Bile samples from gallstone patients had reduced microbial diversity compared to healthy faecal samples. Patient samples were enriched in pathways related to oxidative stress and flagellar assembly, whereas carbohydrate metabolic pathways showed varying behaviours. As the first biliary WMS survey, our study reveals the complexity and specificity of biliary microecology.

  2. Identifying clinical and support-service resources and network practices for cancer patients and survivors in southern Puerto Rico

    PubMed Central

    Castro, Eida M.; Jiménez, Julio C.; Quinn, Gwendolyn; García, Myra; Colón, Yesenia; Ramos, Axel; Brandon, Thomas; Simmons, Vani; Gwede, Clement; Vadaparampil, Susan; Nazario, Cruz María

    2015-01-01

    Objective The objectives of this study were to identify cancer-related health care services and to explore the presence of inter-organizational interactions among clinical and support oncology services in southern Puerto Rico. Methods From January through July of 2010, a survey was completed by 54 health care organizations offering clinical, supportive, or both services to cancer patients/survivors (CPS) in southern PR. Survey data were compiled and descriptive analyses performed using the software Statistical Package for a Social Science (SPSS), version 18.0. Results The distribution of the primary services provided by the participating organizations was the following: 26 had clinical services, 16 had support services, and 12 offered a combination of clinical and support services. Only 24% of the surveyed organizations offered their services exclusively to patients diagnosed with cancer. In terms of referral practices, 61% of the responses were for medical specialists, 43% were for mental health services, and 37% were referrals for primary care services. The most common reason for interacting (n = 27) was to provide a given patient both an referral and information. Conclusion Findings suggest gaps in both the availability of oncology services and the delivery of integrated health care. Lack of communication among clinical and support organizations (for cancer patients, specifically) could negatively impact the quality of the services that they offer. Further network analysis studies are needed to confirm these gaps. Until systemic, structural changes occur, more efforts are needed to facilitate communication and collaboration among these kinds of organization. PMID:25249352

  3. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

    PubMed Central

    Ren, Lili; Yang, Donghong; Ren, Xianwen; Li, Mingkun; Mu, Xinlin; Wang, Qi; Cao, Jie; Hu, Ke; Yan, Chunliang; Fan, Hongwei; Li, Xiangxin; Chen, Yusheng; Wang, Ruiqin; An, Fucheng; An, Shuchang; Luo, Ming; Wang, Ying; Xiao, Yan; Xiang, Zichun; Xiao, Yan; Li, Li; Huang, Fang; Jin, Qi; Gao, Zhancheng; Wang, Jianwei

    2017-01-01

    Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs. PMID:28128353

  4. NDM-1-Producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii Identified from a Single Patient in China.

    PubMed

    Huang, Ying-Min; Zhong, Lan-Lan; Zhang, Xue-Fei; Hu, Hang-Tong; Li, Yu-Qi; Yang, Xiao-Rong; Feng, Lian-Qiang; Huang, Xi; Tian, Guo-Bao

    2015-08-01

    We identified New Delhi metallo-β-lactamase (NDM-1)-producing Citrobacter freundii GB032, Escherichia coli GB102, and Acinetobacter baumannii GB661 in urine and stool samples from a single patient in China. Plasmid profiling and Southern blotting indicated that blaNDM-1 from GB032 and that from GB102 were likely located on the same plasmid, while blaNDM-1 from GB661 was located on a very large (>400-kb) plasmid. This case underscores the broad host range of blaNDM-1 and its potential to spread between members of the family Enterobacteriaceae and A. baumannii.

  5. NDM-1-Producing Citrobacter freundii, Escherichia coli, and Acinetobacter baumannii Identified from a Single Patient in China

    PubMed Central

    Huang, Ying-Min; Zhong, Lan-lan; Zhang, Xue-Fei; Hu, Hang-tong; Li, Yu-qi; Yang, Xiao-rong; Feng, Lian-Qiang; Huang, Xi

    2015-01-01

    We identified New Delhi metallo-β-lactamase (NDM-1)-producing Citrobacter freundii GB032, Escherichia coli GB102, and Acinetobacter baumannii GB661 in urine and stool samples from a single patient in China. Plasmid profiling and Southern blotting indicated that blaNDM-1 from GB032 and that from GB102 were likely located on the same plasmid, while blaNDM-1 from GB661 was located on a very large (>400-kb) plasmid. This case underscores the broad host range of blaNDM-1 and its potential to spread between members of the family Enterobacteriaceae and A. baumannii. PMID:26055374

  6. Protein Biomarkers Identify Patients Unlikely to Benefit from Primary Prevention ICDs: Findings from the PROSE-ICD Study

    PubMed Central

    Cheng, Alan; Zhang, Yiyi; Blasco-Colmenares, Elena; Dalal, Darshan; Butcher, Barbara; Norgard, Sanaz; Eldadah, Zayd; Ellenbogen, Kenneth A.; Dickfeld, Timm; Spragg, David D.; Marine, Joseph E.; Guallar, Eliseo; Tomaselli, Gordon F.

    2015-01-01

    Background Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. Methods and Results The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1,189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary endpoint was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary endpoint was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable adjusted models, higher interleukin-6 (IL-6) levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, IL-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide, and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD. Conclusions An increase in serum biomarkers of inflammation, neurohumoral activation and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs. PMID:25273351

  7. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

    PubMed Central

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

    2016-01-01

    Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods. PMID:27460420

  8. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

    PubMed

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

    2016-12-01

    Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

  9. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease

    PubMed Central

    Butler, Timothy M.; Johnson-Camacho, Katherine; Peto, Myron; Wang, Nicholas J.; Macey, Tara A.; Korkola, James E.; Koppie, Theresa M.; Corless, Christopher L.; Gray, Joe W.; Spellman, Paul T.

    2015-01-01

    The identification of the molecular drivers of cancer by sequencing is the backbone of precision medicine and the basis of personalized therapy; however, biopsies of primary tumors provide only a snapshot of the evolution of the disease and may miss potential therapeutic targets, especially in the metastatic setting. A liquid biopsy, in the form of cell-free DNA (cfDNA) sequencing, has the potential to capture the inter- and intra-tumoral heterogeneity present in metastatic disease, and, through serial blood draws, track the evolution of the tumor genome. In order to determine the clinical utility of cfDNA sequencing we performed whole-exome sequencing on cfDNA and tumor DNA from two patients with metastatic disease; only minor modifications to our sequencing and analysis pipelines were required for sequencing and mutation calling of cfDNA. The first patient had metastatic sarcoma and 47 of 48 mutations present in the primary tumor were also found in the cell-free DNA. The second patient had metastatic breast cancer and sequencing identified an ESR1 mutation in the cfDNA and metastatic site, but not in the primary tumor. This likely explains tumor progression on Anastrozole. Significant heterogeneity between the primary and metastatic tumors, with cfDNA reflecting the metastases, suggested separation from the primary lesion early in tumor evolution. This is best illustrated by an activating PIK3CA mutation (H1047R) which was clonal in the primary tumor, but completely absent from either the metastasis or cfDNA. Here we show that cfDNA sequencing supplies clinically actionable information with minimal risks compared to metastatic biopsies. This study demonstrates the utility of whole-exome sequencing of cell-free DNA from patients with metastatic disease. cfDNA sequencing identified an ESR1 mutation, potentially explaining a patient’s resistance to aromatase inhibition, and gave insight into how metastatic lesions differ from the primary tumor. PMID:26317216

  10. Expression Profiling of Liposarcoma Yields a Multigene Predictor of Patient Outcome and Identifies Genes that Contribute to Liposarcomagenesis

    PubMed Central

    Gobble, Ryan M.; Qin, Li-Xuan; Brill, Elliott R.; Angeles, Christina V.; Ugras, Stacy; O’Connor, Rachael B.; Moraco, Nicole H.; DeCarolis, Penelope L.; Antonescu, Christina; Singer, Samuel

    2011-01-01

    Liposarcomas are the second most common type of soft tissue sarcoma but its genetics are poorly defined. To identify genes that contribute to liposarcomagenesis and serve as prognostic candidates, we undertook expression profiling of 140 primary liposarcoma samples, which were randomly split into training set (n=95) and test set (n=45). A multi-gene predictor for DRFS was developed using the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% vs. 45% for high risk score patients (P=0.001). The hazard ratio for high vs. low score, adjusted for histologic subtype, was 4.42 (95% confidence interval 1.26–15.55; P=0.021). The concordance probability for risk score was 0.732. In contrast, the concordance probability for histologic subtype, which had been considered the best predictor of outcome in liposarcoma, was 0.669. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multi-gene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. RNAi-mediated knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Taken together, our findings identify genes that appear to be involved liposarcomagenesis and have promise as therapeutic targets, and support the use of this multi-gene predictor to improve risk stratification for individual patients with liposarcoma. PMID:21335544

  11. Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia

    PubMed Central

    Kroh, Evan M.; Dowell, Alexander E.; Chéry, Lisly; Siddiqui, Javed; Nelson, Peter S.; Vessella, Robert L.; Knudsen, Beatrice S.; Chinnaiyan, Arul M.; Pienta, Kenneth J.; Morrissey, Colm; Tewari, Muneesh

    2013-01-01

    MicroRNAs (miRNAs) are small (∼22 nucleotide) non-coding RNAs that regulate a myriad of biological processes and are frequently dysregulated in cancer. Cancer-associated microRNAs have been detected in serum and plasma and hold promise as minimally invasive cancer biomarkers, potentially for assessing disease characteristics in patients with metastatic disease that is difficult to biopsy. Here we used miRNA profiling to identify cancer-associated miRNAs that are differentially expressed in sera from patients with metastatic castration resistant prostate cancer (mCRPC) as compared to healthy controls. Of 365 miRNAs profiled, we identified five serum miRNAs (miR-141, miR-200a, miR-200c, miR-210 and miR-375) that were elevated in cases compared to controls across two independent cohorts. One of these, miR-210, is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. Exposure of cultured prostate cancer cells to hypoxia led to induction of miR-210 and its release into the extracellular environment. Moreover, we found that serum miR-210 levels varied widely amongst mCRPC patients undergoing therapy, and correlated with treatment response as assessed by change in PSA. Our results suggest that (i) cancer-associated hypoxia is a frequent, previously under-appreciated characteristic of mCRPC, and (ii) serum miR-210 may be further developed as a predictive biomarker in patients with this distinct disease biology. PMID:23935962

  12. Neither too much, nor too little. The dilemma of identifying personality disorders in adolescents patients with self-reports.

    PubMed

    Magallón-Neri, Ernesto; De la Fuente, José Eugenio; Canalda, Gloria; Forns, Maria; García, Raquel; González, Esther; Lara, Anais; Castro-Fornieles, Josefina

    2014-03-30

    The study aimed to compare methods of identification of Personality Disorders (PD) in adolescent patients with psychiatric disorders. A sample of 120 Spanish adolescents with clinical disorders was assessed using the International Personality Disorder Examination (IPDE) interview, its Screening Questionnaires (IPDE-SQ) comprising the ICD-10 and DSM-IV modules, and also the Temperament Character Inventory (TCI) to identify risk of PD. The IPDE-SQ identified a risk of PD around 92-97% of the sample; 61.7% when adjusting the stricter cut-off points. The TCI showed a PD risk of 20%, whereas the prevalence of PD identified by the IPDE clinical interview was around 36-38%. The differences between the IPDE, IPDE-SQ and TCI were significant, and a low agreement among instruments was obtained. Large discrepancy between self-report instruments in identifying PD with regard to the clinical interview raises several questions concerning the use of these instruments in clinical settings on adolescents with psychiatric disorders.

  13. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  14. Accurate monotone cubic interpolation

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1991-01-01

    Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.

  15. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay.

    PubMed

    Deodhar, Atul; Mittal, Manish; Reilly, Patrick; Bao, Yanjun; Manthena, Shivaji; Anderson, Jaclyn; Joshi, Avani

    2016-07-01

    This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18-64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000-December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR] = 0.986; p < 0.0001), male (HR = 1.15; p = 0.0163), diagnosed with uveitis (HR = 1.49; p = 0.0050), referred by primary care physicians (HR = 1.96; p < 0.0001), prescribed non-steroidal anti-inflammatory drugs (HR = 1.55; p < 0.0001), disease-modifying antirheumatic drugs (HR = 1.33; p < 0.0001), and tumor necrosis factor inhibitors (HR = 1.40; p = 0.0036), and to have had spinal/pelvic X-ray prior to referral (HR = 1.28; p = 0.0003). During 2000-2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate

  16. The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients.

    PubMed

    Boursier, J; Ducancelle, A; Vergniol, J; Veillon, P; Moal, V; Dufour, C; Bronowicki, J-P; Larrey, D; Hézode, C; Zoulim, F; Fontaine, H; Canva, V; Poynard, T; Allam, S; De Lédinghen, V

    2015-12-01

    Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.

  17. A Study to Determine the Best Method to Assure the Prompt and Accurate Completion of Inpatient Medical Records of Patients Discharged from Walter Reed Army Medical Center

    DTIC Science & Technology

    1987-07-13

    patient that is initially placed on a general medicine ward but is later transferred° to the Cardiac Care Unit or to the Thoracic Surgery Ward. In the...used most frequently. After the patient is admitted to the ward, as a result of an improving or worsening condition or a requirement for surgery or...originally admitted. This action is called an inter-ward transfer. See Appendix 0 for data on inter-ward transfers. An example of this might be a cardiac

  18. Identifying a clinical signature of suicidality among patients with mood disorders: a pilot study using a machine learning approach

    PubMed Central

    Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B.; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C.

    2016-01-01

    Objective A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. Method A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to ‘train’ a machine learning algorithm. The resulting algorithm was utilized in identifying novel or ‘unseen’ individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. Results All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65%-72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Conclusion Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. PMID:26773901

  19. SU-E-T-452: Identifying Inefficiencies in Radiation Oncology Workflow and Prioritizing Solutions for Process Improvement and Patient Safety

    SciTech Connect

    Bennion, N; Driewer, J; Denniston, K; Zhen, W; Enke, C; Jacobs, K; Poole, M; McMahon, R; Wilson, K; Yager, A

    2015-06-15

    Purpose: Successful radiation therapy requires multi-step processes susceptible to unnecessary delays that can negatively impact clinic workflow, patient satisfaction, and safety. This project applied process improvement tools to assess workflow bottlenecks and identify solutions to barriers for effective implementation. Methods: We utilized the DMAIC (define, measure, analyze, improve, control) methodology, limiting our scope to the treatment planning process. From May through December of 2014, times and dates of each step from simulation to treatment were recorded for 507 cases. A value-stream map created from this dataset directed our selection of outcome measures (Y metrics). Critical goals (X metrics) that would accomplish the Y metrics were identified. Barriers to actions were binned into control-impact matrices, in order to stratify them into four groups: in/out of control and high/low impact. Solutions to each barrier were then categorized into benefit-effort matries to identify those of high benefit and low effort. Results: For 507 cases, the mean time from simulation to treatment was 235 total hours. The mean process and wait time were 60 and 132 hours, respectively. The Y metric was to increase the ratio of all non-emergent plans completed the business day prior to treatment from 47% to 75%. Project X metrics included increasing the number of IMRT QAs completed at least 24 hours prior to treatment from 19% to 80% and the number of non-IMRT plans approved at least 24 hours prior to treatment from 33% to 80%. Intervals from simulation to target contour and from initial plan completion to plan approval were identified as periods that could benefit from intervention. Barriers to actions were binned into control-impact matrices and solutions by benefit-effort matrices. Conclusion: The DMAIC method can be successfully applied in radiation therapy clinics to identify inefficiencies and prioritize solutions for the highest impact.

  20. Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer.

    PubMed

    Zhu, Tao; Gao, Yuan-Feng; Chen, Yi-Xin; Wang, Zhi-Bin; Yin, Ji-Ye; Mao, Xiao-Yuan; Li, Xi; Zhang, Wei; Zhou, Hong-Hao; Liu, Zhao-Qian

    2017-02-03

    Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.

  1. Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department.

    PubMed

    Koenig, Kristi L; Almadhyan, Abdulmajeed; Burns, Michael J

    2016-05-01

    First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2-7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod

  2. Identify-Isolate-Inform: A Tool for Initial Detection and Management of Zika Virus Patients in the Emergency Department

    PubMed Central

    Koenig, Kristi L.; Almadhyan, Abdulmajeed; Burns, Michael J.

    2016-01-01

    First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the appearance of the virus in Brazil in 2015. Approximately 80% of infected patients are asymptomatic. An association with microcephaly and other birth defects as well as Guillain-Barre Syndrome has led to a World Health Organization declaration of Zika virus as a Public Health Emergency of International Concern in February 2016. Zika virus is a vector-borne disease transmitted primarily by the Aedes aegypti mosquito. Male to female sexual transmission has been reported and there is potential for transmission via blood transfusions. After an incubation period of 2–7 days, symptomatic patients develop rapid onset fever, maculopapular rash, arthralgia, and conjunctivitis, often associated with headache and myalgias. Emergency department (ED) personnel must be prepared to address concerns from patients presenting with symptoms consistent with acute Zika virus infection, especially those who are pregnant or planning travel to Zika-endemic regions, as well as those women planning to become pregnant and their partners. The identify-isolate-inform (3I) tool, originally conceived for initial detection and management of Ebola virus disease patients in the ED, and later adjusted for measles and Middle East Respiratory Syndrome, can be adapted for real-time use for any emerging infectious disease. This paper reports a modification of the 3I tool for initial detection and management of patients under investigation for Zika virus. Following an assessment of epidemiologic risk, including travel to countries with mosquitoes that transmit Zika virus, patients are further investigated if clinically indicated. If after a rapid evaluation, Zika or other arthropod

  3. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    PubMed

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.

  4. Urinary bladder paragangliomas: How Immunohistochemistry can assist to identify patients with SDHB germ line and somatic mutations

    PubMed Central

    Giubellino, Alessio; Lara, Karlena; Martucci, Victoria; Huynh, T; Agarwal, Piyush; Pacak, Karel; Merino, Maria J

    2015-01-01

    Urinary bladder paraganglioma (paraganglioma) is a rare tumor of chromaffin cells of the sympathetic system of the urinary bladder wall. We studied 14 cases of this entity and investigated the usefulness of SDHB protein staining by immunohistochemistry (IHC) as a diagnostic tool to identify patients with bladder paragangliomas that could be associated with SDHB gene mutations, since these patient have a more aggressive disease. Eleven tumors from these patients were stained by IHC. Six out of 11 tumors were negative for SDHB staining by IHC with no cytoplasmic staining in tumor cells when compared with normal tissues. Five out of these 6 negative cases were confirmed to be positive for germline SDHB mutations. One case showed negative staining and no germline SDHB mutation, however, further investigation of the tumor revealed a somatic SDHB gene deletion. The remaining 5 cases showed strong cytoplasmic staining but they were negative for the presence of SDHB mutation. They were found to be either sporadic tumors or part of von Hippel-Lindau syndrome. Staining for SDH-A was positive in all cases. Our study confirms that there is very good correlation between the presence of an SDHB mutation, whether germline or sporadic, and negative SDHB IHC staining in urinary bladder paragangliomas, and represents the first study to demonstrate that somatic mutations can be recognized by IHC staining. PMID:26457353

  5. Identifying patients with poststroke mild cognitive impairment by pattern recognition of working memory load-related ERP.

    PubMed

    Li, Xiaoou; Yan, Yuning; Wei, Wenshi

    2013-01-01

    The early detection of subjects with probable cognitive deficits is crucial for effective appliance of treatment strategies. This paper explored a methodology used to discriminate between evoked related potential signals of stroke patients and their matched control subjects in a visual working memory paradigm. The proposed algorithm, which combined independent component analysis and orthogonal empirical mode decomposition, was applied to extract independent sources. Four types of target stimulus features including P300 peak latency, P300 peak amplitude, root mean square, and theta frequency band power were chosen. Evolutionary multiple kernel support vector machine (EMK-SVM) based on genetic programming was investigated to classify stroke patients and healthy controls. Based on 5-fold cross-validation runs, EMK-SVM provided better classification performance compared with other state-of-the-art algorithms. Comparing stroke patients with healthy controls using the proposed algorithm, we achieved the maximum classification accuracies of 91.76% and 82.23% for 0-back and 1-back tasks, respectively. Overall, the experimental results showed that the proposed method was effective. The approach in this study may eventually lead to a reliable tool for identifying suitable brain impairment candidates and assessing cognitive function.

  6. Identifying and Managing a Malpositioned Endotracheal Tube Bite Block in an Orotracheally Intubated Patient: A Case Report.

    PubMed

    Chou, Hui-Ling; Ruan, Sheng-Yuan; Wu, Huey-Dong

    2016-03-01

    The universal bite block is increasingly used in orotracheally intubated patients. Here, we report a case of pilot tube dysfunction caused by a malpositioned universal bite block in an orotracheally intubated patient. We summarize the key points on identifying and managing a malpositioned universal bite block from this case and literature review.A 74-year-old woman was emergently intubated during an episode of hyperkalemia-related cardiac arrest. A universal bite block was used for fixing the endotracheal tube. After her condition stabilized, ventilator weaning was attempted; however, a positive cuff-leak test result was observed.The cuff-leak test revealed a lack of elasticity of the pilot balloon, which was completely deflated after 2 mL of air was removed. Pilot tube dysfunction was highly suspected. The bite block was slightly pulled out, and 8 mL of air was aspirated from the pilot tube. The patient was successfully extubated without stridor and respiratory distress.Our case highlighted that a malpositioned bite block may obstruct the pilot tube, causing unfavorable consequences. While fixing the bite block on an endotracheal tube, it is crucial to ensure that the takeoff point of the pilot tube is located within the C-notch of the bite block.

  7. Differentially-expressed genes identified by suppression subtractive hybridization in the bone marrow hematopoietic stem cells of patients with psoriasis.

    PubMed

    Zhang, Zhenying; Yu, Zhen; Tian, Pan; Hou, Suchun; Han, Shixin; Tan, Xuejing; Piao, Yongjun; Liu, Xiaoming

    2014-07-01

    Psoriasis is a T cell-mediated, chronic, relapsing and inflammatory cutaneous disorder. The dysfunctional activity of T cells in patients with psoriasis is attributed to bone marrow hematopoietic stem cells (BMHSCs). To understand the pathogenic roles of BMHSCs in psoriasis, a differential gene expression analysis was performed using suppression subtractive hybridization of the BMHSCs from a patient with psoriasis and a healthy control. Using a cDNA array dot blot screening to screen 600 genes from forward- and reverse-subtracted cDNA libraries, 17 differentially-expressed sequence tags (ESTs) were identified. The genes within the ESTs were observed to be the homologs of genes that are involved in various cellular processes, including hormone signaling, RNA catabolism, protein ADP DNA base melting, transcriptional regulation, cell cycle regulation and metabolism. CD45, which was overexpressed in the psoriatic BMHSCs, was further analyzed using relative quantitative polymerase chain reaction. In addition, the levels of CD45 in the peripheral blood cells (PBCs) of the patients with psoriasis were markedly increased and closely associated with disease severity. An abnormality of hematopoietic progenitor cells, e.g., CD45 overexpression, may be transferred to PBCs via hematopoiesis, and may account for the psoriasis-inducing properties of activated T cells.

  8. Identifying patients in target customer segments using a two-stage clustering-classification approach: a hospital-based assessment.

    PubMed

    Chen, You-Shyang; Cheng, Ching-Hsue; Lai, Chien-Jung; Hsu, Cheng-Yi; Syu, Han-Jhou

    2012-02-01

    Identifying patients in a Target Customer Segment (TCS) is important to determine the demand for, and to appropriately allocate resources for, health care services. The purpose of this study is to propose a two-stage clustering-classification model through (1) initially integrating the RFM attribute and K-means algorithm for clustering the TCS patients and (2) then integrating the global discretization method and the rough set theory for classifying hospitalized departments and optimizing health care services. To assess the performance of the proposed model, a dataset was used from a representative hospital (termed Hospital-A) that was extracted from a database from an empirical study in Taiwan comprised of 183,947 samples that were characterized by 44 attributes during 2008. The proposed model was compared with three techniques, Decision Tree, Naive Bayes, and Multilayer Perceptron, and the empirical results showed significant promise of its accuracy. The generated knowledge-based rules provide useful information to maximize resource utilization and support the development of a strategy for decision-making in hospitals. From the findings, 75 patients in the TCS, three hospital departments, and specific diagnostic items were discovered in the data for Hospital-A. A potential determinant for gender differences was found, and the age attribute was not significant to the hospital departments.

  9. BRAF(V600E) Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts.

    PubMed

    Kemper, Kristel; Krijgsman, Oscar; Kong, Xiangjun; Cornelissen-Steijger, Paulien; Shahrabi, Aida; Weeber, Fleur; van der Velden, Daphne L; Bleijerveld, Onno B; Kuilman, Thomas; Kluin, Roel J C; Sun, Chong; Voest, Emile E; Ju, Young Seok; Schumacher, Ton N M; Altelaar, A F Maarten; McDermott, Ultan; Adams, David J; Blank, Christian U; Haanen, John B; Peeper, Daniel S

    2016-06-28

    The therapeutic landscape of melanoma is improving rapidly. Targeted inhibitors show promising results, but drug resistance often limits durable clinical responses. There is a need for in vivo systems that allow for mechanistic drug resistance studies and (combinatorial) treatment optimization. Therefore, we established a large collection of patient-derived xenografts (PDXs), derived from BRAF(V600E), NRAS(Q61), or BRAF(WT)/NRAS(WT) melanoma metastases prior to treatment with BRAF inhibitor and after resistance had occurred. Taking advantage of PDXs as a limitless source, we screened tumor lysates for resistance mechanisms. We identified a BRAF(V600E) protein harboring a kinase domain duplication (BRAF(V600E/DK)) in ∼10% of the cases, both in PDXs and in an independent patient cohort. While BRAF(V600E/DK) depletion restored sensitivity to BRAF inhibition, a pan-RAF dimerization inhibitor effectively eliminated BRAF(V600E/DK)-expressing cells. These results illustrate the utility of this PDX platform and warrant clinical validation of BRAF dimerization inhibitors for this group of melanoma patients.

  10. Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS.

    PubMed

    Miyagawa, Maiko; Nishio, Shin-ya; Ikeda, Takuo; Fukushima, Kunihiro; Usami, Shin-ichi

    2013-01-01

    Genetic factors, the most common etiology in severe to profound hearing loss, are one of the key determinants of Cochlear Implantation (CI) and Electric Acoustic Stimulation (EAS) outcomes. Satisfactory auditory performance after receiving a CI/EAS in patients with certain deafness gene mutations indicates that genetic testing would be helpful in predicting CI/EAS outcomes and deciding treatment choices. However, because of the extreme genetic heterogeneity of deafness, clinical application of genetic information still entails difficulties. Target exon sequencing using massively parallel DNA sequencing is a new powerful strategy to discover rare causative genes in Mendelian disorders such as deafness. We used massive sequencing of the exons of 58 target candidate genes to analyze 8 (4 early-onset, 4 late-onset) Japanese CI/EAS patients, who did not have mutations in commonly found genes including GJB2, SLC26A4, or mitochondrial 1555A>G or 3243A>G mutations. We successfully identified four rare causative mutations in the MYO15A, TECTA, TMPRSS3, and ACTG1 genes in four patients who showed relatively good auditory performance with CI including EAS, suggesting that genetic testing may be able to predict the performance after implantation.

  11. Accurate IMRT fluence verification for prostate cancer patients using ‘in-vivo’ measured EPID images and in-room acquired kilovoltage cone-beam CT scans

    PubMed Central

    2013-01-01

    Background To investigate for prostate cancer patients the comparison of ‘in-vivo’ measured portal dose images (PDIs) with predictions based on a kilovoltage cone-beam CT scan (CBCT), acquired during the same treatment fraction, as an alternative for pre-treatment verification. For evaluation purposes, predictions were also performed using the patients’ planning CTs (pCT). Methods To get reliable CBCT electron densities for PDI predictions, Hounsfield units from the pCT were mapped onto the CBCT, while accounting for non-rigidity in patient anatomy in an approximate way. PDI prediction accuracy was first validated for an anatomical phantom, using IMRT treatment plans of ten prostate cancer patients. Clinical performance was studied using data acquired for 50 prostate cancer patients. For each patient, 4–5 CBCTs were available, resulting in a total of 1413 evaluated images. Measured and predicted PDIs were compared using γ-analyses with 3% global dose difference and 3 mm distance to agreement as reference criteria. Moreover, the pass rate for automated PDI comparison was assessed. To quantify improvements in IMRT fluence verification accuracy results from multiple fractions were combined by generating a γ-image with values halfway the minimum and median γ values, pixel by pixel. Results For patients, CBCT-based PDI predictions showed a high agreement with measurements, with an average percentage of rejected pixels of 1.41% only. In spite of possible intra-fraction motion and anatomy changes, this was only slightly larger than for phantom measurements (0.86%). For pCT-based predictions, the agreement deteriorated (average percentage of rejected pixels 2.98%), due to an enhanced impact of anatomy variations. For predictions based on CBCT, combination of the first 2 fractions yielded gamma results in close agreement with pre-treatment analyses (average percentage of rejected pixels 0.63% versus 0.35%, percentage of rejected beams 0.6% versus 0%). For the p

  12. Physiologic Mechanisms Underlying the Failure of the Shock Index as a Tool for Accurate Assessment of Patient Status during Progressive Simulated Hemorrhage

    DTIC Science & Technology

    2013-08-01

    Shock index (SI), the ratio of heart rate (HR) to systolic arterial pressure (SAP), is a metric often used to diagnose patients at risk of impending...traditionally dependent on the availability of ‘‘legacy’’diagnostic markers such as heart rate (HR) and systolic arterial pressure (SAP). Since stand...use of autonomic stim- ulants such as prescription (e.g., antihistamines, decongestants) or nonprescription drugs (e.g., caffeine ) for 24 hours

  13. Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines

    PubMed Central

    Yang, Jin; Li, Yao; Chan, Lawrence; Tsai, Yi-Ting; Wu, Wen-Hsuan; Nguyen, Huy V.; Hsu, Chun-Wei; Li, Xiaorong; Brown, Lewis M.; Egli, Dieter; Sparrow, Janet R.; Tsang, Stephen H.

    2014-01-01

    While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G–Wt–G; G–Wt–G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis. PMID:24497574

  14. Parathyroid hormone variability parameters for identifying high turnover osteodystrophy disease in hemodialysis patients: an observational retrospective cohort study.

    PubMed

    De Paola, Luciano; Coppolino, Giuseppe; Bolignano, Davide; Buemi, Michele; Lombardi, Luigi

    2010-12-01

    Abnormalities in bone morphology that develop secondary to chronic kidney disease are defined as renal osteodystrophy and are identified by bone biopsy. As systematic and sequential bone biopsy is not practicable on a large number of patients, various chemical bone markers are commonly used to detect the bone remodeling status in chronic kidney disease and to grade bone disease in the clinical setting. Recent literature has considered the effect of absolute levels of parathyroid hormone (PTH) on clinical outcomes and not the measurement of their change over time, the PTH variability. In a retrospective observational study, we examined PTH variability parameters in a group of hemodialysis patients as independent risk factors for high vs. low turnover osteopathy, and investigated their usefulness with respect to commonly used markers of renal osteodystrophy. The study was conducted on 90 chronic hemodialysis patients undergoing regular treatment at the same dialysis centre (Catanzaro, Italy) with standard bicarbonate dialysis. Patients were classified into either high or medium-low turnover osteopathy for the diagnosis based on renal osteodystrophy using the following criteria: PTH ≥ 400 pg/mL associated with bone ALP ≥ 20 ng/mL. We used a regression-based measurement of PTH variability, which was characterized by different parameters: PTH-Res-SD, PTH-Slope, PTH-Intercept, PTH-Abs-Var, and PTH-Res-SD. In our analysis, these parameters of PTH variability were demonstrated to be good independent predictive factors for high turnover osteodystrophy, and they had a greater sensitivity than the use of a single and/or mean PTH measurements in renal osteodystrophy classification.

  15. hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit clear cellular electrophysiological abnormalities

    PubMed Central

    Veerman, Christiaan C.; Mengarelli, Isabella; Guan, Kaomei; Stauske, Michael; Barc, Julien; Tan, Hanno L.; Wilde, Arthur A. M.; Verkerk, Arie O.; Bezzina, Connie R.

    2016-01-01

    Brugada syndrome (BrS) is a rare cardiac rhythm disorder associated with sudden cardiac death. Mutations in the sodium channel gene SCN5A are found in ~20% of cases while mutations in other genes collectively account for <5%. In the remaining patients the genetic defect and the underlying pathogenic mechanism remain obscure. To provide insight into the mechanism of BrS in individuals without identified mutations, we here studied electrophysiological properties of cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) from 3 BrS patients who tested negative for mutations in the known BrS-associated genes. Patch clamp studies revealed no differences in sodium current (INa) in hiPSC-CMs from the 3 BrS patients compared to 2 unrelated controls. Moreover, action potential upstroke velocity (Vmax), reflecting INa, was not different between hiPSC-CMs from the BrS patients and the controls. hiPSC-CMs harboring the BrS-associated SCN5A-1795insD mutation exhibited a reduction in both INa and Vmax, demonstrating our ability to detect reduced sodium channel function. hiPSC-CMs from one of the BrS lines demonstrated a mildly reduced action potential duration, however, the transient outward potassium current (Ito) and the L-type calcium current (ICa,L), both implicated in BrS, were not different compared to the controls. Our findings indicate that ion channel dysfunction, in particular in the cardiac sodium channel, may not be a prerequisite for BrS. PMID:27485484

  16. Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines.

    PubMed

    Yang, Jin; Li, Yao; Chan, Lawrence; Tsai, Yi-Ting; Wu, Wen-Hsuan; Nguyen, Huy V; Hsu, Chun-Wei; Li, Xiaorong; Brown, Lewis M; Egli, Dieter; Sparrow, Janet R; Tsang, Stephen H

    2014-07-01

    While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.

  17. Long term follow up of prosthetic valve endocarditis: what characteristics identify patients who were treated successfully with antibiotics alone?

    PubMed Central

    Truninger, K; Jost, C; Seifert, B; Vogt, P; Follath, F; Schaffner, A; Jenni, R

    1999-01-01

    OBJECTIVE—To identify predictors for the safe use of antibiotic treatment without reoperation in patients with prosthetic valve endocarditis.
SETTING—Retrospective study in a tertiary care centre.
SUBJECTS AND DESIGN—All 49 episodes of definite prosthetic valve endocarditis (Duke criteria) diagnosed at one institution between 1980 to 1997 were analysed. Ten episodes (20%) were treated with antibiotics only (antibiotic group) and 39 episodes (80%) with combined antibiotic and surgical treatment (surgery group). The analysis included detailed study of hospital records and data on long term follow up which were obtained in all patients by a questionnaire or telephone contact with physician or patient. The length of follow up (mean (SD)) was 41 (32) months in the antibiotic group and 45 (24) months in the surgery group (NS). Long term survival was estimated by the Kaplan-Meier method and compared by the log-rank test.
RESULTS—There was no significant difference in age, history of previous endocarditis, number of previous heart operations, vegetations, emboli, type of prosthesis, or percentage of early prosthetic valve endocarditis and positive blood cultures between the two groups. In the antibiotic group, there were more enterococcal (50%; p = 0.005) and in the surgery group more staphylococcal infections (55%; p = 0.048). Annular abscesses (p < 0.0001) and aortoventricular dehiscence (p = 0.02) were more common in the surgery group. No patient in the antibiotic group had heart failure. Long term follow up showed no significant difference between the surgery and antibiotic groups regarding late mortality (14% v 18%) and five year rates of recurrent endocarditis (14% v 16%), event related mortality (14% v 3%, log-rank test), and the need for reoperation (14% v 19%; log-rank test). The only patient with conservatively treated staphylococcal prosthetic valve endocarditis died after reoperation for recurrence

  18. CE: Original Research: Identifying Hospitalized Patients at Risk for Harm: A Comparison of Nurse Perceptions vs. Electronic Risk Assessment Tool Scores.

    PubMed

    Stafos, Andrea; Stark, Susan; Barbay, Kathryn; Frost, Kristen; Jackel, David; Peters, Lindsey; Riggs, Elizabeth; Schedler, Susan; Stroud, Shalan

    2017-04-01

    : Objective: In many hospitals, nurse-led "safety huddles" are used to relay patient safety information, although whether this effectively identifies patients at risk for harm has not been determined. New electronic risk assessment tools are designed to identify patients at risk for harm during hospitalization, based on specific markers in the electronic health record. This study sought to compare the results of both methods. The findings may help to enhance decision making at the level of care delivery.

  19. Development of the regional EPR and PACS sharing system on the infrastructure of cloud computing technology controlled by patient identifier cross reference manager.

    PubMed

    Kondoh, Hiroshi; Teramoto, Kei; Kawai, Tatsurou; Mochida, Maki; Nishimura, Motohiro

    2013-01-01

    A Newly developed Oshidori-Net2, providing medical professionals with remote access to electronic patient record systems (EPR) and PACSs of four hospitals, of different venders, using cloud computing technology and patient identifier cross reference manager. The operation was started from April 2012. The patients moved to other hospital were applied. Objective is to show the merit and demerit of the new system.

  20. An Aneurysmal Left Circumflex Artery-to-Right Atrium Fistula in a Patient with Ischemic Symptoms: Accurate Diagnosis with Dual-Source CT Angiography

    SciTech Connect

    Oncel, Dilek Oncel, Guray

    2008-07-15

    In this report, we present a 55-year-old female patient with a left circumflex artery-to-right atrial fistula associated with a huge saccular aneurysm. She had undergone conventional angiography due to ischemic symptoms. In conventional angiography, a very dilated and tortuous vessel originating from the circumflex artery and continuous with a huge saccular aneurysm was visualized but the drainage site could not be demonstrated. With dual-source CT coronary angiography, the exact anatomy of this fistula was demonstrated and surgery was planned.

  1. Prognosis of locally advanced rectal cancer can be predicted more accurately using pre- and post-chemoradiotherapy neutrophil-lymphocyte ratios in patients who received preoperative chemoradiotherapy

    PubMed Central

    Sung, SooYoon; Park, Eun Young; Kay, Chul Seung

    2017-01-01

    Purpose The neutrophil-lymphocyte ratio (NLR) has been suggested as an inflammation-related factor, but also as an indicator of systemic anti-tumor immunity. We aimed to evaluate the prognostic value of the NLR and to propose a proper cut-off value in patients with locally advanced rectal cancer who received preoperative chemoradiation (CRT) followed by curative total mesorectal excision (TME). Methods A total of 110 rectal cancer patients with clinical T3-4 or node-positive disease were retrospectively analyzed. The NLR value before preoperative CRT (pre-CRT NLR) and the NLR value between preoperative CRT and surgery (post-CRT NLR) were obtained. Using a maximally selected log-rank test, cut-off values were determined as 1.75 for the pre-CRT NLR and 5.14 for the post-CRT NLR. Results Patients were grouped as follows: group A, pre-CRT NLR ≤ 1.75 and post-CRT NLR ≤ 5.14 (n = 29); group B, pre-CRT NLR > 1.75 and post-CRT NLR ≤ 5.14, or pre-CRT NLR ≤ 1.75 and post-CRT NLR > 5.14 (n = 61); group C, pre-CRT NLR > 1.75 and post-CRT NLR > 5.14 (n = 20). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) and overall survival (OS) rates showed significant differences between the NLR groups (3-year DFS rate: 92.7% vs. 73.0% vs. 47.3%, for group A, B, and C, respectively, p = 0.018; 3-year OS rate: 96.0% vs. 85.5% vs. 59.8%, p = 0.034). Multivariate analysis revealed that the NLR was an independent prognostic factor for DFS (p = 0.028). Conclusion Both the pre-CRT NLR and the post-CRT NLR have a predictive value for the prognosis of patients with locally advanced rectal cancer treated with preoperative CRT followed by curative TME and adjuvant chemotherapy. A persistently elevated post-CRT NLR may be an indicator of an increased risk of distant metastasis. PMID:28291841

  2. Functional analysis of recently identified mutations in eukaryotic translation initiation factor 2Bɛ (eIF2Bɛ) identified in Chinese patients with vanishing white matter disease.

    PubMed

    Leng, Xuerong; Wu, Ye; Wang, Xuemin; Pan, Yanxia; Wang, Jingmin; Li, Jiao; Du, Li; Dai, Lifang; Wu, Xiru; Proud, Christopher G; Jiang, Yuwu

    2011-04-01

    Vanishing white matter disease (VWM) is the first human hereditary disease known to be caused by defects in initiation of protein synthesis. Gene defects in each of the five subunits of eukaryotic translation initiation factor 2B (eIF2B α-ɛ) are responsible for the disease, although the mechanism of the pathogenesis is not well understood. In our previous study, four novel eIF2Bɛ mutations were found in Chinese patients: p.Asp62Val, p.Cys335Ser, p.Asn376Asp and p.Ser610-Asp613del. Functional analysis was performed on these mutations and the recently reported p.Arg269X. Our data showed that all resulted in a decrease in the guanine nucleotide exchange (GEF) activity of the eIF2B complex. p.Arg269X and p.Ser610-Asp613del mutants displayed the lowest activity, followed by p.Cys335Ser, p.Asn376Asp and p.Asp62Val. p.Arg269X and p.Ser610-Asp613del could not produce stable eIF2Bɛ, leading to almost complete loss-of-function. No evidence was obtained for the three missense mutations in changes in eIF2Bɛ protein level or eIF2BɛSer(540) phosphorylation, and disruption of holocomplex assembly, or binding to eIF2. All patients in our study had the classical phenotype. p.Asp62Val and p.Asn376Asp mutations caused only mildly decreased GEF activity, were probably responsible for relatively mild phenotype in cases of classical VWM.

  3. Genetic screening test for psoriatic arthritis and UVB irradiation potential responders: A new tool to identify psoriasis subpopulation patients?

    PubMed Central

    Lotti, Torello; Tognetti, Linda; Galeone, Massimiliano; Bruscino, Nicola; Moretti, Silvia; Giorgini, Simonetta

    2011-01-01

    Psoriatic arthritis (PsA) is a psoriasis-associated inflammatory disease of the joints and enthuses. The occurrence of PsA is linked to the complex interplay of gene environment, and immune system. Genetic factors have long been recognized to play an important role in PsA. Genes within the major histocompatibility complex (MHC) region have been shown to be associated with PsA. These include genes coded in the HLA region, (especially Class I antigens) and non-HLA genes (i.e., MHC class I chain-related antigen A, MICA, and TNF-α genes). Association studies in PsA have also identified a number of genes outside MHC region, including interleukin-1 (IL-1) gene cluster, killer-cell immunoglobulin-like receptors (KIRs), and IL-23R genes. Established systemic treatments for moderate-severe psoriasis and PsA may be potentially dangerous and usually time consuming for the patient and often expensive for the National Health Systems. Tests which could predict which subset of psoriatic patients could develop the most severe forms of the disease (i.e., PsA) or will respond to well-established (UVB irradiation) or other systemic treatments are now required. The goal of genetic test screening is to rapidly and safely identify subjects for preventive or early treatment or extended surveillance prior to the onset of signs and symptoms. Genetic tests today represent a reliable investigation procedure which could rapidly and consistently improve the diagnostic ability of the dermatologist and contribute to the early and correct treatment of the different subsets of PsA. PMID:23130225

  4. A pilot study for development of a novel tool for clinical decision making to identify fallers among ophthalmic patients

    PubMed Central

    2015-01-01

    Background Falls in the elderly is a major problem. Although falls have a multifactorial etiology, a commonly cited cause of falls in older people is poor vision. This study proposes a method to discriminate fallers and non-fallers among ophthalmic patients, based on data-mining algorithms applied to health and socio-demographic information. Methods A group of 150 subjects aged 55 years and older, recruited at the Eye Clinic of the Second University of Naples, underwent a baseline ophthalmic examination and a standardized questionnaire, including lifestyles, general health, social engagement and eyesight problems. A subject who reported at least one fall within one year was considered as faller, otherwise as non-faller. Different tree-based data-mining algorithms (i.e., C4.5, Adaboost and Random Forest) were used to develop automatic classifiers and their performances were evaluated by assessing the receiver-operator characteristics curve estimated with the 10-fold-crossvalidation approach. Results The best predictive model, based on Random Forest, enabled to identify fallers with a sensitivity and specificity rate of 72.6% and 77.9%, respectively. The most informative variables were: intraocular pressure, best corrected visual acuity and the answers to the total difficulty score of the Activities of Daily Vision Scale (a questionnaire for the measurement of visual disability). Conclusions The current study confirmed that some ophthalmic features (i.e. cataract surgery, lower intraocular pressure values) could be associated with a lower fall risk among visually impaired subjects. Finally, automatic analysis of a combination of visual function parameters (either self-evaluated either by ophthalmological tests) and other health information, by data-mining algorithms, could be a feasible tool for identifying fallers among ophthalmic patients. PMID:26391731

  5. Accurate quantum chemical calculations

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1989-01-01

    An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.

  6. Inflammatory and fibrotic proteins proteomically identified as key protein constituents in urine and stone matrix of patients with kidney calculi.

    PubMed

    Boonla, Chanchai; Tosukhowong, Piyaratana; Spittau, Björn; Schlosser, Andreas; Pimratana, Chaowat; Krieglstein, Kerstin

    2014-02-15

    To uncover whether urinary proteins are incorporated into stones, the proteomic profiles of kidney stones and urine collected from the same patients have to be explored. We employed 1D-PAGE and nanoHPLC-ESI-MS/MS to analyze the proteomes of kidney stone matrix (n=16), nephrolithiatic urine (n=14) and healthy urine (n=3). We identified 62, 66 and 22 proteins in stone matrix, nephrolithiatic urine and healthy urine, respectively. Inflammation- and fibrosis-associated proteins were frequently detected in the stone matrix and nephrolithiatic urine. Eighteen proteins were exclusively found in the stone matrix and nephrolithiatic urine, considered as candidate biomarkers for kidney stone formation. S100A8 and fibronectin, representatives of inflammation and fibrosis, respectively, were up-regulated in nephrolithiasis renal tissues. S100A8 was strongly expressed in infiltrated leukocytes. Fibronectin was over-expressed in renal tubular cells. S100A8 and fibronectin were immunologically confirmed to exist in nephrolithiatic urine and stone matrix, but in healthy urine they were undetectable. Conclusion, both kidney stones and urine obtained from the same patients greatly contained inflammatory and fibrotic proteins. S100A8 and fibronectin were up-regulated in stone-baring kidneys and nephrolithiatic urine. Therefore, inflammation and fibrosis are suggested to be involved in the formation of kidney calculi.

  7. Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson's disease.

    PubMed

    Sandor, Cynthia; Robertson, Paul; Lang, Charmaine; Heger, Andreas; Booth, Heather; Vowles, Jane; Witty, Lorna; Bowden, Rory; Hu, Michele; Cowley, Sally A; Wade-Martins, Richard; Webber, Caleb

    2017-01-17

    While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes. The PD LRRK2-G2019S associated profile was positively matched with expression changes induced by the Parkinsonian neurotoxin rotenone and opposed by those induced by clioquinol, a compound with demonstrated therapeutic efficacy in multiple PD models. No functional convergence amongst DE genes was observed following a similar comparison using non-purified iPSC-derived DaN-containing populations, with cellular heterogeneity appearing a greater confound than genotypic background.

  8. Identifying opportunities for sexually transmitted infection prevention: analysis of critical points in the care pathways of patients with gonorrhoea.

    PubMed

    Abu-Rajab, K; Scoular, A; Church, S; Connell, J; Winter, A; Hart, G

    2009-03-01

    We applied the principles of Hazard Analysis and Critical Control Points (HACCP) to systematically analyse the care pathway of patients diagnosed with gonorrhoea to identify potential intervention opportunities for preventive action. Data were collected on individuals with culture-positive gonococcal infection during 27 February 2003 to 08 January 2004. Qualitative data were gathered within individual semi-structured interviews. Two hundred and twenty-three gonorrhoea patient episodes were evaluated. The median interval between presentation and treatment was significantly longer in females and men having sex with men (MSM), compared with heterosexual men (P = 0.002). Females were significantly more likely to be in regular relationships at the timepoint of perceived infection acquisition than heterosexuals or MSM (P < 0.0001). Four major themes emerged from the interviews: life-stage and infection risk, determinants of risk perception around sexual encounters, attitudes to preventing re-infection and condom use. These informed three potential 'critical control points': health-related attitudes/behaviours preceding infection; access to appropriate care and optimizing health promotion to prevent further infection.

  9. DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

    SciTech Connect

    Ruebe, Claudia E.

    2010-10-01

    Purpose: To evaluate, in a pilot study, the phosphorylated H2AX ({gamma}H2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting {gamma}H2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

  10. Transcriptional Profiling of Plasmodium falciparum Parasites from Patients with Severe Malaria Identifies Distinct Low vs. High Parasitemic Clusters

    PubMed Central

    Krupka, Malkie; Williams, Chris; Seydel, Karl; Taylor, Terrie E.; Van de Peer, Yves; Regev, Aviv; Wirth, Dyann

    2012-01-01

    Background In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking. Methods and Findings We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system. Conclusions The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome. PMID:22815802

  11. Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Perfusion in Patients With Moyamoya Disease

    PubMed Central

    Zaharchuk, Greg; Do, Huy M.; Marks, Michael P.; Rosenberg, Jarrett; Moseley, Michael E.; Steinberg, Gary K.

    2011-01-01

    Background and Purpose Determining the presence and adequacy of collateral blood flow is important in cerebrovascular disease. Therefore, we explored whether a noninvasive imaging modality, arterial spin labeling (ASL) MRI, could be used to detect the presence and intensity of collateral flow using digital subtraction angiography (DSA) and stable xenon CT cerebral blood flow as gold standards for collaterals and cerebral blood flow, respectively. Methods ASL and DSA were obtained within 4 days of each other in 18 patients with Moyamoya disease. Two neurointerventionalists scored DSA images using a collateral grading scale in regions of interest corresponding to ASPECTS methodology. Two neuroradiologists similarly scored ASL images based on the presence of arterial transit artifact. Agreement of ASL and DSA consensus scores was determined, including kappa statistics. In 15 patients, additional quantitative xenon CT cerebral blood flow measurements were performed and compared with collateral grades. Results The agreement between ASL and DSA consensus readings was moderate to strong, with a weighted kappa value of 0.58 (95% confidence interval, 0.52–0.64), but there was better agreement between readers for ASL compared with DSA. Sensitivity and specificity for identifying collaterals with ASL were 0.83 (95% confidence interval, 0.77–0.88) and 0.82 (95% confidence interval, 0.76–0.87), respectively. Xenon CT cerebral blood flow increased with increasing DSA and ASL collateral grade (P<0.05). Conclusions ASL can noninvasively predict the presence and intensity of collateral flow in patients with Moyamoya disease using DSA as a gold standard. Further study of other cerebrovascular diseases, including acute ischemic stroke, is warranted. PMID:21799169

  12. Identifying high-cost patients using data mining techniques and a small set of non-trivial attributes.

    PubMed

    Izad Shenas, Seyed Abdolmotalleb; Raahemi, Bijan; Hossein Tekieh, Mohammad; Kuziemsky, Craig

    2014-10-01

    In this paper, we use data mining techniques, namely neural networks and decision trees, to build predictive models to identify very high-cost patients in the top 5 percentile among the general population. A large empirical dataset from the Medical Expenditure Panel Survey with 98,175 records was used in our study. After pre-processing, partitioning and balancing the data, the refined dataset of 31,704 records was modeled by Decision Trees (including C5.0 and CHAID), and Neural Networks. The performances of the models are analyzed using various measures including accuracy, G-mean, and Area under ROC curve. We concluded that the CHAID classifier returns the best G-mean and AUC measures for top performing predictive models ranging from 76% to 85%, and 0.812 to 0.942 units, respectively. We also identify a small set of 5 non-trivial attributes among a primary set of 66 attributes to identify the top 5% of the high cost population. The attributes are the individual׳s overall health perception, age, history of blood cholesterol check, history of physical/sensory/mental limitations, and history of colonic prevention measures. The small set of attributes are what we call non-trivial and does not include visits to care providers, doctors or hospitals, which are highly correlated with expenditures and does not offer new insight to the data. The results of this study can be used by healthcare data analysts, policy makers, insurer, and healthcare planners to improve the delivery of health services.

  13. Impact of geometric mean imaging in the accurate determination of partial function in MAG3 renal scanning in a patient with retroperitoneal mass.

    PubMed

    Takesh, Mustafa; Zechmann, Christian M; Haufe, Sabine; Giesel, Frederik L; Kratochwil, Clemens

    2011-01-01

    Liposarcoma frequently occurs in the retroperitoneum and lower extremities, accounting for 20% of all mesenchymal malignancies. Liposarcomas vary by histology and can be classified into four types. Those four types are well differentiated, myxoid/round cell, pleomorphic and dedifferentiated. Due to retroperitoneal location of this tumor, it is expected to affect the kidney position. Renography has provided a unique tool for noninvasive evaluation of various functional parameters e.g. relative renal function. Most renography studies are carried out using the posterior view, under the assumption that the depths of both kidneys are similar so that the radiotracer counts in the region of interest will be attenuated to the same extent. Errors in estimation of the relative renal function may arise if the kidneys are at different depths e.g. secondary to a pushing tumor. Geometric mean imaging from combined anterior and posterior views helps to overcome this issue. This case shows the impact of geometric mean imaging in the truthful determination of partial function in patients with retroperitoneal liposarcoma.

  14. The accuracy with which the 5 times sit-to-stand test, versus gait speed, can identify poor exercise tolerance in patients with COPD

    PubMed Central

    Bernabeu-Mora, Roberto; Medina-Mirapeix, Francesc; Llamazares-Herrán, Eduardo; de Oliveira-Sousa, Silvana Loana; Sánchez-Martinez, Mª Piedad; Escolar-Reina, Pilar

    2016-01-01

    Abstract Identifying those patients who underperform in the 6-minute walk test (6MWT <350 m), and the reasons for their poor performance, is a major concern in the management of chronic obstructive pulmonary disease. To explore the accuracy and relevance of the 4-m gait-speed (4MGS) test, and the 5-repetition sit-to-stand (5STS) test, as diagnostic markers, and clinical determinants, of poor performance in the 6MWT. We recruited 137 patients with stable chronic obstructive pulmonary disease to participate in our cross-sectional study. Patients completed the 4MGS and 5STS tests, with quantitative (in seconds) and qualitative ordinal data collected; the latter were categorized using a scale of 0 to 4. The following potential covariates and clinical determinants of poor 6MWT were collated: age, quadriceps muscle-strength (QMS), health status, dyspnea, depression, and airflow limitation. Area under the receiver-operating characteristic curve data (AUC) was used to assess accuracy, with logistic regression used to explore relevance as clinical determinants. The AUCs generated using the 4MGS and 5STS tests were comparable, at 0.719 (95% confidence interval [CI] 0.629–0.809) and 0.711 (95% CI 0.613–0.809), respectively. With ordinal data, the 5STS test was most accurate (AUC of 0.732; 95% CI 0.645–0.819); the 4MGS test showed poor discriminatory power (AUC <0.7), although accuracy improved (0.726, 95% CI 0.637–0.816) when covariates were included. Unlike the 4MGS test, the 5STS test provided a significant clinical determinant of a poor 6MWT (odds ratio 1.23, 95% CI 1.05–1.44). The 5STS test reliably predicts a poor 6MWT, especially when using ordinal data. Used alone, the 4MGS test is reliable when measured with continuous data. PMID:27583918

  15. BIOACCESSIBILITY TESTS ACCURATELY ESTIMATE ...

    EPA Pesticide Factsheets

    Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from five Pb-contaminated Superfund sites had relative bioavailabilities from 33%-63%, with a mean of about 50%. Treatment of two of the soils with P significantly reduced the bioavailability of Pb. The bioaccessibility of the Pb in the test soils was then measured in six in vitro tests and regressed on bioavailability. They were: the “Relative Bioavailability Leaching Procedure” (RBALP) at pH 1.5, the same test conducted at pH 2.5, the “Ohio State University In vitro Gastrointestinal” method (OSU IVG), the “Urban Soil Bioaccessible Lead Test”, the modified “Physiologically Based Extraction Test” and the “Waterfowl Physiologically Based Extraction Test.” All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the RBALP pH 2.5 and OSU IVG tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter 24%, or present as Pb sulfate 18%. Ad

  16. Accurate spectral color measurements

    NASA Astrophysics Data System (ADS)

    Hiltunen, Jouni; Jaeaeskelaeinen, Timo; Parkkinen, Jussi P. S.

    1999-08-01

    Surface color measurement is of importance in a very wide range of industrial applications including paint, paper, printing, photography, textiles, plastics and so on. For a demanding color measurements spectral approach is often needed. One can measure a color spectrum with a spectrophotometer using calibrated standard samples as a reference. Because it is impossible to define absolute color values of a sample, we always work with approximations. The human eye can perceive color difference as small as 0.5 CIELAB units and thus distinguish millions of colors. This 0.5 unit difference should be a goal for the precise color measurements. This limit is not a problem if we only want to measure the color difference of two samples, but if we want to know in a same time exact color coordinate values accuracy problems arise. The values of two instruments can be astonishingly different. The accuracy of the instrument used in color measurement may depend on various errors such as photometric non-linearity, wavelength error, integrating sphere dark level error, integrating sphere error in both specular included and specular excluded modes. Thus the correction formulas should be used to get more accurate results. Another question is how many channels i.e. wavelengths we are using to measure a spectrum. It is obvious that the sampling interval should be short to get more precise results. Furthermore, the result we get is always compromise of measuring time, conditions and cost. Sometimes we have to use portable syste or the shape and the size of samples makes it impossible to use sensitive equipment. In this study a small set of calibrated color tiles measured with the Perkin Elmer Lamda 18 and the Minolta CM-2002 spectrophotometers are compared. In the paper we explain the typical error sources of spectral color measurements, and show which are the accuracy demands a good colorimeter should have.

  17. Functional characterization of CDK5 and CDK5R1 mutations identified in patients with non-syndromic intellectual disability.

    PubMed

    Moncini, Silvia; Castronovo, Paola; Murgia, Alessandra; Russo, Silvia; Bedeschi, Maria Francesca; Lunghi, Marta; Selicorni, Angelo; Bonati, Maria Teresa; Riva, Paola; Venturin, Marco

    2016-04-01

    Cyclin-dependent kinase 5 (CDK5) and cyclin-dependent kinase 5, regulatory subunit 1 (CDK5R1), encoding CDK5 activator p35, have a fundamental role in central nervous system (CNS) development and function, and are involved in the pathogenesis of several neurodegenerative disorders, thus constituting strong candidate genes for the onset of intellectual disability (ID). We carried out a mutation screening of CDK5 and CDK5R1 coding regions and CDK5R1 3'-UTR on a cohort of 360 patients with non-syndromic ID (NS-ID) using denaturing high performance liquid chromatography (DHPLC) and direct sequencing. We found one novel silent mutation in CDK5 and one novel silent mutation in CDK5R1 coding regions, three novel intronic variations in CDK5, not causing any splicing defect, and four novel heterozygous variations in CDK5R1 3'-UTR. None of these variations was present in 450 healthy controls and single-nucleotide polymorphism (SNP) databases. The functional study of CDK5R1 p.A108V mutation evidenced an impaired p35 cleavage by the calcium-dependent protease calpain. Moreover, luciferase constructs containing the CDK5R1 3'-UTR mutations showed altered gene expression levels. Eight known polymorphisms were also identified displaying different frequencies in NS-ID patients compared with the controls. In particular, the minor allele of CDK5R1 3'-UTR rs735555 polymorphism was associated with increased risk for NS-ID. In conclusion, our data suggest that mutations and polymorphisms in CDK5 and CDK5R1 genes may contribute to the onset of the NS-ID phenotype.

  18. Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients

    PubMed Central

    Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V.; Hacker, Neville F.; Jacob, Francis; Heinzelmann-Schwarz, Viola

    2016-01-01

    Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2–6 vs. α2–3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers. PMID:27764122

  19. Early Lung Function Testing in Infants with Aortic Arch Anomalies Identifies Patients at Risk for Airway Obstruction

    PubMed Central

    Roehr, Charles Christoph; Wilitzki, Silke; Opgen-Rhein, Bernd; Kalache, Karim; Proquitté, Hans; Bührer, Christoph; Schmalisch, Gerd

    2011-01-01

    Background Aortic arch anomalies (AAA) are rare cardio-vascular anomalies. Right-sided and double-sided aortic arch anomalies (RAAA, DAAA) are distinguished, both may cause airway obstructions. We studied the degree of airway obstruction in infants with AAA by neonatal lung function testing (LFT). Patients and Methods 17 patients (10 RAAA and 7 DAAA) with prenatal diagnosis of AAA were investigated. The median (range) post conception age at LFT was 40.3 (36.6–44.1) weeks, median body weight 3400 (2320–4665) g. Measurements included tidal breathing flow-volume loops (TBFVL), airway resistance (Raw) by bodyplethysmography and the maximal expiratory flow at functional residual capacity (V′maxFRC) by rapid thoracic-abdominal compression (RTC) technique. V′maxFRC was also expressed in Z-scores, based on published gender-, age and height-specific reference values. Results Abnormal lung function tests were seen in both RAAA and DAAA infants. Compared to RAAA infants, infants with DAAA had significantly more expiratory flow limitations in the TBFVL, (86% vs. 30%, p<0.05) and a significantly increased Raw (p = 0.015). Despite a significant correlation between Raw and the Z-score of V′maxFRC (r = 0.740, p<0.001), there were no statistically significant differences in V′maxFRC and it's Z-scores between RAAA and DAAA infants. 4 (24%) infants (2 RAAA, 2 DAAA) were near or below the 10th percentile of V′maxFRC, indicating a high risk for airway obstruction. Conclusion Both, infants with RAAA and DAAA, are at risk for airway obstruction and early LFT helps to identify and to monitor these infants. This may support the decision for therapeutic interventions before clinical symptoms arise. PMID:21966379

  20. Serum lipid alterations identified in chronic hepatitis B, hepatitis B virus-associated cirrhosis and carcinoma patients

    PubMed Central

    Wu, Tao; Zheng, Xiaojiao; Yang, Ming; Zhao, Aihua; Li, Meng; Chen, Tianlu; Panee, Jun; Jia, Wei; Ji, Guang

    2017-01-01

    The incidences of chronic hepatitis B (CHB), Hepatitis B virus (HBV)-associated cirrhosis and HBV-associated carcinoma are high and increasing. This study was designed to evaluate serum lipid metabolite changes that are associated with the progression from CHB to HBV-associated cirrhosis and ultimately to HBV-associated HCC. A targeted metabolomic assay was performed in fasting sera from 136 CHB patients, 104 HBV-associated cirrhosis, and 95 HBV-associated HCC using ultra-performance liquid chromatography triple quadrupole mass spectrometry. A total of 140 metabolites were identified. Clear separations between each two groups were obtained using the partial least squares discriminate analysis of 9 lipid metabolites. Progressively lower levels of long-chain lysophosphatidylcholines (lysoPC a C18:2, lysoPC a C20:3, lysoPC a C20:4) were observed from CHB to cirrhosis to carcinoma; lower levels of lysoPC a C20:4 were found in patients with higher model for end-stage liver disease in the same disease group; and lysoPC a C20:3 levels were lower in Child-Pugh Class C than in Class A and Class B in HBV-associated cirrhosis and HBV-associated HCC groups. The octadecadienyl carnitine level was higher in HBV-associated cirrhosis group than in other two groups. Serum levels of selected long-chain lysoPCs are promising markers for the progression of HBV-associated liver diseases. PMID:28198443

  1. Plasma Amino Acid Profiling Identifies Specific Amino Acid Associations with Cardiovascular Function in Patients with Systolic Heart Failure

    PubMed Central

    Hakuno, Daihiko; Hamba, Yasuhito; Toya, Takumi; Adachi, Takeshi

    2015-01-01

    with flow-mediated dilatation (p < 0.05). Conclusions Plasma AA profiling identified correlations of specific AAs with cardiac function and concomitant factors, highlighting the cardio-hepatic-skeletal muscle axis in patients with systolic HF. PMID:25658112

  2. A point process approach to identifying and tracking transitions in neural spiking dynamics in the subthalamic nucleus of Parkinson's patients

    NASA Astrophysics Data System (ADS)

    Deng, Xinyi; Eskandar, Emad N.; Eden, Uri T.

    2013-12-01

    Understanding the role of rhythmic dynamics in normal and diseased brain function is an important area of research in neural electrophysiology. Identifying and tracking changes in rhythms associated with spike trains present an additional challenge, because standard approaches for continuous-valued neural recordings—such as local field potential, magnetoencephalography, and electroencephalography data—require assumptions that do not typically hold for point process data. Additionally, subtle changes in the history dependent structure of a spike train have been shown to lead to robust changes in rhythmic firing patterns. Here, we propose a point process modeling framework to characterize the rhythmic spiking dynamics in spike trains, test for statistically significant changes to those dynamics, and track the temporal evolution of such changes. We first construct a two-state point process model incorporating spiking history and develop a likelihood ratio test to detect changes in the firing structure. We then apply adaptive state-space filters and smoothers to track these changes through time. We illustrate our approach with a simulation study as well as with experimental data recorded in the subthalamic nucleus of Parkinson's patients performing an arm movement task. Our analyses show that during the arm movement task, neurons underwent a complex pattern of modulation of spiking intensity characterized initially by a release of inhibitory control at 20-40 ms after a spike, followed by a decrease in excitatory influence at 40-60 ms after a spike.

  3. Identifying the symptom and functional domains in patients with fibromyalgia: results of a cross-sectional Internet-based survey in Italy

    PubMed Central

    Salaffi, Fausto; Mozzani, Flavio; Draghessi, Antonella; Atzeni, Fabiola; Catellani, Rosita; Ciapetti, Alessandro; Di Carlo, Marco; Sarzi-Puttini, Piercarlo

    2016-01-01

    Objective The aims of this cross-sectional study were to investigate the usefulness of using an Internet survey of patients with fibromyalgia in order to obtain information concerning symptoms and functionality and identify clusters of clinical features that can distinguish patient subsets. Methods An Internet website has been used to collect data. Fibromyalgia Impact Questionnaire Revised version, self-administered Fibromyalgia Activity Score, and Self-Administered Pain Scale were used as questionnaires. Hierarchical agglomerative clustering was applied to the data obtained in order to identify symptoms and functional-based subgroups. Results Three hundred and fifty-three patients completed the study (85.3% women). The highest scored items were those related to sleep quality, fatigue/energy, pain, stiffness, degree of tenderness, balance problems, and environmental sensitivity. A high proportion of patients reported pain in the neck (81.4%), upper back (70.1%), and lower back (83.2%). A three-cluster solution best fitted the data. The variables were significantly different (P<0.0001) among the three clusters: cluster 1 (117 patients) reflected the lowest average scores across all symptoms, cluster 3 (116 patients) the highest scores, and cluster 2 (120 patients) captured moderate symptom levels, with low depression and anxiety. Conclusion Three subgroups of fibromyalgia samples in a large cohort of patients have been identified by using an Internet survey. This approach could provide rationale to support the study of individualized clinical evaluation and may be used to identify optimal treatment strategies. PMID:27257392

  4. The role of technetium-99m stannous pyrophosphate in myocardial imaging to recognize, localize and identify extension of acute myocardial infarction in patients

    NASA Technical Reports Server (NTRS)

    Willerson, J. T.; Parkey, R. W.; Bonte, F. J.; Stokely, E. M.; Buja, E. M.

    1975-01-01

    The ability of technetium-99m stannous pyrophosphate myocardial scintigrams to aid diagnostically in recognizing, localizing, and identifying extension of acute myocardial infarction in patients was evaluated. The present study is an extension of previous animal and patient evaluations that were recently performed utilizing this myocardial imaging agent.

  5. Genome Wide Association Study to Identify SNPs and CNPs Associated with Development of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

    DTIC Science & Technology

    2012-10-01

    Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Development of Erectile Dysfunction Following...32 A Two-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Change in American Urological...of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate

  6. Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers

    PubMed Central

    Bradford, James R.; Wappett, Mark; Beran, Garry; Logie, Armelle; Delpuech, Oona; Brown, Henry; Boros, Joanna; Camp, Nicola J.; McEwen, Robert; Mazzola, Anne Marie; D'Cruz, Celina; Barry, Simon T.

    2016-01-01

    The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX). Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type. This implies heterogeneous recruitment of mouse stroma to the xenograft independent of tumor type. We then generate cross-species expression networks to recapitulate a known association between tumor epithelial cells and fibroblast activation, and propose a potentially novel relationship between two hypoxia-associated genes, human MIF and mouse Ddx6. Assessment of disease subtype also reveals MMP12 as a putative stromal marker of triple-negative breast cancer. Finally, we establish that our ability to dissect recruited stroma from trans-differentiated tumor cells is crucial to identifying stem-like poor-prognosis signatures in the tumor compartment. In conclusion, RNA-Seq is a powerful, cost-effective solution to global analysis of human tumor and mouse stroma simultaneously, providing new insights into mouse stromal heterogeneity and compartment-specific disease markers that are otherwise overlooked by alternative technologies. The study represents the first comprehensive analysis of its kind across multiple PDX models, and supports adoption of the approach in pre-clinical drug efficacy studies, and compartment-specific biomarker discovery. PMID:26980748

  7. Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers.

    PubMed

    Bradford, James R; Wappett, Mark; Beran, Garry; Logie, Armelle; Delpuech, Oona; Brown, Henry; Boros, Joanna; Camp, Nicola J; McEwen, Robert; Mazzola, Anne Marie; D'Cruz, Celina; Barry, Simon T

    2016-04-12

    The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX).Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type. This implies heterogeneous recruitment of mouse stroma to the xenograft independent of tumor type. We then generate cross-species expression networks to recapitulate a known association between tumor epithelial cells and fibroblast activation, and propose a potentially novel relationship between two hypoxia-associated genes, human MIF and mouse Ddx6. Assessment of disease subtype also reveals MMP12 as a putative stromal marker of triple-negative breast cancer. Finally, we establish that our ability to dissect recruited stroma from trans-differentiated tumor cells is crucial to identifying stem-like poor-prognosis signatures in the tumor compartment.In conclusion, RNA-Seq is a powerful, cost-effective solution to global analysis of human tumor and mouse stroma simultaneously, providing new insights into mouse stromal heterogeneity and compartment-specific disease markers that are otherwise overlooked by alternative technologies. The study represents the first comprehensive analysis of its kind across multiple PDX models, and supports adoption of the approach in pre-clinical drug efficacy studies, and compartment-specific biomarker discovery.

  8. Identifying unmet informational needs in the inpatient setting to increase patient and caregiver engagement in the context of pediatric hematopoietic stem cell transplantation

    PubMed Central

    Kaziunas, Elizabeth; Hanauer, David A; Ackerman, Mark S

    2016-01-01

    Background Patient-centered care has been shown to improve patient outcomes, satisfaction, and engagement. However, there is a paucity of research on patient-centered care in the inpatient setting, including an understanding of unmet informational needs that may be limiting patient engagement. Pediatric hematopoietic stem cell transplantation (HSCT) represents an ideal patient population for elucidating unmet informational needs, due to the procedure’s complexity and its requirement for caregiver involvement. Methods We conducted field observations and semi-structured interviews of pediatric HSCT caregivers and patients to identify informational challenges in the inpatient hospital setting. Data were analyzed using a thematic grounded theory approach. Results Three stages of the caregiving experience that could potentially be supported by a health information technology system, with the goal of enhancing patient/caregiver engagement, were identified: (1) navigating the health system and learning to communicate effectively with the healthcare team, (2) managing daily challenges of caregiving, and (3) transitioning from inpatient care to long-term outpatient management. Discussion We provide four practical recommendations to meet the informational needs of pediatric HSCT patients and caregivers: (1) provide patients/caregivers with real-time access to electronic health record data, (2) provide information about the clinical trials in which the patient is enrolled, (3) provide information about the patient’s care team, and (4) properly prepare patients and caregivers for hospital discharge. Conclusion Pediatric HSCT caregivers and patients have multiple informational needs that could be met with a health information technology system that integrates data from several sources, including electronic health records. Meeting these needs could reduce patients’ and caregivers’ anxiety surrounding the care process; reduce information asymmetry between caregivers/patients

  9. Roles of the Wada Test and Functional Magnetic Resonance Imaging in Identifying the Language-dominant Hemisphere among Patients with Gliomas Located near Speech Areas.

    PubMed

    Ishikawa, Tatsuya; Muragaki, Yoshihiro; Maruyama, Takashi; Abe, Kayoko; Kawamata, Takakazu

    2017-01-15

    This study examined the accuracy of functional magnetic resonance imaging (fMRI) in identifying the language-dominant hemisphere and the situations in which the Wada test can be skipped among patients with gliomas located near speech areas. We examined 74 patients [48 men (64.9%); mean ± standard deviation age of 42.7 ± 13.6 years (range: 13 to 70 years); 71 right-handed, 2 left-handed, and 1 ambidextrous] with gliomas located near speech areas. All patients underwent the Wada test and fMRI, and 34 patients underwent awake surgery. The "last-and-first" task was administered during fMRI. The Wada test was successful in determining the language-dominant hemisphere in 73 patients (98.6%): left hemisphere in 68 patients (91.9%), right hemisphere in 4 patients (5.4%), and bilateral in 1 patient (1.4%). The dominant hemisphere for right-handed patients (n = 71) was the left hemisphere in 67 patients (94.3%), right hemisphere in 3 patients (4.2%), and undetectable in 1 patient (1.4%). The fMRI was successful in determining the language-dominant hemisphere in 53 patients (71.6%). The results of the Wada test and fMRI were inconsistent in 5 patients (8.6%), of which 3 (5.2%) exhibited dominance in opposite hemispheres. Furthermore, 2 of these 3 cases (2.7%) were contralateral false positive cases, whereby fMRI identified the right-hemisphere as language dominant for right-handed individuals with tumors in the left hemisphere. Based on these findings, we concluded that the Wada test can be skipped if language dominancy can be detected by fMRI.

  10. Roles of the Wada Test and Functional Magnetic Resonance Imaging in Identifying the Language-dominant Hemisphere among Patients with Gliomas Located near Speech Areas

    PubMed Central

    ISHIKAWA, Tatsuya; MURAGAKI, Yoshihiro; MARUYAMA, Takashi; ABE, Kayoko; KAWAMATA, Takakazu

    2017-01-01

    This study examined the accuracy of functional magnetic resonance imaging (fMRI) in identifying the language-dominant hemisphere and the situations in which the Wada test can be skipped among patients with gliomas located near speech areas. We examined 74 patients [48 men (64.9%); mean ± standard deviation age of 42.7 ± 13.6 years (range: 13 to 70 years); 71 right-handed, 2 left-handed, and 1 ambidextrous] with gliomas located near speech areas. All patients underwent the Wada test and fMRI, and 34 patients underwent awake surgery. The “last-and-first” task was administered during fMRI. The Wada test was successful in determining the language-dominant hemisphere in 73 patients (98.6%): left hemisphere in 68 patients (91.9%), right hemisphere in 4 patients (5.4%), and bilateral in 1 patient (1.4%). The dominant hemisphere for right-handed patients (n = 71) was the left hemisphere in 67 patients (94.3%), right hemisphere in 3 patients (4.2%), and undetectable in 1 patient (1.4%). The fMRI was successful in determining the language-dominant hemisphere in 53 patients (71.6%). The results of the Wada test and fMRI were inconsistent in 5 patients (8.6%), of which 3 (5.2%) exhibited dominance in opposite hemispheres. Furthermore, 2 of these 3 cases (2.7%) were contralateral false positive cases, whereby fMRI identified the right-hemisphere as language dominant for right-handed individuals with tumors in the left hemisphere. Based on these findings, we concluded that the Wada test can be skipped if language dominancy can be detected by fMRI. PMID:27980284

  11. Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis.

    PubMed

    Cunningham, Janet L; Grimelius, Lars; Sundin, Anders; Agarwal, Smriti; Janson, Eva T

    2007-01-01

    Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, ppatients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index >/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

  12. The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

    PubMed Central

    Silva, Bruna Daniella Souza; Tannus-Silva, Daniela Graner Schuwartz; Rabahi, Marcelo Fouad; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2013-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world’s population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients. PMID:24626307

  13. Health service pathways for patients with chronic leg ulcers: identifying effective pathways for facilitation of evidence based wound care

    PubMed Central

    2013-01-01

    Background Chronic leg ulcers cause long term ill-health for older adults and the condition places a significant burden on health service resources. Although evidence on effective management of the condition is available, a significant evidence-practice gap is known to exist, with many suggested reasons e.g. multiple care providers, costs of care and treatments. This study aimed to identify effective health service pathways of care which facilitated evidence-based management of chronic leg ulcers. Methods A sample of 70 patients presenting with a lower limb leg or foot ulcer at specialist wound clinics in Queensland, Australia were recruited for an observational study and survey. Retrospective data were collected on demographics, health, medical history, treatments, costs and health service pathways in the previous 12 months. Prospective data were collected on health service pathways, pain, functional ability, quality of life, treatments, wound healing and recurrence outcomes for 24 weeks from admission. Results Retrospective data indicated that evidence based guidelines were poorly implemented prior to admission to the study, e.g. only 31% of participants with a lower limb ulcer had an ABPI or duplex assessment in the previous 12 months. On average, participants accessed care 2–3 times/week for 17 weeks from multiple health service providers in the twelve months before admission to the study clinics. Following admission to specialist wound clinics, participants accessed care on average once per week for 12 weeks from a smaller range of providers. The median ulcer duration on admission to the study was 22 weeks (range 2–728 weeks). Following admission to wound clinics, implementation of key indicators of evidence based care increased (p < 0.001) and Kaplan-Meier survival analysis found the median time to healing was 12 weeks (95% CI 9.3–14.7). Implementation of evidence based care was significantly related to improved healing outcomes (p < 0

  14. Accurate ab Initio Spin Densities.

    PubMed

    Boguslawski, Katharina; Marti, Konrad H; Legeza, Ors; Reiher, Markus

    2012-06-12

    We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as a basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys.2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insight into chemically interesting features of the molecule under study such as the distribution of α and β electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput.2011, 7, 2740].

  15. Implementation of Predictive Data Mining Techniques for Identifying Risk Factors of Early AVF Failure in Hemodialysis Patients

    PubMed Central

    Rezapour, Mohammad; Khavanin Zadeh, Morteza; Sepehri, Mohammad Mehdi

    2013-01-01

    Arteriovenous fistula (AVF) is an important vascular access for hemodialysis (HD) treatment but has 20–60% rate of early failure. Detecting association between patient's parameters and early AVF failure is important for reducing its prevalence and relevant costs. Also predicting incidence of this complication in new patients is a beneficial controlling procedure. Patient safety and preservation of early AVF failure is the ultimate goal. Our research society is Hasheminejad Kidney Center (HKC) of Tehran, which is one of Iran's largest renal hospitals. We analyzed data of 193 HD patients using supervised techniques of data mining approach. There were 137 male (70.98%) and 56 female (29.02%) patients introduced into this study. The average of age for all the patients was 53.87 ± 17.47 years. Twenty eight patients had smoked and the number of diabetic patients and nondiabetics was 87 and 106, respectively. A significant relationship was found between “diabetes mellitus,” “smoking,” and “hypertension” with early AVF failure in this study. We have found that these mentioned risk factors have important roles in outcome of vascular surgery, versus other parameters such as “age.” Then we predicted this complication in future AVF surgeries and evaluated our designed prediction methods with accuracy rates of 61.66%–75.13%. PMID:23861725

  16. Automated Analysis of Vital Signs to Identify Patients with Substantial Bleeding before Hospital Arrival: A Feasibility Study

    DTIC Science & Technology

    2015-05-01

    activating the cardiac catheterization team when the prehospital ECG shows ST-elevation myocardial infarction in a patient with chest pain illustrates...this article is prohibited. to reduce door-to-balloon times for patients with ST-segment elevation myocar- dial infarction undergoing primary

  17. Patient Education: Identifying Risks and Self-Management Approaches for Adherence and Sudden Unexpected Death in Epilepsy.

    PubMed

    Shafer, Patricia Osborne; Buchhalter, Jeffrey

    2016-05-01

    Patient education in epilepsy is one part of quality epilepsy care and is an evolving and growing field. Health outcomes, patient satisfaction, safety, patient/provider communication, and quality of life may all be affected by what people are taught (or not taught), what they understand, and how they use this information to make decisions and manage their health. Data regarding learning needs and interventions to address medication adherence and sudden unexpected death in epilepsy education can be used to guide clinicians in health care or community settings.

  18. Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

    PubMed Central

    Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

    2015-01-01

    Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional

  19. Novel germline mutations in FLCN gene identified in two Chinese patients with Birt-Hogg-Dubé syndrome.

    PubMed

    Li, Teng; Ning, Xianghui; He, Qun; Gong, Kan

    2017-01-09

    Birt-Hogg-Dubé (BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin (FLCN) gene, is characterized by the presence of fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma (RCC). Few BHD syndrome cases have been reported in Asian countries, and cutaneous presentations are relatively rare in Asian patients. Asian BHD patients may be misdiagnosed due to their atypical manifestations. Here, we report two Chinese BHD patients with novel FLCN mutations (c.946-947delAG in exon 9 and c.770-772delCCT in exon 7). Both of them had RCC and spontaneous pneumothorax without fibrofolliculomas. In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts (pneumothorax).

  20. Novel, In-House, SYBR Green Based One-Step rRT-PCR: Rapid and Accurate Diagnosis of Crimean-Congo Hemorrhagic Fever Virus in Suspected Patients From Iran

    PubMed Central

    Zahraei, Bentolhoda; Hashemzadeh, Mohammad Sadegh; Najarasl, Mohammad; Zahiriyeganeh, Samaneh; Tat, Mahdi; Metanat, Maliheh; Sepehri Rad, Nahid; Khansari-nejad, Behzad; Zafari, Ehsan; Sharti, Mojtaba; Dorostkar, Ruhollah

    2016-01-01

    Background The Crimean-Congo hemorrhagic fever (CCHF) virus causes severe disease in humans, with a high mortality rate. Since, there is no approved vaccine or specific treatment for CCHF, an early and accurate diagnosis, as well as reliable surveillance, is essential for case management and patient improvement. Objectives For this research, our aim was to evaluate the application of a novel SYBR Green based one-step real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay for the in-house diagnosis of the CCHF virus. Patients and Methods In this experimental study, the highly conserved S-region sequence of the CCHF viral genome was first adapted from GenBank, and the specific primers targeting this region were designed. Then, the viral RNA was extracted from 75 serum samples from different patients in eastern Iran. The sensitivity and specificity of the primers were also evaluated in positive serum samples previously confirmed to have the CCHF virus, by this one-step rRT-PCR assay, as well as a DNA sequencing analysis. Results From a total of 75 suspected serum samples, 42 were confirmed to be positive for CCHF virus, with no false-positives detected by the sequencing results. After 40 amplification cycles, the melting curve analysis revealed a mean melting temperature (Tm) of 86.5 ± 0.6°C (quite different from those of the primer-dimers), and the positive samples showed only a small variation in the parameters. In all of the positive samples, the predicted length of 420 bp was confirmed by electrophoresis. Moreover, the sensitivity test showed that this assay can detect less than 20 copies of viral RNA per reaction. Conclusions This study showed that this novel one-step rRT-PCR assay is a rapid, reliable, repeatable, specific, sensitive, and simple tool for the detection of the CCHF virus. PMID:27099688

  1. Unique characteristics of cryptococcosis identified after death in patients with liver cirrhosis: comparison with concurrent cohort diagnosed antemortem.

    PubMed

    Singh, Nina; Sifri, Costi D; Silveira, Fernanda P; Miller, Rachel; Gregg, Kevin S; Huprikar, Shirish; Lease, Erika D; Zimmer, Andrea; Dummer, J Stephen; Spak, Cedric W; Koval, Christine; Banach, David B; Shroff, Miloni; Le, Jade; Ostrander, Darin; Avery, Robin; Eid, Albert; Razonable, Raymund R; Montero, Jose; Blumberg, Emily; Alynbiawi, Ahlaam; Morris, Michele I; Randall, Henry B; Alangaden, George; Tessier, Jeffrey; Cacciarelli, Thomas V; Wagener, Marilyn M; Sun, Hsin Yun

    2016-09-06

    Characteristics of cirrhosis-associated cryptococcosis first diagnosed after death are not fully known. In a multicenter study, data generated as standard of care was systematically collected in 113 consecutive patients with cirrhosis and cryptococcosis followed for 80 patient-years. The diagnosis of cryptococcosis was first established after death in 15.9% (18/113) of the patients. Compared to cases diagnosed while alive, these patients had higher MELD score (33 vs. 22, P = .029) and higher rate of cryptococcemia (75.0% vs. 41.9%, P = .027). Cases diagnosed after death, in comparison to those diagnosed during life were more likely to present with shock (OR 3.42, 95% CI 1.18-9.90, P = .023), require mechanical ventilation at admission (OR 8.5, 95% CI 2.74-26.38, P = .001), less likely to undergo testing for serum cryptococcal antigen (OR 0.07, 95% CI 0.02-0.21, P < .001) and have positive antigen when the test was performed (OR 0.07, 95% CI 0.01-0.60, P = .016). In a subset of cirrhotic patients with advanced liver disease cryptococcosis was first recognized after death. These patients had the characteristics of presenting with fulminant fungemia, were less likely to have positive serum cryptococcal antigen and posed a diagnostic challenge for care providers.

  2. Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility

    PubMed Central

    Mattiello, Rita; Vidal, Paula Cristina; Sarria, Edgar Enrique; Pitrez, Paulo Márcio; Stein, Renato Tetelbom; Mocelin, Helena Teresinha; Fischer, Gilberto Bueno; Jones, Marcus Herbert; Pinto, Leonardo Araújo

    2016-01-01

    ABSTRACT Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications. PMID:27383929

  3. Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support

    PubMed Central

    2014-01-01

    Background Patients with rare diseases such as congenital hypogonadotropic hypogonadism (CHH) are dispersed, often challenged to find specialized care and face other health disparities. The internet has the potential to reach a wide audience of rare disease patients and can help connect patients and specialists. Therefore, this study aimed to: (i) determine if web-based platforms could be effectively used to conduct an online needs assessment of dispersed CHH patients; (ii) identify the unmet health and informational needs of CHH patients and (iii) assess patient acceptability regarding patient-centered, web-based interventions to bridge shortfalls in care. Methods A sequential mixed-methods design was used: first, an online survey was conducted to evaluate health promoting behavior and identify unmet health and informational needs of CHH men. Subsequently, patient focus groups were held to explore specific patient-identified targets for care and to examine the acceptability of possible online interventions. Descriptive statistics and thematic qualitative analyses were used. Results 105 male participants completed the online survey (mean age 37 ± 11, range 19–66 years) representing a spectrum of patients across a broad socioeconomic range and all but one subject had adequate healthcare literacy. The survey revealed periods of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%) exceeding one year. Patient focus groups identified lasting psychological effects related to feelings of isolation, shame and body-image concerns. Survey respondents were active internet users, nearly all had sought CHH information online (101/105, 96%), and they rated the internet, healthcare providers, and online community as equally important CHH information sources. Focus group participants were overwhelmingly positive regarding online interventions/support with links to reach expert healthcare providers and for peer-to-peer support. Conclusion The web

  4. Urinary free light chains may help to identify infection in patients with elevated systemic inflammation due to rheumatic disease.

    PubMed

    Bramlage, Carsten P; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Müller, Gerhard A; Koziolek, Michael

    2017-04-01

    The risk of infection in patients with rheumatic diseases is elevated, but a clear marker to differentiate the cause of the systemic inflammation is missing. We assessed the ability urinary immunoglobulin free light chains (FLCs) to indicate the presence of infection in patients with rheumatic disease. We performed a retrospective analysis of patients with rheumatic disease attending the Georg-August University Hospital in Goettingen, Germany, from January 2011 to December 2013. Subjects were included if they had urine levels of κ and λ FLCs available. A reference group of patients without autoimmune disease, but with documented infection, was constructed. A total of 1500 patients had their urinary FLCs quantified during the study period. Of the 382 patients with rheumatic disease, 172 (45%) displayed no systemic inflammation, 162 (42%) had inflammation due to the underlying disease activity, and 48 (13%) had inflammation due to a confirmed infection. Urinary FLC concentrations were much higher in patients with rheumatic diseases and infection (κ 68.8 ± 81.8 mg/L, λ 31.4 ± 53.5 mg/L) compared to those with inflammation due to rheumatic disease activity (κ 22.7 ± 26.3 mg/L, λ 8.1 ± 9.1 mg/L, κ p < 0.001, λ p = 0.004). Urinary κ FLCs demonstrated good ability to predict infection, with a sensitivity of 63% and specificity of 84%. Urinary λ FLCs gave similar values, with a sensitivity of 65% and specificity of 81%. FLCs may be useful for distinguishing inflammation due to rheumatic disease activity from that due to the additional presence of infection. The ability to quantify these proteins in urine provides a simple alternative to the use of blood.

  5. Does calprotectin level identify a subgroup among patients suffering from irritable bowel syndrome? Results of a prospective study

    PubMed Central

    Aziz, Moutaz; Aubry, Typhaine; Gourcerol, Guillaume; Quillard, Muriel; Zalar, Alberto; Coëffier, Moïse; Dechelotte, Pierre; Leroi, Anne-Marie; Ducrotté, Philippe

    2016-01-01

    Background Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated. Objective The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up. Methods Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn’s disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies. Results Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (P = 0.06), there were no other differences between the two groups. When elevated, calprotectin was correlated with age (P = 0.03, r = 0.22). Conclusions Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities. PMID:28344794

  6. Mycobacterium lentiflavum, a recently identified slow-growing mycobacterial species: clinical significance in immunosuppressed cancer patients and summary of reported cases of infection.

    PubMed

    Safdar, A; Han, X Y

    2005-08-01

    The clinical significance of Mycobacterium lentiflavum, a recently identified nontuberculous mycobacterium, remains uncertain, especially in immunosuppressed cancer patients. The records of all patients in whom M. lentiflavum was identified using a gene sequencing technique between January 2001 and December 2003 were reviewed. The mean age among 12 patients was 51+/-20 years, and 11 (92%) patients had a hematologic malignancy. Six of seven (86%) hematopoietic stem cell transplant recipients had received allogeneic donor grafts. Nine (75%) patients had predisposing risk factors for infection, seven (58%) had severe lymphocytopenia (<400 cells/microl), five (42%) were receiving systemic corticosteroid therapy, and three (25%) had acute graft-versus-host disease. Only 1 of the 12 (8%) patients had evidence of probable pulmonary M. lentiflavum infection. Six M. lentiflavum strains were initially misidentified as Mycobacterium simiae and Mycobacterium avium-intracellulare complex using traditional biochemical tests. Four M. lentiflavum isolates were tested for antimicrobial susceptibility; they were susceptible to isoniazid, ethambutol, clarithromycin, and amikacin, and resistant to rifampin. M. lentiflavum was not clinically significant, even in these severely immunosuppressed cancer patients.

  7. Identifying Perceived Barriers along the HIV Care Continuum: Findings from Providers, Peer Educators, and Observations of Provider-Patient Interactions in Ethiopia.

    PubMed

    Kulkarni, Sarah; Hoffman, Susie; Gadisa, Tsigereda; Melaku, Zenebe; Fantehun, Mesganaw; Yigzaw, Muluneh; El-Sadr, Wafaa; Remien, Robert; Tymejczyk, Olga; Nash, Denis; Elul, Batya

    2016-07-01

    Increasing the proportion of HIV-positive individuals who link promptly to and are retained in care remains challenging in sub-Saharan Africa, but little evidence is available from the provider perspective. In 4 Ethiopian health facilities, we (1) interviewed providers and peer educators about their perceptions of service delivery- and patient-level barriers and (2) observed provider-patient interactions to characterize content and interpersonal aspects of counseling. In interviews, providers and peer educators demonstrated empathy and identified nonacceptance of HIV status, anticipated stigma from unintended disclosure, and fear of antiretroviral therapy as patient barriers, and brusque counseling and insufficient counseling at provider-initiated testing sites as service delivery-related. However, observations from the same clinics showed that providers often failed to elicit patients' barriers to retention, making it unlikely these would be addressed during counseling. Training is needed to improve interpersonal aspects of counseling and ensure providers elicit and address barriers to HIV care experienced by patients.

  8. Noninherited maternal antigens identify acceptable HLA mismatches: benefit to patients and cost-effectiveness for cord blood banks.

    PubMed

    Van der Zanden, Henk G M; Van Rood, Jon J; Oudshoorn, Machteld; Bakker, Jack N A; Melis, Angelo; Brand, Anneke; Scaradavou, Andromachi; Rubinstein, Pablo

    2014-11-01

    Cord blood unit (CBU) transplantations to patients mismatched for only 1 HLA antigen, which is identical to the CBU noninherited maternal antigen (NIMA), are designated as having a 6/6 "virtual" NIMA-matched phenotype and have a prognosis similar to 6/6 inherited HLA-matched CBUs. Such virtual HLA phenotypes of CBUs can be created by replacing the inherited alleles with 1 or more NIMAs. Phenotypes of Dutch patients (n = 2020) were matched against the inherited and virtual HLA phenotypes of the National Cord Blood Program CBU file (with known NIMA, n = 6827). Inherited 6/6 matches were found for 11% of the patients. Including virtual phenotypes resulted in, overall, 19-fold more different phenotypes than were inherited, conferring 6/6 virtual matches for an additional 20% of the patients, whereas another 17% might benefit from CBUs with a 4/6 HLA match and 1 NIMA match (4/6 + 1NIMA or 5/6 virtual match). The elucidation of donors' maternal HLA phenotypes can provide significant numbers of 6/6 and 5/6 virtually matched CBUs to patients and is potentially cost effective.

  9. Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity

    PubMed Central

    Hoang, Long Truong; Tolfvenstam, Thomas; Ooi, Eng Eong; Khor, Chiea Chuen; Naim, Ahmand Nazri Mohamed; Ho, Eliza Xin Pei; Ong, Swee Hoe; Wertheim, Heiman F.; Fox, Annette; Van Vinh Nguyen, Chau; Nghiem, Ngoc My; Ha, Tuan Manh; Thi Ngoc Tran, Anh; Tambayah, Paul; Lin, Raymond; Sangsajja, Chariya; Manosuthi, Weerawat; Chuchottaworn, Chareon; Sansayunh, Piamlarp; Chotpitayasunondh, Tawee; Suntarattiwong, Piyarat; Chokephaibulkit, Kulkanya; Puthavathana, Pilaipan; de Jong, Menno D.; Farrar, Jeremy; van Doorn, H. Rogier; Hibberd, Martin Lloyd

    2014-01-01

    Background The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. Methodology/Principal Findings Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. Conclusion/Significances The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients. PMID:25365328

  10. ST-T isointegral analysis of exercise stress body surface mapping for identifying ischemic areas in patients with angina pectoris

    SciTech Connect

    Nakajima, T.; Kawakubo, K.; Toda, I.; Mashima, S.; Ohtake, T.; Iio, M.; Sugimoto, T.

    1988-05-01

    ST-T isointegral analysis of body surface mapping was used in an attempt to localize ischemic areas on exercise tests. In 28 patients with angina pectoris and 10 healthy subjects, body surface potential was recorded with 87 leads, and ST isopotential and ST-T isointegral maps were constructed. In all 10 healthy subjects, the basic pattern of the ST-T isointegral map showed no significant change after exercise. In 23 of 28 patients with angina pectoris (82%), alterations in the ST-T isointegral map after exercise were observed. They were divided into four types (anterior, inferoposterior, lateral, and global) according to the distribution of negative values, which were well correlated with the extent of ischemic area determined by thallium myocardial scintigraphy and coronary angiography. The postexercise ST-T isointegral map was normalized after administration of nitroglycerin in four of five patients. In five patients (18%) who did not show abnormalities on the postexercise ST-T isointegral map, the magnitude of maximal ST depression was significantly smaller than that observed in the other 23 patients with angina pectoris (0.14 vs 0.23 mV on the average, p less than 0.05). It was concluded that the exercise test with ST-T isointegral mapping is a new method for noninvasive detection of location and severity of ischemic regions.

  11. Identifying Network Perturbation in Cancer

    PubMed Central

    Logsdon, Benjamin A.; Gentles, Andrew J.; Lee, Su-In

    2016-01-01

    We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each gene is perturbed—having distinct regulator connectivity in the inferred gene-regulator dependencies between the disease and normal conditions. This approach has distinct advantages over existing methods. First, DISCERN infers conditional dependencies between candidate regulators and genes, where conditional dependence relationships discriminate the evidence for direct interactions from indirect interactions more precisely than pairwise correlation. Second, DISCERN uses a new likelihood-based scoring function to alleviate concerns about accuracy of the specific edges inferred in a particular network. DISCERN identifies perturbed genes more accurately in synthetic data than existing methods to identify perturbed genes between distinct states. In expression datasets from patients with acute myeloid leukemia (AML), breast cancer and lung cancer, genes with high DISCERN scores in each cancer are enriched for known tumor drivers, genes associated with the biological processes known to be important in the disease, and genes associated with patient prognosis, in the respective cancer. Finally, we show that DISCERN can uncover potential mechanisms underlying network perturbation by explaining observed epigenomic activity patterns in cancer and normal tissue types more accurately than alternative methods, based on the available epigenomic data from the ENCODE project. PMID:27145341

  12. p53 status identifies triple-negative breast cancer patients who do not respond to adjuvant chemotherapy.

    PubMed

    Coradini, Danila; Biganzoli, Elia; Ardoino, Ilaria; Ambrogi, Federico; Boracchi, Patrizia; Demicheli, Romano; Daidone, Maria Grazia; Moliterni, Angela

    2015-06-01

    Genomic analysis and protein expression assimilate triple-negative breast cancers (TNBC) with basal-like breast tumors. TNBCs, however, have proved to encompass also tumors with normal-like phenotype and known to have favorable prognosis and to respond to chemotherapy. In a recent paper, we have provided evidence that p53 status is able to subdivide TNBCs into two distinct subgroups with different outcome, and consistent with basal- and normal-like phenotypes. Based on this finding, we explored the contribution of p53 status in predicting the response to adjuvant CMF or CMF followed doxorubicin chemotherapy of a group of TNBC patients. Results indicated that TNBC patients with a p53-positive tumor had a shorter relapse-free and overall survival than patients carrying a p53-negative TNBC, corroborating our hypothesis about the relationship between TNBC phenotype (basal-like versus normal-like) and p53 status as predictor of response to anthracycline/CMF-based chemotherapy.

  13. When Crohn's Disease is in Remission, More Patients Complete Capsule Endoscopy Study But Less Lesions are Identified

    PubMed Central

    Tsibouris, Panagiotis; Periklis, Apostolopoulos; Chrissostomos, Kalantzis; Antonios, Zalonis; Panagiota, Mavrogianni; Erasmia, Vlachou; Georgios, Alexandrakis

    2013-01-01

    Background and Aims: Wireless capsule endoscopy (WCE) is used in Crohn's disease (CD) to define disease extent. We aimed to define WCE detection rate of small bowel ulcerative lesions and completion rate in CD patients. Patients and Methods: A total of 102 consecutive CD patients, who successfully passed patency capsule, were matched to 102 controls. WCE was performed in both patients (in acute phase and CD clinical remission) and controls. Results: Eighty-six (84%) controls versus 62 (61%) patients in the acute phase (P = 0.003) and 96 (94%) in remission (P = 0.02) completed WCE study. Gastric passing time was 48 ± 66 min in controls, 66 ± 82 min in CD acute phase (P = 0.03) and 30 ± 21 min in remission (P = 0.07). Small bowel passing time was 276 ± 78 min in controls, 299 ± 78 min in the acute phase of CD (P = 0.04) and 248 ± 89 min in remission (P = 0.01). Mean capsule endoscopy Crohn's disease activity index (CECDAI) score was 14 ± 6 in acute small bowel CD, 12 ± 7 in acute small-large bowel CD (P = 0.08) and 2 ± 2 in both CD types while in remission (P = 1.00). Small bowel ulcerative lesions in the acute phase were more frequently in distal small bowel. Aphthous ulcers were frequent a month after entering clinical remission and tend to disappear gradually later on. No ulcerative lesions were present in deep remission. Patency capsule is rather safe to exclude small bowel obstruction. Conclusions: (1) A high percentage of patients with active CD do not complete small bowel study with WCE. (2) Small bowel ulcerative lesions in clinical remission were less severe, although at least 6 months are needed in order for them to disappear. PMID:23481131

  14. One-Month Global Longitudinal Strain Identifies Patients Who Will Develop Pacing-Induced Left Ventricular Dysfunction over Time: The Pacing and Ventricular Dysfunction (PAVD) Study

    PubMed Central

    Ahmed, Fozia Zahir; Motwani, Manish; Cunnington, Colin; Kwok, Chun Shing; Fullwood, Catherine; Oceandy, Delvac; Fitchet, Alan; Goode, Grahame Kevin; Luckie, Matthew; Zaidi, Amir Masood; Khattar, Rajdeep; Mamas, Mamas Andreas

    2017-01-01

    Background Predicting which individuals will have a decline in left ventricular (LV) function after pacemaker implantation remains an important challenge. We investigated whether LV global longitudinal strain (GLS), measured by 2D speckle tracking strain echocardiography, can identify patients at risk of pacing-induced left ventricular dysfunction (PIVD) or pacing-induced cardiomyopathy (PICMP). Methods Fifty-five patients with atrioventricular block and preserved LV function underwent dual-chamber pacemaker implantation and were followed with serial transthoracic echocardiography for 12 months for the development of PIVD (defined as a reduction in LV ejection fraction (LVEF) ≥5 percentage points at 12 months) or PICMP (reduction in LVEF to <45%). Results At 12 months, 15 (27%) patients developed PIVD; of these, 4 patients developed PICMP. At one month, GLS was significantly lower in the 15 patients who subsequently developed PIVD, compared to those who did not (n = 40) (GLS -12.6 vs. -16.4 respectively; p = 0.022). When patients with PICMP were excluded, one month GLS was significantly reduced compared to baseline whereas LVEF was not. One-month GLS had high predictive accuracy for determining subsequent development of PIVD or PICMP (AUC = 0.80, optimal GLS threshold: <−14.5, sensitivity 82%, specificity 75%); and particularly PICMP (AUC = 0.86, optimal GLS threshold: <−13.5, sensitivity 100%, specificity 71%). Conclusions GLS is a novel predictor of decline in LV systolic function following pacemaker implantation, with the potential to identify patients at risk of PIVD before measurable changes in LVEF are apparent. GLS measured one month after implantation has high predictive accuracy for identifying patients who later develop PIVD or PICMP. PMID:28095413

  15. Identifying Patients Who Are Unsuitable for Accelerated Partial Breast Irradiation Using Three-dimensional External Beam Conformal Techniques

    SciTech Connect

    Shikama, Naoto; Nakamura, Naoki; Kunishima, Naoaki; Hatanaka, Shogo; Sekiguchi, Kenji

    2012-07-01

    Purpose: Several recent studies reported that severe late toxicities including soft-tissue fibrosis and fat necrosis are present in patients treated with accelerated partial breast irradiation (APBI) and that these toxicities are associated with the large volume of tissue targeted by high-dose irradiation. The present study was performed to clarify which patients are unsuitable for APBI to avoid late severe toxicities. Methods and Materials: Study subjects comprised 50 consecutive patients with Stage 0-II unilateral breast cancer who underwent breast-conserving surgery, and in whom five or six surgical clips were placed during surgery. All patients were subsequently replanned using three-dimensional conformal radiotherapy (3D-CRT) APBI techniques according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 and Radiation Therapy Oncology Group (RTOG) 0413 protocol. The beam arrangements included mainly noncoplanar four- or five-field beams using 6-MV photons alone. Results: Dose-volume histogram (DVH) constraints for normal tissues according to the NSABP/RTOG protocol were satisfied in 39 patients (78%). Multivariate analysis revealed that only long craniocaudal clip distance (CCD) was correlated with nonoptimal DVH constraints (p = 0.02), but that pathological T stage, anteroposterior clip distance (APD), site of ipsilateral breast (IB) (right/left), location of the tumor (medial/lateral), and IB reference volume were not. DVH constraints were satisfied in 20% of patients with a long CCD ({>=}5.5 cm) and 92% of those with a short CCD (p < 0.0001). Median IB reference volume receiving {>=}50% of the prescribed dose (IB-V{sub 50}) of all patients was 49.0% (range, 31.4-68.6). Multivariate analysis revealed that only a long CCD was correlated with large IB-V{sub 50} (p < 0.0001), but other factors were not. Conclusion: Patients with long CCDs ({>=}5.5 cm) might be unsuitable for 3D-CRT APBI because of nonoptimal DVH constraints and large IB

  16. Improved Oxygenation 24 Hours After Transition to Airway Pressure Release Ventilation or High-Frequency Oscillatory Ventilation Accurately Discriminates Survival in Immunocompromised Pediatric Patients With Acute Respiratory Distress Syndrome*

    PubMed Central

    Yehya, Nadir; Topjian, Alexis A.; Thomas, Neal J.; Friess, Stuart H.

    2014-01-01

    Objectives Children with an immunocompromised condition and requiring invasive mechanical ventilation have high risk of death. Such patients are commonly transitioned to rescue modes of non-conventional ventilation, including airway pressure release ventilation and high-frequency oscillatory ventilation, for acute respiratory distress syndrome refractory to conventional ventilation. Our aim was to describe our experience with airway pressure release ventilation and high-frequency oscillatory ventilation in children with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation and to identify factors associated with survival. Design Retrospective cohort study. Setting Tertiary care, university-affiliated PICU. Patients Sixty pediatric patients with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation transitioned to either airway pressure release ventilation or high-frequency oscillatory ventilation. Interventions None. Measurements and Main Results Demographic data, ventilator settings, arterial blood gases, oxygenation index, and Pao2/Fio2 were recorded before transition to either mode of nonconventional ventilation and at predetermined intervals after transition for up to 5 days. Mortality in the entire cohort was 63% and did not differ between patients transitioned to airway pressure release ventilation and high-frequency oscillatory ventilation. For both airway pressure release ventilation and high-frequency oscillatory ventilation, improvements in oxygenation index and Pao2/Fio2 at 24 hours expressed as a fraction of pretransition values (oxygenation index24/oxygenation indexpre and Pao2/Fio224/Pao2/FIO2pre) reliably discriminated nonsurvivors from survivors, with receiver operating characteristic areas under the curves between 0.89 and 0.95 (p for all curves < 0.001). Sensitivity-specificity analysis suggested that less than 15% reduction in

  17. Application of systematic coronary risk evaluation chart to identify chronic myeloid leukemia patients at risk of cardiovascular diseases during nilotinib treatment.

    PubMed

    Breccia, Massimo; Molica, Matteo; Zacheo, Irene; Serrao, Alessandra; Alimena, Giuliana

    2015-03-01

    atherosclerotic events at 48 months was 8.5 % (95 % CI, 4.55-14.07): None of the low-risk patients according to the SCORE chart experienced atherosclerotic events compared to 10 % in the moderate risk category and 29 % in the high risk (p = 0.002). Atherosclerotic-free survival was 100, 89, and 69 % in the low, moderate, and high-risk population, respectively (p = 0.001). SCORE chart evaluation at disease baseline could be a valid tool to identify patients at high risk of atherosclerotic events during nilotinib treatment.

  18. Using DRS during breast conserving surgery: identifying robust optical parameters and influence of inter-patient variation

    PubMed Central

    de Boer, Lisanne L.; Hendriks, Benno H. W.; van Duijnhoven, Frederieke; Peeters-Baas, Marie-Jeanne T. F. D. Vrancken; Van de Vijver, Koen; Loo, Claudette E.; Jóźwiak, Katarzyna; Sterenborg, Henricus J. C. M.; Ruers, Theo J. M.

    2016-01-01

    Successful breast conserving surgery consists of complete removal of the tumor while sparing healthy surrounding tissue. Despite currently available imaging and margin assessment tools, recognizing tumor tissue at a resection margin during surgery is challenging. Diffuse reflectance spectroscopy (DRS), which uses light for tissue characterization, can potentially guide surgeons to prevent tumor positive margins. However, inter-patient variation and changes in tissue physiology occurring during the resection might hamper this light-based technology. Here we investigate how inter-patient variation and tissue status (in vivo vs ex vivo) affect the performance of the DRS optical parameters. In vivo and ex vivo measurements of 45 breast cancer patients were obtained and quantified with an analytical model to acquire the optical parameters. The optical parameter representing the ratio between fat and water provided the best discrimination between normal and tumor tissue, with an area under the receiver operating characteristic curve of 0.94. There was no substantial influence of other patient factors such as menopausal status on optical measurements. Contrary to expectations, normalization of the optical parameters did not improve the discriminative power. Furthermore, measurements taken in vivo were not significantly different from the measurements taken ex vivo. These findings indicate that DRS is a robust technology for the detection of tumor tissue during breast conserving surgery. PMID:28018735

  19. A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients.

    PubMed

    Bandrés, Eva; Malumbres, Raquel; Cubedo, Elena; Honorato, Beatriz; Zarate, Ruth; Labarga, Alberto; Gabisu, Unai; Sola, Jesus Javier; García-Foncillas, Jesus

    2007-05-01

    The benefit of postoperative adjuvant chemotherapy in patients with Dukes' B colorectal cancer is still uncertain and its routine use is not recommended. The five-year relapse rate is approximately 25-40% and the identification of patients at high risk of recurrence would represent an important strategy for the use of adjuvant chemotherapy. We retrospectively analyzed gene expression profiles in frozen tumor specimens from patients with Dukes' B colorectal cancer by using high density oligonucleotide microarrays. Our results show a subset of 48 genes differentially expressed with an associated probability <0.001 in the t-test. Another statistical procedure based on the Fisher criterion resulted in 11 genes able to separate both groups. We selected the 8 genes present in both subsets. The differential expression of five genes (CHD2, RPS5, ZNF148, BRI3 and MGC23401) in colon cancer progression was confirmed by real-time PCR in an independent set of patients of Dukes' B and C stages.

  20. Low-temperature infiltration identified using infrared thermography in patients with subcutaneous edema revealed ultrasonographically: A case report.

    PubMed

    Oya, Maiko; Takahashi, Toshiaki; Tanabe, Hidenori; Oe, Makoto; Murayama, Ryoko; Yabunaka, Koichi; Matsui, Yuko; Sanada, Hiromi

    Infiltration is a frequent complication of infusion therapy. We previously demonstrated the usefulness of infrared thermography as an objective method of detecting infiltration in healthy people. However, whether thermography can detect infiltration in clinical settings remains unknown. Therefore, we report two cases where thermography was useful in detecting infiltration at puncture sites. In both cases, tissue changes were verified ultrasonographically. The patients were a 56-year-old male with cholangitis and a 76-year-old female with hepatoma. In both cases, infiltration symptoms such as swelling and erythema occurred one day after the insertion of a peripheral intravenous catheter. Thermographic images from both patients revealed low-temperature areas spreading from the puncture sites; however, these changes were not observed in other patients. The temperature difference between the low-temperature areas and their surrounding skin surface exceeded 1.0°C. Concurrently, ultrasound images revealed that tissues surrounding the vein had a cobblestone appearance, indicating edema. In both patients, subcutaneous tissue changes suggested infiltration and both had low-temperature areas spreading from the puncture sites. Thus, subcutaneous edema may indicate infusion leakage, resulting in a decrease in the temperature of the associated skin surface. These cases suggest that infrared thermography is an effective method of objectively and noninvasively detecting infiltration.

  1. Identification of Mycobacterium avium subsp. paratuberculosis in Biopsy Specimens from Patients with Crohn's Disease Identified by In Situ Hybridization

    PubMed Central

    Sechi, Leonardo A.; Manuela, Mura; Francesco, Tanda; Amelia, Lissia; Antonello, Solinas; Giovanni, Fadda; Stefania, Zanetti

    2001-01-01

    Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract of unknown etiology. We report on the presence of cell wall-deficient Mycobacterium avium subsp. paratuberculosis in 35 of 48 paraffin-embedded tissue specimens from 33 patients with Crohn's disease by in situ hybridization with IS900 as a probe. PMID:11724871

  2. Limitations of the Patient Health Questionnaire in Identifying Anxiety and Depression in Community Mental Health: Many Cases Are Undetected

    ERIC Educational Resources Information Center

    Eack, Shaun M.; Greeno, Catherine G.; Lee, Bong-Jae

    2006-01-01

    Objective: To determine the concordance between the Structured Clinical Interview for DSM-IV (SCID) and the Patient Health Questionnaire (PHQ) in diagnosing anxiety and depressive disorders. Method: Fifty women seeking psychiatric services for their children at two mental health centers in western Pennsylvania were assessed for anxiety and…

  3. Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype

    PubMed Central

    Zastrow, Diane B.; Zornio, Patricia A.; Dries, Annika; Kohler, Jennefer; Fernandez, Liliana; Waggott, Daryl; Walkiewicz, Magdalena; Eng, Christine M.; Manning, Melanie A.; Farrelly, Ellyn; Fisher, Paul G.; Ashley, Euan A.; Bernstein, Jonathan A.

    2017-01-01

    Here we describe a patient who presented with a history of congenital diaphragmatic hernia, inguinal hernia, and recurrent umbilical hernia. She also has joint laxity, hypotonia, and dysmorphic features. A unifying diagnosis was not identified based on her clinical phenotype. As part of her evaluation through the Undiagnosed Diseases Network, trio whole-exome sequencing was performed. Pathogenic variants in FBN1 and TRPS1 were identified as causing two distinct autosomal dominant conditions, each with de novo inheritance. Fibrillin 1 (FBN1) mutations are associated with Marfan syndrome and a spectrum of similar phenotypes. TRPS1 mutations are associated with trichorhinophalangeal syndrome types I and III. Features of both conditions are evident in the patient reported here. Discrepant features of the conditions (e.g., stature) and the young age of the patient may have made a clinical diagnosis more difficult in the absence of exome-wide genetic testing. PMID:28050602

  4. Exome sequencing identifies de novo pathogenic variants in FBN1 and TRPS1 in a patient with a complex connective tissue phenotype.

    PubMed

    Zastrow, Diane B; Zornio, Patricia A; Dries, Annika; Kohler, Jennefer; Fernandez, Liliana; Waggott, Daryl; Walkiewicz, Magdalena; Eng, Christine M; Manning, Melanie A; Farrelly, Ellyn; Fisher, Paul G; Ashley, Euan A; Bernstein, Jonathan A; Wheeler, Matthew T

    2017-01-01

    Here we describe a patient who presented with a history of congenital diaphragmatic hernia, inguinal hernia, and recurrent umbilical hernia. She also has joint laxity, hypotonia, and dysmorphic features. A unifying diagnosis was not identified based on her clinical phenotype. As part of her evaluation through the Undiagnosed Diseases Network, trio whole-exome sequencing was performed. Pathogenic variants in FBN1 and TRPS1 were identified as causing two distinct autosomal dominant conditions, each with de novo inheritance. Fibrillin 1 (FBN1) mutations are associated with Marfan syndrome and a spectrum of similar phenotypes. TRPS1 mutations are associated with trichorhinophalangeal syndrome types I and III. Features of both conditions are evident in the patient reported here. Discrepant features of the conditions (e.g., stature) and the young age of the patient may have made a clinical diagnosis more difficult in the absence of exome-wide genetic testing.

  5. The Systematic Evaluation of Identifying the Infarct Related Artery Utilizing Cardiac Magnetic Resonance in Patients Presenting with ST-Elevation Myocardial Infarction

    PubMed Central

    Hamo, Carine E.; Klem, Igor; Rao, Sunil V.; Songco, Vincent; Najjar, Samer; Lakatta, Edward G.; Raman, Subha V.; Harrington, Robert A.; Heitner, John F.

    2017-01-01

    Background Identification of the infarct-related artery (IRA) in patients with STEMI using coronary angiography (CA) is often based on the ECG and can be challenging in patients with severe multi-vessel disease. The current study aimed to determine how often percutaneous intervention (PCI) is performed in a coronary artery different from the artery supplying the territory of acute infarction on cardiac magnetic resonance imaging (CMR). Methods We evaluated 113 patients from the Reduction of infarct Expansion and Ventricular remodeling with Erythropoetin After Large myocardial infarction (REVEAL) trial, who underwent CMR within 4±2 days of revascularization. Blinded reviewers interpreted CA to determine the IRA and CMR to determine the location of infarction on a 17-segment model. In patients with multiple infarcts on CMR, acuity was determined with T2-weighted imaging and/or evidence of microvascular obstruction. Results A total of 5 (4%) patients were found to have a mismatch between the IRA identified on CMR and CA. In 4/5 cases, there were multiple infarcts noted on CMR. Thirteen patients (11.5%) had multiple infarcts in separate territories on CMR with 4 patients (3.5%) having multiple acute infarcts and 9 patients (8%) having both acute and chronic infarcts. Conclusions In this select population of patients, the identification of the IRA by CA was incorrect in 4% of patients presenting with STEMI. Four patients with a mismatch had an acute infarction in more than one coronary artery territory on CMR. The role of CMR in patients presenting with STEMI with multi-vessel disease on CA deserves further investigation. PMID:28060863

  6. Accuracy of the Hospital Anxiety and Depression Scale for identifying depression in chronic obstructive pulmonary disease patients.

    PubMed

    Nowak, Christoph; Sievi, Noriane A; Clarenbach, Christian F; Schwarz, Esther Irene; Schlatzer, Christian; Brack, Thomas; Brutsche, Martin; Frey, Martin; Irani, Sarosh; Leuppi, Jörg D; Rüdiger, Jochen; Thurnheer, Robert; Kohler, Malcolm

    2014-01-01

    Psychological morbidity is common in chronic respiratory diseases. The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed. Consecutive COPD patients (GOLD stage I-IV, 40-75 years old) were enrolled in a multicentre, cross-sectional cohort study. Diagnosis of depression was ascertained through clinical records. Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated. Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included. Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]). Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601-0.719), and HADS-Total, AUC 0.681 (95%CI 0.620-0.737), with optimal cut-off scores of >5 and >9, respectively. Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total. Age, comorbidities, sex, and lower airflow limitation predicted depression. The HADS exhibits low diagnostic accuracy for depression in COPD patients. Younger men with comorbidities are at increased risk for depression.

  7. Accuracy of the Hospital Anxiety and Depression Scale for Identifying Depression in Chronic Obstructive Pulmonary Disease Patients

    PubMed Central

    Nowak, Christoph; Sievi, Noriane A.; Clarenbach, Christian F.; Schwarz, Esther Irene; Schlatzer, Christian; Brack, Thomas; Brutsche, Martin; Frey, Martin; Irani, Sarosh; Leuppi, Jörg D.; Rüdiger, Jochen; Thurnheer, Robert; Kohler, Malcolm

    2014-01-01

    Psychological morbidity is common in chronic respiratory diseases. The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed. Consecutive COPD patients (GOLD stage I–IV, 40–75 years old) were enrolled in a multicentre, cross-sectional cohort study. Diagnosis of depression was ascertained through clinical records. Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated. Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included. Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]). Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601–0.719), and HADS-Total, AUC 0.681 (95%CI 0.620–0.737), with optimal cut-off scores of >5 and >9, respectively. Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total. Age, comorbidities, sex, and lower airflow limitation predicted depression. The HADS exhibits low diagnostic accuracy for depression in COPD patients. Younger men with comorbidities are at increased risk for depression. PMID:25548667

  8. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients.

    PubMed

    Tompson, Stuart W J; Ruiz-Perez, Victor L; Blair, Helen J; Barton, Stephanie; Navarro, Victoria; Robson, Joanne L; Wright, Michael J; Goodship, Judith A

    2007-01-01

    Ellis-van Creveld syndrome (EvC) is caused by mutations in EVC and EVC2, genes in a divergent orientation separated by only 2.6 kb. We systematically sought mutations in both genes in a panel of 65 affected individuals to assess the proportion of cases resulting from mutations in each gene. We PCR amplified and sequenced the coding exons of both genes. We investigated mutations that could affect splicing by in vitro splicing assays and cDNA analysis. We have identified EVC mutations in 20 cases (31%); in all of these we have detected the mutation on each allele. We have identified EVC2 mutations in 25 cases (38%); in 22 of these we have isolated a mutation on each allele. The majority of the mutations introduce a premature termination codon. We sequenced the region between the two genes in 10 of the 20 cases in which we had not identified a mutation in either gene, revealing only one SNP that was not a common polymorphism. As we have not identified mutations in either gene in 20 cases (31%) it is possible that there is further genetic heterogeneity.

  9. Why Is Cancer Genetic Counseling Underutilized by Women Identified as at Risk for Hereditary Breast Cancer? Patient Perceptions of Barriers Following a Referral Letter.

    PubMed

    Kne, Alyssa; Zierhut, Heather; Baldinger, Shari; Swenson, Karen K; Mink, Pamela; Veach, Patricia McCarthy; Tsai, Michaela L

    2016-11-08

    Family history information comprises an important tool in identifying and referring patients at risk for hereditary breast and ovarian cancer (HBOC) to cancer genetic counseling. Despite recommendations and support provided by numerous professional organizations, cancer genetic counseling services are underutilized by atrisk patients. This study aimed to: (1) determine the rate of genetic counseling utilization following a referral letter, (2) characterize factors (barriers and supports) which influenced uptake of services, and (3) identify potential strategies for increasing utilization. This study evaluated the uptake of cancer genetic counseling among 603 screening mammography patients identified as having an increased risk for HBOC based on National Comprehensive Cancer Network (NCCN) guidelines. At risk individuals and their primary care providers were mailed a referral letter recommending genetic counseling. Three focus groups (N = 24) were conducted to identify responses to receiving a letter recommending genetic counseling, barriers to seeking genetic counseling, and facilitating factors to utilizing these services. Participant responses were qualitatively analyzed using thematic and cross case analysis. Within one year, 50/603 (8 %) of the identified at-risk women completed a genetic counseling appointment. Participant-perceived barriers which influenced their decision not to seek genetic counseling included lack of relevance and utility, limited knowledge about genetic counseling, concerns about the genetic counseling process, and concerns about cost and insurance coverage. Participant-perceived facilitating factors which would support a decision to seek genetic counseling included greater awareness and education about genetic counseling services when receiving a referral, and improved follow up and guidance from their provider. Findings from this study support the need for patient and primary care provider education, and improved provider-patient

  10. Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

    PubMed

    Ishii, M; Himeno, W; Sawa, M; Iemura, M; Furui, J; Muta, H; Sugahara, Y; Egami, K; Akagi, T; Ishibashi, M; Kato, H

    2002-01-01

    The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

  11. Using individualized predictive disease modeling to identify patients with the potential to benefit from a disease management program for diabetes mellitus.

    PubMed

    Weber, Christian; Neeser, Kurt

    2006-08-01

    Diabetes is an increasing health problem, but efforts to handle this pandemic by disease management programs (DMP) have shown conflicting results. Our hypothesis is that, in addition to a program's content and setting, the choice of the right patients is crucial to a program's efficacy and effectiveness. We used individualized predictive disease modeling (IPDM) on a cohort of 918 patients with type 2 diabetes to identify those patients with the greatest potential to benefit from inclusion in a DMP. A portion of the patients (4.7%) did not have even a theoretical potential for an increase in life expectancy and would therefore be unlikely to benefit from a DMP. Approximately 16.1% had an increase in life expectancy of less than half a year. Stratification of the entire cohort by surrogate parameters like preventable 10-year costs or gain in life expectancy was much more effective than stratification by classical clinical parameters such as high HbA1c level. Preventable costs increased up to 50.6% (or 1,010 per patient (1 = US dollars 1.28), p < 0.01) and life expectancy increased up to 54.8% (or 2.3 years, p < 0.01). IPDM is a valuable strategy to identify those patients with the greatest potential to avoid diabetes-related complications and thus can improve the overall effectiveness and efficacy of DMPs for diabetes mellitus.

  12. HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

    PubMed Central

    Ma, Hui; Yang, Rui-Feng; Li, Xiao-He; Jin, Qian; Wei, Lai

    2016-01-01

    Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN. Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10 kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU. PMID:27625094

  13. SU-E-I-75: Development of New Biological Fingerprints for Patient Recognition to Identify Misfiled Images in a PACS Server

    SciTech Connect

    Shimizu, Y; Yoon, Y; Iwase, K; Yasumatsu, S; Matsunobu, Y; Morishita, J

    2015-06-15

    Purpose: We are trying to develop an image-searching technique to identify misfiled images in a picture archiving and communication system (PACS) server by using five biological fingerprints: the whole lung field, cardiac shadow, superior mediastinum, lung apex, and right lower lung. Each biological fingerprint in a chest radiograph includes distinctive anatomical structures to identify misfiled images. The whole lung field was less effective for evaluating the similarity between two images than the other biological fingerprints. This was mainly due to the variation in the positioning for chest radiographs. The purpose of this study is to develop new biological fingerprints that could reduce influence of differences in the positioning for chest radiography. Methods: Two hundred patients were selected randomly from our database (36,212 patients). These patients had two images each (current and previous images). Current images were used as the misfiled images in this study. A circumscribed rectangular area of the lung and the upper half of the rectangle were selected automatically as new biological fingerprints. These biological fingerprints were matched to all previous images in the database. The degrees of similarity between the two images were calculated for the same and different patients. The usefulness of new the biological fingerprints for automated patient recognition was examined in terms of receiver operating characteristic (ROC) analysis. Results: Area under the ROC curves (AUCs) for the circumscribed rectangle of the lung, upper half of the rectangle, and whole lung field were 0.980, 0.994, and 0.950, respectively. The new biological fingerprints showed better performance in identifying the patients correctly than the whole lung field. Conclusion: We have developed new biological fingerprints: circumscribed rectangle of the lung and upper half of the rectangle. These new biological fingerprints would be useful for automated patient identification system

  14. Genome-Wide Association Study Identifies That the ABO Blood Group System Influences Interleukin-10 Levels and the Risk of Clinical Events in Patients with Acute Coronary Syndrome

    PubMed Central

    Johansson, Åsa; Alfredsson, Jenny; Eriksson, Niclas; Wallentin, Lars; Siegbahn, Agneta

    2015-01-01

    Introduction Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients. Method We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers. Results Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 × 10−10) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 × 10−13), and soluble tissue factor (sTF, P = 8.6 × 10−4) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 × 10−15 and P = 1.0 × 10−5 respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24–1.29, P = 0.029–0.00067). Conclusion Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease. PMID:26600159

  15. Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records

    PubMed Central

    Restrepo, Nicole A.; Butkiewicz, Mariusz; McGrath, Josephine A.; Crawford, Dana C.

    2016-01-01

    Autoimmune diseases represent a significant medical burden affecting up to 5–8% of the U.S. population. While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, and a single disease approach. Here we performed a targeted genetic association study for cases of multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease (CD) to assess which common genetic variants contribute individually and pleiotropically to disease risk. Joint modeling and pathway analysis combining the three phenotypes were performed to identify common underlying mechanisms of risk of autoimmune conditions. European American cases of MS, RA, and CD, (n = 119, 53, and 129, respectively) and 1924 controls were identified using de-identified electronic health records (EHRs) through a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) billing codes, Current Procedural Terminology (CPT) codes, medication lists, and text matching. As expected, hallmark SNPs in MS, such as DQA1 rs9271366 (OR = 1.91; p = 0.008), replicated in the present study. Both MS and CD were associated with TIMMDC1 rs2293370 (OR = 0.27, p = 0.01; OR = 0.25, p = 0.02; respectively). Additionally, PDE2A rs3781913 was significantly associated with both CD and RA (OR = 0.46, p = 0.02; OR = 0.32, p = 0.02; respectively). Joint modeling and pathway analysis identified variants within the KEGG NOD-like receptor signaling pathway and Shigellosis pathway as being correlated with the combined autoimmune phenotype. Our study replicated previously-reported genetic associations for MS and CD in a population derived from de-identified EHRs. We found evidence to support a shared genetic etiology between CD/MS and CD/RA outside of the major histocompatibility complex region and identified KEGG pathways indicative of a bacterial pathogenesis risk for autoimmunity in a joint model. Future work to

  16. Accurate Evaluation of Quantum Integrals

    NASA Technical Reports Server (NTRS)

    Galant, D. C.; Goorvitch, D.; Witteborn, Fred C. (Technical Monitor)

    1995-01-01

    Combining an appropriate finite difference method with Richardson's extrapolation results in a simple, highly accurate numerical method for solving a Schrodinger's equation. Important results are that error estimates are provided, and that one can extrapolate expectation values rather than the wavefunctions to obtain highly accurate expectation values. We discuss the eigenvalues, the error growth in repeated Richardson's extrapolation, and show that the expectation values calculated on a crude mesh can be extrapolated to obtain expectation values of high accuracy.

  17. How to identify existing literature on patients' knowledge, views, and values: the development of a validated search filter

    PubMed Central

    Wessels, Monique; Hielkema, Lian; van der Weijden, Trudy

    2016-01-01

    Objective The research sought to establish validated search filters for retrieval of studies on patients' knowledge and values. Setting Two nonprofit organizations in the Netherlands were studied for guideline development. Methods An existing filter was adapted to three bibliographic interfaces. After defining the scope, a reference database was built for the development of the new filters. The performance of the new filters was validated in different disease categories. Results Sensitivity, specificity, precision, negative predictive value, and accuracy were (%): 90.5/98/77/99.2/97 (MEDLINE-Ovid), 90.1/98.8/79.3/99.5/98.3 (PubMed), and 93.1/98.4/81.8/99.6/98.7 (Embase). Conclusions The filters provide pragmatic tools for searching for patients' issues. Further optimization and validation is recommended. PMID:27822157

  18. Three-dimensional quantitative imaging of telomeres in buccal cells identifies mild, moderate, and severe Alzheimer's disease patients.

    PubMed

    Mathur, Shubha; Glogowska, Aleksandra; McAvoy, Elizabeth; Righolt, Christiaan; Rutherford, Jaclyn; Willing, Cornelia; Banik, Upama; Ruthirakuhan, Myuri; Mai, Sabine; Garcia, Angeles

    2014-01-01

    Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).

  19. Identifying Engineering, Clinical and Patient's Metrics for Evaluating and Quantifying Performance of Brain-Machine Interface (BMI) Systems.

    PubMed

    Contreras-Vidal, Jose L

    2014-10-05

    Brain-machine interface (BMI) devices have unparalleled potential to restore functional movement capabilities to stroke, paralyzed and amputee patients. Although BMI systems have achieved success in a handful of investigative studies, translation of closed-loop neuroprosthetic devices from the laboratory to the market is challenged by gaps in the scientific data regarding long-term device reliability and safety, uncertainty in the regulatory, market and reimbursement pathways, lack of metrics for evaluating and quantifying performance in BMI systems, as well as patient-acceptance challenges that impede their fast and effective translation to the end user. This review focuses on the identification of engineering, clinical and user's BMI metrics for new and existing BMI applications.

  20. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    PubMed Central

    Wang, Yingchun; Khan, Salman; Li, Wei; Zhang, Ping L.

    2015-01-01

    Sickle cell nephropathy (SCN) is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI). Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+) was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA) and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2) rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associ