Science.gov

Sample records for accurately identify patients

  1. Optical coherence tomography accurately identifies patients with penile (pre) malignant lesions: A single center prospective study

    PubMed Central

    Wessels, Ronni; De Bruin, Daniel M.; Faber, Dirk J.; Horenblas, Simon; van Rhijn, Bas W. G.; Vincent, Andrew D.; van Beurden, Marc; van Leeuwen, Ton G.; Ruers, Theo J. M.

    2015-01-01

    Introduction: Currently, (multiple) biopsies are taken to obtain histopathological diagnosis of suspicious lesions of the penile skin. Optical coherence tomography (OCT) provides noninvasive in vivo images from which epidermal layer thickness and attenuation coefficient (μoct) can be quantified. We hypothesize that qualitative (image assessment) and quantitative (epidermal layer thickness and attenuation coefficient, μoct) analysis of penile skin with OCT is possible and may differentiate benign penile tissue from (pre) malignant penile tissue. Materials and Methods: Optical coherence tomography-imaging was performed prior to punch biopsy in 18 consecutive patients with a suspicious lesion at the outpatient clinic of the NKI-AVL. Qualitative analysis consisted of visual assessment of clear layers and a visible lower border of the lesions, quantitative analysis comprised of determination of the epidermal layer thickness and μoct. Results were grouped according to histopathology reports. Results: Qualitative analysis showed a statistically significant difference (P = 0.047) between benign and (pre) malignant lesions. Quantitative analysis showed that epidermal layer thickness and attenuation coefficient was significantly different between benign and (pre) malignant tissue, respectively, P = 0.001 and P < 0.001. Conclusion: In this preliminary study, qualitative and quantitative analysis of OCT-images of suspicious penile lesions shows differences between benign lesions and (pre) malignant lesions. These results encourage further research in a larger study population. PMID:26692665

  2. Administrative Codes Combined with Medical Records-based Criteria Accurately Identified Bacterial Infections among Rheumatoid Arthritis Patients

    PubMed Central

    Patkar, Nivedita M.; Curtis, Jeffrey R.; Teng, Gim Gee; Allison, Jeroan J.; Saag, Michael; Martin, Carolyn; Saag, Kenneth G.

    2009-01-01

    Objective To evaluate diagnostic properties of International Classification of Diseases, Version 9 (ICD-9) diagnosis codes and infection criteria to identify bacterial infections among rheumatoid arthritis (RA) patients. Study Design and Setting We performed a cross- sectional study of RA patients with and without ICD-9 codes for bacterial infections. Sixteen bacterial infection criteria were developed. Diagnostic properties of comprehensive and restrictive sets of ICD-9 codes and the infection criteria were tested against an adjudicated review of medical records. Results Records on 162 RA patients with and 50 without purported bacterial infections were reviewed. Positive (PPV) and negative predictive values (NPVs) of ICD-9 codes ranged from 54% – 85% and 84% – 100%, respectively. PPVs of the medical records-based criteria were: 84% and 89% for “definite” and “definite or empirically treated” infections, respectively. PPV of infection criteria increased by 50% as disease prevalence increased using ICD-9 codes to enhance infection likelihood. Conclusion ICD-9 codes alone may misclassify bacterial infections in hospitalized RA patients. Misclassification varies with the specificity of the codes used and strength of evidence required to confirm infections. Combining ICD-9 codes with infection criteria identified infections with greatest accuracy. Novel infection criteria may limit the requirement to review medical records. PMID:18834713

  3. Postmortem CT is more accurate than clinical diagnosis for identifying the immediate cause of death in hospitalized patients: a prospective autopsy-based study.

    PubMed

    Inai, Kunihiro; Noriki, Sakon; Kinoshita, Kazuyuki; Sakai, Toyohiko; Kimura, Hirohiko; Nishijima, Akihiko; Iwasaki, Hiromichi; Naiki, Hironobu

    2016-07-01

    Despite 75 to 90 % physician accuracy in determining the underlying cause of death, precision of determination of the immediate cause of death is approximately 40 %. In contrast, two thirds of immediate causes of death in hospitalized patients are correctly diagnosed by postmortem computed tomography (CT). Postmortem CT might provide an alternative approach to verifying the immediate cause of death. To evaluate the effectiveness of postmortem CT as an alternative method to determine the immediate cause of death in hospitalized patients, an autopsy-based prospective study was performed. Of 563 deaths from September 2011 to August 2013, 50 consecutive cadavers undergoing hospital autopsies with consent for additional postmortem CT at the University of Fukui were enrolled. The accuracy of determination of the immediate cause of death by postmortem CT was evaluated in these patients. Diagnostic discrepancy was also compared between radiologists and attending physicians. The immediate cause of death was correctly diagnosed in 37 of 50 subjects using postmortem CT (74 %), concerning 29 cases of respiratory failure, 4 of hemorrhage, 3 of liver failure and 1 of septic shock. Six cases of organ failure involving 13 patients were not identified as the cause of death by postmortem CT. Regarding the immediate cause of death, accuracy of clinical diagnosis was significantly lower than that of postmortem CT (46 vs 74 %, P < 0.01). Postmortem CT may be more useful than clinical diagnosis for identifying the immediate cause of death in hospitalized patients not undergoing autopsy. PMID:27085336

  4. 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…

  5. Are general practitioners able to accurately diagnose dementia and identify Alzheimer's disease? A comparison with an outpatient memory clinic.

    PubMed Central

    van Hout, H; Vernooij-Dassen, M; Poels, P; Hoefnagels, W; Grol, R

    2000-01-01

    Since the introduction of agents for the treatment of Alzheimer's disease, and in order to increase understanding of a patient's changed behaviour, it has become particularly important that dementia is both diagnosed at an early stage and differentiated into its subtypes. This study aims to ascertain whether GPs were able to diagnose dementia and identify the type of dementia accurately and confidently. GPs were well able to assess the firmness of their own dementia diagnoses, which supposes that they are able to make appropriate selection for referral. Diagnostic support from a specialised team can particularly contribute to identifying the type of dementia. PMID:10897518

  6. 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

  7. RNA-Seq accurately identifies cancer biomarker signatures to distinguish tissue of origin.

    PubMed

    Wei, Iris H; Shi, Yang; Jiang, Hui; Kumar-Sinha, Chandan; Chinnaiyan, Arul M

    2014-11-01

    Metastatic cancer of unknown primary (CUP) accounts for up to 5% of all new cancer cases, with a 5-year survival rate of only 10%. Accurate identification of tissue of origin would allow for directed, personalized therapies to improve clinical outcomes. Our objective was to use transcriptome sequencing (RNA-Seq) to identify lineage-specific biomarker signatures for the cancer types that most commonly metastasize as CUP (colorectum, kidney, liver, lung, ovary, pancreas, prostate, and stomach). RNA-Seq data of 17,471 transcripts from a total of 3,244 cancer samples across 26 different tissue types were compiled from in-house sequencing data and publically available International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Robust cancer biomarker signatures were extracted using a 10-fold cross-validation method of log transformation, quantile normalization, transcript ranking by area under the receiver operating characteristic curve, and stepwise logistic regression. The entire algorithm was then repeated with a new set of randomly generated training and test sets, yielding highly concordant biomarker signatures. External validation of the cancer-specific signatures yielded high sensitivity (92.0% ± 3.15%; mean ± standard deviation) and specificity (97.7% ± 2.99%) for each cancer biomarker signature. The overall performance of this RNA-Seq biomarker-generating algorithm yielded an accuracy of 90.5%. In conclusion, we demonstrate a computational model for producing highly sensitive and specific cancer biomarker signatures from RNA-Seq data, generating signatures for the top eight cancer types responsible for CUP to accurately identify tumor origin. PMID:25425966

  8. 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

  9. Pseudonymization of patient identifiers for translational research

    PubMed Central

    2013-01-01

    Background The usage of patient data for research poses risks concerning the patients’ privacy and informational self-determination. Next-generation-sequencing technologies and various other methods gain data from biospecimen, both for translational research and personalized medicine. If these biospecimen are anonymized, individual research results from genomic research, which should be offered to patients in a clinically relevant timeframe, cannot be associated back to the individual. This raises an ethical concern and challenges the legitimacy of anonymized patient samples. In this paper we present a new approach which supports both data privacy and the possibility to give feedback to patients about their individual research results. Methods We examined previously published privacy concepts regarding a streamlined de-pseudonymization process and a patient-based pseudonym as applicable to research with genomic data and warehousing approaches. All concepts identified in the literature review were compared to each other and analyzed for their applicability to translational research projects. We evaluated how these concepts cope with challenges implicated by personalized medicine. Therefore, both person-centricity issues and a separation of pseudonymization and de-pseudonymization stood out as a central theme in our examination. This motivated us to enhance an existing pseudonymization method regarding a separation of duties. Results The existing concepts rely on external trusted third parties, making de-pseudonymization a multistage process involving additional interpersonal communication, which might cause critical delays in patient care. Therefore we propose an enhanced method with an asymmetric encryption scheme separating the duties of pseudonymization and de-pseudonymization. The pseudonymization service provider is unable to conclude the patient identifier from the pseudonym, but assigns this ability to an authorized third party (ombudsman) instead. To solve

  10. DomHR: Accurately Identifying Domain Boundaries in Proteins Using a Hinge Region Strategy

    PubMed Central

    Zhang, Xiao-yan; Lu, Long-jian; Song, Qi; Yang, Qian-qian; Li, Da-peng; Sun, Jiang-ming; Li, Tong-hua; Cong, Pei-sheng

    2013-01-01

    Motivation The precise prediction of protein domains, which are the structural, functional and evolutionary units of proteins, has been a research focus in recent years. Although many methods have been presented for predicting protein domains and boundaries, the accuracy of predictions could be improved. Results In this study we present a novel approach, DomHR, which is an accurate predictor of protein domain boundaries based on a creative hinge region strategy. A hinge region was defined as a segment of amino acids that covers part of a domain region and a boundary region. We developed a strategy to construct profiles of domain-hinge-boundary (DHB) features generated by sequence-domain/hinge/boundary alignment against a database of known domain structures. The DHB features had three elements: normalized domain, hinge, and boundary probabilities. The DHB features were used as input to identify domain boundaries in a sequence. DomHR used a nonredundant dataset as the training set, the DHB and predicted shape string as features, and a conditional random field as the classification algorithm. In predicted hinge regions, a residue was determined to be a domain or a boundary according to a decision threshold. After decision thresholds were optimized, DomHR was evaluated by cross-validation, large-scale prediction, independent test and CASP (Critical Assessment of Techniques for Protein Structure Prediction) tests. All results confirmed that DomHR outperformed other well-established, publicly available domain boundary predictors for prediction accuracy. Availability The DomHR is available at http://cal.tongji.edu.cn/domain/. PMID:23593247

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

    PubMed Central

    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

  12. 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

  13. 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…

  14. 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. PMID:27396802

  15. 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

  16. 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...

  17. Do Ecological Niche Models Accurately Identify Climatic Determinants of Species Ranges?

    PubMed

    Searcy, Christopher A; Shaffer, H Bradley

    2016-04-01

    Defining species' niches is central to understanding their distributions and is thus fundamental to basic ecology and climate change projections. Ecological niche models (ENMs) are a key component of making accurate projections and include descriptions of the niche in terms of both response curves and rankings of variable importance. In this study, we evaluate Maxent's ranking of environmental variables based on their importance in delimiting species' range boundaries by asking whether these same variables also govern annual recruitment based on long-term demographic studies. We found that Maxent-based assessments of variable importance in setting range boundaries in the California tiger salamander (Ambystoma californiense; CTS) correlate very well with how important those variables are in governing ongoing recruitment of CTS at the population level. This strong correlation suggests that Maxent's ranking of variable importance captures biologically realistic assessments of factors governing population persistence. However, this result holds only when Maxent models are built using best-practice procedures and variables are ranked based on permutation importance. Our study highlights the need for building high-quality niche models and provides encouraging evidence that when such models are built, they can reflect important aspects of a species' ecology. PMID:27028071

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

    PubMed

    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

    2016-05-01

    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

  19. 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

  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. Using complete genome comparisons to identify sequences whose presence accurately predicts clinically important phenotypes.

    PubMed

    Hall, Barry G; Cardenas, Heliodoro; Barlow, Miriam

    2013-01-01

    In clinical settings it is often important to know not just the identity of a microorganism, but also the danger posed by that particular strain. For instance, Escherichia coli can range from being a harmless commensal to being a very dangerous enterohemorrhagic (EHEC) strain. Determining pathogenic phenotypes can be both time consuming and expensive. Here we propose a simple, rapid, and inexpensive method of predicting pathogenic phenotypes on the basis of the presence or absence of short homologous DNA segments in an isolate. Our method compares completely sequenced genomes without the necessity of genome alignments in order to identify the presence or absence of the segments to produce an automatic alignment of the binary string that describes each genome. Analysis of the segment alignment allows identification of those segments whose presence strongly predicts a phenotype. Clinical application of the method requires nothing more that PCR amplification of each of the set of predictive segments. Here we apply the method to identifying EHEC strains of E. coli and to distinguishing E. coli from Shigella. We show in silico that with as few as 8 predictive sequences, if even three of those predictive sequences are amplified the probability of being EHEC or Shigella is >0.99. The method is thus very robust to the occasional amplification failure for spurious reasons. Experimentally, we apply the method to screening a set of 98 isolates to distinguishing E. coli from Shigella, and EHEC from non-EHEC E. coli strains and show that all isolates are correctly identified. PMID:23935901

  2. 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.

  3. 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

  4. Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma

    PubMed Central

    Andresen, Kim; Boberg, Kirsten Muri; Vedeld, Hege Marie; Honne, Hilde; Jebsen, Peter; Hektoen, Merete; Wadsworth, Christopher A.; Clausen, Ole Petter; Lundin, Knut E.A.; Paulsen, Vemund; Foss, Aksel; Mathisen, Øystein; Aabakken, Lars; Schrumpf, Erik; Lothe, Ragnhild A.

    2015-01-01

    Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation‐specific polymerase chain reaction. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 nonmalignant primary sclerosing cholangitis controls), and the methylation status of the four best performing markers was validated (34 CCAs and 34 primary sclerosing cholangitis controls). Receiver operating characteristic curve analyses were used to evaluate the performance of individual biomarkers and the combination of biomarkers. The 13 candidate genes displayed a methylation frequency of 26%‐82% in tissue samples. The four best‐performing genes (CDO1, CNRIP1, SEPT9, and VIM) displayed individual methylation frequencies of 45%‐77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four‐gene biomarker panel achieved a sensitivity of 85% and a specificity of 98%, with an area under the receiver operating characteristic curve of 0.944. Conclusion: We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology, and suggest that the biomarker panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among primary sclerosing cholangitis patients. (Hepatology 2015;61:1651–1659) PMID:25644509

  5. Identity cards help patients identify their doctors.

    PubMed

    Zucco, Liana; Desmond, Gabrielle; Carpenter, Bernadette

    2014-01-01

    Patients admitted to hospital are immediately overloaded with information from staff in A&E, to subsequent acute medical and inpatient wards. Essential details are conveyed to patients at each step, including diagnosis, management and identification of various team members involved in their care. An initial audit within our South London hospital revealed only one third of patients admitted onto a single medical ward could recall the name of a single member of their treating team, and less than 10% retained that information over 5 days. Identification (ID) cards were devised to facilitate clear transfer of information detailing the patient's treating team. These ID cards were piloted through a series of PDSA cycles on one inpatient medical ward following a consultant led ward round. Post intervention, 67% managed to recall a single member of the treating team, with 67% retaining this information 5 days later, a dramatic improvement. ID cards were then trialed on one surgical ward, demonstrating equally impressive results with over 87% of patients recalling their named consultant following ID card implementation, up from 54% initially. Similar trends were demonstrated for recalling other treating team members. This simple measure improved patients ability to recall and retain names of a least a single member of their treating team, encouraged communication between patients and medical team and ultimately improved patient satisfaction and quality of care. ID cards were quick and easy to implement and have been approved by the hospital patient safety committee to implement throughout the Trust. PMID:26734234

  6. Are housestaff identifying malnourished hospitalized medicine patients?

    PubMed

    Mitchell, Michael A; Duerksen, Donald R; Rahman, Adam

    2014-10-01

    Clinical nutrition and nutritional assessment are often a neglected component of medical school curriculums despite the high prevalence of malnutrition in hospitalized patients. This study found that medical housestaff performed nutritional assessments in only 4% of admitted patients despite a high rate of malnutrition (57%). Survey results show housestaff lack knowledge in the area of malnutrition. Medical schools and training programs must place greater emphasis of providing qualified physician nutrition specialists to implement effective nutrition instruction. PMID:25061765

  7. Geometric complexity identifies platelet activation in familial hypercholesterolemic patients.

    PubMed

    Bianciardi, Giorgio; Aglianò, Margherita; Volpi, Nila; Stefanutti, Claudia

    2015-06-01

    Familial hypercholesterolemia (FH), a genetic disease, is associated with a severe incidence of athero-thrombotic events, related, also, to platelet hyperreactivity. A plethora of methods have been proposed to identify those activated circulating platelets, none of these has proved really effective. We need efficient methods to identify the circulating platelet status in order to follow the patients after therapeutic procedures. We propose the use of computerized fractal analysis for an objective characterization of the complexity of circulating platelet shapes observed by means of transmission electron microscopy in order to characterize the in vivo hyperactivated platelets of familial hypercholesterolemic patients, distinguishing them from the in vivo resting platelets of healthy individuals. Platelet boundaries were extracted by means of automatically image analysis. Geometric complexity (fractal dimension, D) by box counting was automatically calculated. The platelet boundary observed by electron microscopy is fractal, the shape of the circulating platelets is more complex in FH (n = 6) than healthy subjects (n = 5, P < 0.01), with 100% correct classification in selected individuals. In vitro activated platelets from healthy subjects show an analogous increase of D. The observed high D in the platelet boundary in FH originates from the in vivo platelet activation. Computerized fractal analysis of platelet shape observed by transmission electron microscopy can provide accurate, quantitative data to study platelet activation in familial hypercholesterolemia and after administration of drugs or other therapeutic procedures. PMID:25877374

  8. Accurate multimodal probabilistic prediction of conversion to Alzheimer's disease in patients with mild cognitive impairment☆

    PubMed Central

    Young, Jonathan; Modat, Marc; Cardoso, Manuel J.; Mendelson, Alex; Cash, Dave; Ourselin, Sebastien

    2013-01-01

    Accurately identifying the patients that have mild cognitive impairment (MCI) who will go on to develop Alzheimer's disease (AD) will become essential as new treatments will require identification of AD patients at earlier stages in the disease process. Most previous work in this area has centred around the same automated techniques used to diagnose AD patients from healthy controls, by coupling high dimensional brain image data or other relevant biomarker data to modern machine learning techniques. Such studies can now distinguish between AD patients and controls as accurately as an experienced clinician. Models trained on patients with AD and control subjects can also distinguish between MCI patients that will convert to AD within a given timeframe (MCI-c) and those that remain stable (MCI-s), although differences between these groups are smaller and thus, the corresponding accuracy is lower. The most common type of classifier used in these studies is the support vector machine, which gives categorical class decisions. In this paper, we introduce Gaussian process (GP) classification to the problem. This fully Bayesian method produces naturally probabilistic predictions, which we show correlate well with the actual chances of converting to AD within 3 years in a population of 96 MCI-s and 47 MCI-c subjects. Furthermore, we show that GPs can integrate multimodal data (in this study volumetric MRI, FDG-PET, cerebrospinal fluid, and APOE genotype with the classification process through the use of a mixed kernel). The GP approach aids combination of different data sources by learning parameters automatically from training data via type-II maximum likelihood, which we compare to a more conventional method based on cross validation and an SVM classifier. When the resulting probabilities from the GP are dichotomised to produce a binary classification, the results for predicting MCI conversion based on the combination of all three types of data show a balanced accuracy

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. New Cardiovascular Risk Factors and Their Use for an Accurate Cardiovascular Risk Assessment in Hypertensive Patients

    PubMed Central

    TAUTU, Oana-Florentina; DARABONT, Roxana; ONCIUL, Sebastian; DEACONU, Alexandru; COMANESCU, Ioana; ANDREI, Radu Dan; DRAGOESCU, Bogdan; CINTEZA, Mircea; DOROBANTU, Maria

    2014-01-01

    Objectives: To analyze the predictive value of new cardiovascular (CV) risk factors for CV risk assessment in the adult Romanian hypertensive (HT) population. Methods: Hypertensive adults aged between 40-65 years of age, identified in national representative SEPHAR II survey were evaluated by anthropometric, BP and arterial stiffness measurements: aortic pulse wave velocity (PWVao), aortic augmentation index (AIXao), revers time (RT) and central systolic blood pressure (SBPao), 12 lead ECGs and laboratory workup. Values above the 4th quartile of mean SBP' standard deviation (s.d.) defined increased BP variability. Log(TG/HDL-cholesterol) defined atherogenic index of plasma (AIP). Serum uric acid levels above 5.70 mg/dl for women and 7.0 mg/dl for males defined hyperuricemia (HUA). CV risk was assessed based on SCORE chart for high CV risk countries. Binary logistic regression using a stepwise likelihood ratio method (adjustments for major confounders and colliniarity analysis) was used in order to validate predictors of high and very high CV risk class. Results: The mean SBP value of the study group was 148.46±19.61 mmHg. Over forty percent of hypertensives had a high and very high CV risk. Predictors of high/very high CV risk category validated by regression analysis were: increased visit-to-visit BP variability (OR: 2.49; 95%CI: 1.67-3.73), PWVao (OR: 1.12; 95%CI: 1.02-1.22), RT (OR: 0.95; 95% CI: 0.93-0.98), SBPao (OR: 1.01; 95%CI: 1.01-1.03) and AIP (OR: 7.08; 95%CI: 3.91-12.82). Conclusion: The results of our study suggests that the new CV risk factors such as increased BP variability, arterial stiffness indices and AIP are useful tools for a more accurate identification of hypertensives patients at high and very high CV risk. PMID:25705267

  15. Are Patient-Specific Joint and Inertial Parameters Necessary for Accurate Inverse Dynamics Analyses of Gait?

    PubMed Central

    Reinbolt, Jeffrey A.; Haftka, Raphael T.; Chmielewski, Terese L.; Fregly, Benjamin J.

    2013-01-01

    Variations in joint parameter values (axis positions and orientations in body segments) and inertial parameter values (segment masses, mass centers, and moments of inertia) as well as kinematic noise alter the results of inverse dynamics analyses of gait. Three-dimensional linkage models with joint constraints have been proposed as one way to minimize the effects of noisy kinematic data. Such models can also be used to perform gait optimizations to predict post-treatment function given pre-treatment gait data. This study evaluates whether accurate patient-specific joint and inertial parameter values are needed in three-dimensional linkage models to produce accurate inverse dynamics results for gait. The study was performed in two stages. First, we used optimization analyses to evaluate whether patient-specific joint and inertial parameter values can be calibrated accurately from noisy kinematic data, and second, we used Monte Carlo analyses to evaluate how errors in joint and inertial parameter values affect inverse dynamics calculations. Both stages were performed using a dynamic, 27 degree-of-freedom, full-body linkage model and synthetic (i.e., computer generated) gait data corresponding to a nominal experimental gait motion. In general, joint but not inertial parameter values could be found accurately from noisy kinematic data. Root-mean-square (RMS) errors were 3° and 4 mm for joint parameter values and 1 kg, 22 mm, and 74,500 kg*mm2 for inertial parameter values. Furthermore, errors in joint but not inertial parameter values had a significant effect on calculated lower-extremity inverse dynamics joint torques. The worst RMS torque error averaged 4% bodyweight*height (BW*H) due to joint parameter variations but less than 0.25% BW*H due to inertial parameter variations. These results suggest that inverse dynamics analyses of gait utilizing linkage models with joint constraints should calibrate the model’s joint parameter values to obtain accurate joint

  16. How Accurate Are Blood (or Breath) Tests for Identifying Self-Reported Heavy Drinking Among People with Alcohol Dependence?

    PubMed Central

    Bertholet, Nicolas; Winter, Michael R.; Cheng, Debbie M.; Samet, Jeffrey H.; Saitz, Richard

    2014-01-01

    Aims Managing patients with alcohol dependence includes assessment for heavy drinking, typically by asking patients. Some recommend biomarkers to detect heavy drinking but evidence of accuracy is limited. Methods Among people with dependence, we assessed the performance of disialo-carbohydrate-deficient transferrin (%dCDT, ≥1.7%), gamma-glutamyltransferase (GGT, ≥66 U/l), either %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported heavy drinking levels: any heavy drinking (≥4 drinks/day or >7 drinks/week for women, ≥5 drinks/day or >14 drinks/week for men), recurrent (≥5 drinks/day on ≥5 days) and persistent heavy drinking (≥5 drinks/day on ≥7 consecutive days). Subjects (n = 402) with dependence and current heavy drinking were referred to primary care and assessed 6 months later with biomarkers and validated self-reported calendar method assessment of past 30-day alcohol use. Results The self-reported prevalence of any, recurrent and persistent heavy drinking was 54, 34 and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self-reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%, respectively. %dCDT had higher sensitivity than GGT and breath test for each alcohol use level but was not adequately sensitive to detect heavy drinking (missing 34–59% of the cases). Either %dCDT or GGT positive improved sensitivity but not to satisfactory levels, and specificity decreased. Neither a breath test nor GGT was sufficiently sensitive (both tests missed 70–80% of cases). Conclusions Although biomarkers may provide some useful information, their sensitivity is low the incremental value over self-report in clinical settings is questionable. PMID:24740846

  17. Detection and accurate identification of new or emerging bacteria in cystic fibrosis patients.

    PubMed

    Bittar, F; Rolain, J-M

    2010-07-01

    Respiratory infections remain a major threat to cystic fibrosis (CF) patients. The detection and correct identification of the bacteria implicated in these infections is critical for the therapeutic management of patients. The traditional methods of culture and phenotypic identification of bacteria lack both sensitivity and specificity because many bacteria can be missed and/or misidentified. Molecular analyses have recently emerged as useful means to resolve these problems, including molecular methods for accurate identification or detection of bacteria and molecular methods for evaluation of microbial diversity. These recent molecular technologies have increased the list of new and/or emerging pathogens and epidemic strains associated with CF patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of intact cells has also emerged recently as a powerful and rapid method for the routine identification of bacteria in clinical microbiology laboratories and will certainly represent the method of choice also for the routine identification of bacteria in the context of CF. Finally, recent data derived from molecular culture-independent analyses indicate the presence of a previously underestimated, complex microbial community in sputa from CF patients. Interestingly, full genome sequencing of some bacteria frequently recovered from CF patients has highlighted the fact that the lungs of CF patients are hotspots for lateral gene transfer and the adaptation of these ecosystems to a specific chronic condition. PMID:20880410

  18. Identity Management Systems in Healthcare: The Issue of Patient Identifiers

    NASA Astrophysics Data System (ADS)

    Soenens, Els

    According to a recent recommendation of the European Commission, now is the time for Europe to enhance interoperability in eHealth. Although interoperability of patient identifiers seems promising for matters of patient mobility, patient empowerment and effective access to care, we see that today there is indeed a considerable lack of interoperability in the field of patient identification. Looking from a socio-technical rather than a merely technical point of view, one can understand the fact that the development and implementation of an identity management system in a specific healthcare context is influenced by particular social practices, affected by socio-economical history and the political climate and regulated by specific data protection legislations. Consequently, the process of making patient identification in Europe more interoperable is a development beyond semantic and syntactic levels. In this paper, we gives some examples of today’s patient identifier systems in Europe, discuss the issue of interoperability of (unique) patient identifiers from a socio-technical point of view and try not to ignore the ‘privacy side’ of the story.

  19. Identifying the needs of brain tumor patients and their caregivers.

    PubMed

    Parvataneni, Rupa; Polley, Mei-Yin; Freeman, Teresa; Lamborn, Kathleen; Prados, Michael; Butowski, Nicholas; Liu, Raymond; Clarke, Jennifer; Page, Margaretta; Rabbitt, Jane; Fedoroff, Anne; Clow, Emelia; Hsieh, Emily; Kivett, Valerie; Deboer, Rebecca; Chang, Susan

    2011-09-01

    The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers' questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were "very important" but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients' lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value < 0.001). This study provides insights into areas to improve services for brain tumor patients and their caregivers. The caregivers' highest amount of burden is placed on their emotional needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients' treatment process. PMID:21311950

  20. Identifying patients with asthma in primary care electronic medical record systems

    PubMed Central

    Xi, Nancy; Wallace, Rebecca; Agarwal, Gina; Chan, David; Gershon, Andrea; Gupta, Samir

    2015-01-01

    Objective To develop and test a variety of electronic medical record (EMR) search algorithms to allow clinicians to accurately identify their patients with asthma in order to enable improved care. Design A retrospective chart analysis identified 5 relevant unique EMR information fields (electronic disease registry, cumulative patient profile, billing diagnostic code, medications, and chart notes); asthma-related search terms were designated for each field. The accuracy of each term was tested for its ability to identify the asthma patients among all patients whose charts were reviewed. Increasingly sophisticated search algorithms were then designed and evaluated by serially combining individual searches with Boolean operators. Setting Two large academic primary care clinics in Hamilton, Ont. Participants Charts for 600 randomly selected patients aged 16 years and older identified in an initial EMR search as likely having asthma (n = 150), chronic obstructive pulmonary disease (n = 150), other respiratory conditions (n = 150), or nonrespiratory conditions (n = 150) were reviewed until 100 patients per category were identified (or until all available names were exhausted). A total of 398 charts were reviewed in full and included. Main outcome measures Sensitivity and specificity of each search for asthma diagnosis (against the reference standard of a physician chart review–based diagnosis). Results Two physicians reviewed the charts identified in the initial EMR search using a standardized data collection form and ascribed the following diagnoses in 398 patients: 112 (28.1%) had asthma, 81 (20.4%) had chronic obstructive pulmonary disease, 104 (26.1%) had other respiratory conditions, and 101 (25.4%) had nonrespiratory conditions. Concordance between reviewers in chart abstraction diagnosis was high (κ = 0.89, 95% CI 0.80 to 0.97). Overall, the algorithm searching for patients who had asthma in their cumulative patient profiles or for whom an asthma billing code

  1. Priority patient safety issues identified by perioperative nurses.

    PubMed

    Steelman, Victoria M; Graling, Paula R; Perkhounkova, Yelena

    2013-04-01

    Much of the work done by perioperative nurses focuses on patient safety. Perioperative nurses are aware that unreported near misses occur every day, and they use that knowledge to prioritize activities to protect the patient. The purpose of this study was to identify the highest priority patient safety issues reported by perioperative RNs. We sent a link to an anonymous electronic survey to all AORN members who had e-mail addresses in AORN's member database. The survey asked respondents to identify top perioperative patient safety issues. We received 3,137 usable responses and identified the 10 highest priority safety issues, including wrong site/procedure/patient surgery, retained surgical items, medication errors, failures in instrument reprocessing, pressure injuries, specimen management errors, surgical fires, perioperative hypothermia, burns from energy devices, and difficult intubation/airway emergencies. Differences were found among practice settings. The information from this study can be used to inform the development of educational programs and the allocation of resources to enhance safe perioperative patient care. PMID:23531307

  2. 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. PMID:18214724

  3. Accurate genetic diagnosis of Finnish pulmonary arterial hypertension patients using oligonucleotide-selective sequencing

    PubMed Central

    Vattulainen, Sanna; Aho, Joonas; Salmenperä, Pertteli; Bruce, Siina; Tallila, Jonna; Gentile, Massimiliano; Sankelo, Marja; Laitinen, Tarja; Koskenvuo, Juha W; Alastalo, Tero-Pekka; Myllykangas, Samuel

    2015-01-01

    The genetic basis of pulmonary arterial hypertension (PAH) among Finnish PAH patients is poorly understood. We adopted a novel-targeted next-generation sequencing (NGS) approach called Oligonucleotide-Selective Sequencing (OS-Seq) and developed a custom data analysis and interpretation pipeline to identify pathogenic base substitutions, insertions, and deletions in seven genes associated with PAH (BMPR2, BMPR1B, ACVRL1, ENG, SMAD9, CAV1, and KCNK3) from Finnish PAH patients. This study represents the first clinical study with OS-Seq technology on patients suffering from a rare genetic disorder. We analyzed DNA samples from 21 Finnish PAH patients, whose BMPR2 and ACVRL1 mutation status had been previously studied using Sanger sequencing. Our sequencing panel covered 100% of the targeted base pairs with >15× sequencing depth. Pathogenic base substitutions were identified in the BMPR2 gene in 29% of the Finnish PAH cases. Two of the pathogenic variant-positive patients had been previously tested negative using Sanger sequencing. No clinically significant variants were identified in the six other PAH genes. Our study validates the use of targeted OS-Seq for genetic diagnostics of PAH and revealed pathogenic variants that had been previously missed using Sanger sequencing. PMID:26247051

  4. The ability of trainee general practitioners to identify psychological distress among their patients.

    PubMed

    Goldberg, D P; Jenkins, L; Millar, T; Faragher, E B

    1993-02-01

    It is argued that a general practitioner's ability to make accurate ratings of psychological distress is partly determined by the rate at which patients emit cues that are indicative of such distress. This study addresses the behaviours of doctors which influence the rates at which patients emit such cues. Consultations were videotaped involving six General Practice Vocational Trainees, three of them poor, and three of them able identifiers of emotional illness. Consultations were selected so that each trainee was rated interviewing 4 patients with low GHQ scores, and 4 patients with high scores. Behaviours are described which lead to increased cue emission and which are also practised more frequently by able identifiers, while other behaviours reduce cue emission and are practised less frequently by them. Another set of behaviours is no more frequent among the able identifiers, but when practised by able identifiers is associated with increased cue emission by the patients, and when practised by poor identifiers with unaltered or decreased cue emission. Interviews that are 'patient-led' are associated with increased rates of cue emission, while those that are 'doctor-led' are associated with lower rates. The implications of these findings for training doctors working in general medical settings are discussed. PMID:8475207

  5. 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

  6. Blood pressure measurement for accurate assessment of patient status in emergency medical settings.

    PubMed

    Convertino, Victor A

    2012-06-01

    Obtaining blood pressure measurements with traditional sphygomanometry that are insensitive and nonspecific can fail to provide an accurate assessment of patient status, particularly in specific clinical scenarios of acute reduction in central blood volume such as hemorrhage or orthostatic testing. This paper provides a review of newly emerging monitoring technologies that are being developed and integrated to improve patient diagnosis by using collection and feature extraction in real time of arterial waveforms by machine-learning algorithms. With assessment of continuous, noninvasively measured arterial waveforms, machine-learning algorithms have been developed with the capability to predict cardiovascular collapse with > 96% accuracy and a correlation of 0.89 between the time of predicted and actual cardiovascular collapse (e.g., shock, syncope) using a human model of progressive central hypovolemia. The resulting capability to obtain earlier predictions of imminent hemodynamic instability has significant implications for effective countermeasure applications by the aeromedical community. The ability to obtain real-time, continuous information about changes in features and patterns of arterial waveforms in addition to standard blood pressure provides for the first time the capability to assess the status of circulatory blood volume of the patient and can be used to diagnose progression toward development of syncope or overt shock, or guide fluid resuscitation. PMID:22764618

  7. 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

  8. Patient Identified Disease Burden in Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Johnson, Nicholas E; Quinn, Christine; Eastwood, Eileen; Tawil, Rabi; Heatwole, Chad R

    2013-01-01

    Introduction The multitude of symptoms associated with facioscapulohumeral muscular dystrophy (FSHD) disease burden are of varying importance. The extent of these symptoms and their cumulative effect on the FSHD population is unknown. Methods We conducted interviews with adult FSHD patients to identify which symptoms have the greatest effect on their lives. Each interview was recorded, transcribed, coded, and analyzed using a qualitative framework technique, triangulation, and 3-investigator consensus approach. Results 1375 quotes were obtained through 20 patient interviews. 251 symptoms of importance were identified representing 14 themes of FSHD disease burden. Symptoms associated with mobility impairment, activity limitation, and social role limitation were most frequently mentioned by participants. Conclusions There are multiple themes and symptoms, some previously under-recognized, that play a key role in FSHD disease burden. PMID:23225386

  9. Unilateral Prostate Cancer Cannot be Accurately Predicted in Low-Risk Patients

    SciTech Connect

    Isbarn, Hendrik; Karakiewicz, Pierre I.; Vogel, Susanne

    2010-07-01

    Purpose: Hemiablative therapy (HAT) is increasing in popularity for treatment of patients with low-risk prostate cancer (PCa). The validity of this therapeutic modality, which exclusively treats PCa within a single prostate lobe, rests on accurate staging. We tested the accuracy of unilaterally unremarkable biopsy findings in cases of low-risk PCa patients who are potential candidates for HAT. Methods and Materials: The study population consisted of 243 men with clinical stage {<=}T2a, a prostate-specific antigen (PSA) concentration of <10 ng/ml, a biopsy-proven Gleason sum of {<=}6, and a maximum of 2 ipsilateral positive biopsy results out of 10 or more cores. All men underwent a radical prostatectomy, and pathology stage was used as the gold standard. Univariable and multivariable logistic regression models were tested for significant predictors of unilateral, organ-confined PCa. These predictors consisted of PSA, %fPSA (defined as the quotient of free [uncomplexed] PSA divided by the total PSA), clinical stage (T2a vs. T1c), gland volume, and number of positive biopsy cores (2 vs. 1). Results: Despite unilateral stage at biopsy, bilateral or even non-organ-confined PCa was reported in 64% of all patients. In multivariable analyses, no variable could clearly and independently predict the presence of unilateral PCa. This was reflected in an overall accuracy of 58% (95% confidence interval, 50.6-65.8%). Conclusions: Two-thirds of patients with unilateral low-risk PCa, confirmed by clinical stage and biopsy findings, have bilateral or non-organ-confined PCa at radical prostatectomy. This alarming finding questions the safety and validity of HAT.

  10. 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. PMID:26511424

  11. Is clinical examination an accurate indicator of raised intra-abdominal pressure in critically injured patients?

    PubMed Central

    Kirkpatrick, Andrew W.; Brenneman, Frederick D.; McLean, Richard F.; Rapanos, Theodore; Boulanger, Bernard R.

    2000-01-01

    Objectives To determine the rate of elevated intra-abdominal pressure (IAP) and to evaluate the accuracy of clinical abdominal examination in the assessment of IAP in the critically injured trauma patient. Design A prospective blinded study. Setting The medical-surgical critical care unit of a university-affiliated regional adult trauma centre. Patients Forty-two adult blunt trauma victims, who had a mean injury severity score of 36. Interventions Urinary bladder pressure was measured daily and classified as normal (10 mm Hg or less), elevated (more than 10 mm Hg) or significantly elevated (more than 15 mm Hg). A blinded clinical assessment of abdominal pressure was concurrently performed and recorded as elevated or normal. Main outcome measures The sensitivity, specificity and accuracy and the positive and negative predictive values of the 2 interventions in identifying elevated IAP. Results Twenty-one patients (50%) had an elevated IAP at some point during the study. Of the 147 bladder pressure measurements done in these 42 patients, 47 (32%) were more than 10 mm Hg and 16 (11%) were more than 15 mm Hg. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of clinical abdominal examination for identifying elevated IAP were 40%, 94%, 76%, 77% and 77%, respectively. Clinical abdominal examination had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 56%, 87%, 35%, 94% and 84% respectively, for significantly elevated IAP. Conclusions Urinary bladder pressure was commonly elevated among our population of critically injured adults. Compared with bladder pressure measurements, clinical abdominal assessment showed poor sensitivity and accuracy for elevated IAP. These findings suggest that more routine measurements of bladder pressure in patients at risk for intra-abdominal hypertension should be performed. PMID:10851415

  12. Abdominal MRI without Enteral Contrast Accurately Detects Intestinal Fibrostenosis in Patients with Inflammatory Bowel Disease.

    PubMed

    Fisher, Jeremy G; Kalb, Bobby; Martin, Diego; Dhere, Tanvi; Perez, Sebastian D; Srinivasan, Jahnavi K

    2015-11-01

    Patients with inflammatory bowel disease (IBD) presenting for surgical evaluation require thorough small bowel surveillance as it improves accuracy of diagnosis (ulcerative colitis versus Crohn's) and differentiates those who may respond to nonoperative therapy, preserving bowel length. MRI has not been validated conclusively against histopathology in IBD. Most protocols require enteral contrast. This study aimed to 1) evaluate the accuracy of MRI for inflammation, fibrosis, and extraluminal complications and 2) compare MRI without enteral contrast to standard magnetic resonance enterography. Adults with Crohn's disease or ulcerative colitis who underwent abdominal MRI and surgery were retrospectively reviewed. Of 65 patients evaluated, 55 met inclusion criteria. Overall sensitivity and specificity of MRI for disease involvement localized by segment were 93 per cent (95% confidence interval = 89.4-95.0) and 95 per cent (95% confidence interval = 92.3-97.0), respectively (positive predictive value was 86%, negative predictive value was 98%). Sensitivity and specificity between MRI with and without oral and rectal contrast were similar (96% vs 91% and 99% vs 94%, P > 0.10). As were positive predictive value and negative predictive value (85% vs 96%, P = 0.16; 97% vs 99%, P = 0.42). Magnetic resonance is highly sensitive and specific for localized disease involvement and extraluminal abdominal sequelae of IBD. It accurately differentiates patients who have chronic transmural (fibrotic) disease and thus may require an operation from those with acute inflammation, whose symptoms may improve with aggressive medical therapy alone. MRI without contrast had comparable diagnostic yield to standard magnetic resonance enterography. PMID:26672581

  13. 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

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

    PubMed

    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

    2015-05-30

    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

  15. 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

  16. ZCURVE 3.0: identify prokaryotic genes with higher accuracy as well as automatically and accurately select essential genes.

    PubMed

    Hua, Zhi-Gang; Lin, Yan; Yuan, Ya-Zhou; Yang, De-Chang; Wei, Wen; Guo, Feng-Biao

    2015-07-01

    In 2003, we developed an ab initio program, ZCURVE 1.0, to find genes in bacterial and archaeal genomes. In this work, we present the updated version (i.e. ZCURVE 3.0). Using 422 prokaryotic genomes, the average accuracy was 93.7% with the updated version, compared with 88.7% with the original version. Such results also demonstrate that ZCURVE 3.0 is comparable with Glimmer 3.02 and may provide complementary predictions to it. In fact, the joint application of the two programs generated better results by correctly finding more annotated genes while also containing fewer false-positive predictions. As the exclusive function, ZCURVE 3.0 contains one post-processing program that can identify essential genes with high accuracy (generally >90%). We hope ZCURVE 3.0 will receive wide use with the web-based running mode. The updated ZCURVE can be freely accessed from http://cefg.uestc.edu.cn/zcurve/ or http://tubic.tju.edu.cn/zcurveb/ without any restrictions. PMID:25977299

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

    PubMed

    Sowers, Sun B; 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

    2016-08-01

    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

  18. 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

  19. 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

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

    PubMed

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

    2011-01-01

    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

  1. Is this the right patient? An educational initiative to improve compliance with two patient identifiers.

    PubMed

    Mollon, Deene' L; Fields, Willa L

    2009-05-01

    A rehabilitation nursing unit implemented an educational initiative to improve compliance with two patient identifiers. The education consisted of a poster presentation and then, 2 months later, a mandatory in-service education program. Compliance with two patient identifiers improved, although more improvement was demonstrated after the mandatory in-service. The results of this performance improvement project suggest that investing time and money in safety initiatives improves staff practice patterns. PMID:19489521

  2. 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. PMID:18579831

  3. My patient is injured: identifying foreign bodies with ultrasound.

    PubMed

    Lewis, David; Jivraj, Aman; Atkinson, Paul; Jarman, Robert

    2015-08-01

    Patients commonly present to the emergency department with a suspected retained foreign body, following penetrating injury. While plain radiography is often the first line in identifying radio-opaque foreign bodies, radiolucent foreign bodies such as wood and plastic can easily be missed. Furthermore, real-time visualization of such a foreign body can assist in its removal. This article evaluates the use of point-of-care ultrasound by emergency physicians in the identification and removal of soft-tissue foreign bodies along with describing the appropriate technique and highlighting the potential pitfalls. An illustrated case example is presented that highlights the benefits of point-of-care ultrasound foreign body detection and guided removal. PMID:27433254

  4. My patient has abdominal and flank pain: Identifying renal causes.

    PubMed

    Cox, Christopher; MacDonald, Scott; Henneberry, Ryan; Atkinson, Paul R

    2015-11-01

    Acute flank and abdominal pain are common presenting complaints in the emergency department. With increasing access to point-of-care ultrasound (PoCUS), emergency physicians have an added tool to help identify renal problems as a cause of a patient's pain. PoCUS for hydronephrosis has a sensitivity of 72-83.3% and a varying specificity, similar to radiology-performed ultrasonography. In addition to assessment for hydronephrosis, PoCUS can help emergency physicians to exclude other serious causes of flank and abdominal pain such as the presence of an abdominal aortic aneurysm, or free fluid in the intraperitoneal space, which could represent hemorrhage. Use of PoCUS for the assessment of flank pain has resulted in more rapid diagnosis, decreased use of computed tomography, and shorter emergency department length of stay. PMID:27433264

  5. My patient has got abdominal pain: identifying biliary problems

    PubMed Central

    Taylor, Mark; Loubani, Osama; Bowra, Justin; Atkinson, Paul

    2014-01-01

    Right upper quadrant and epigastric abdominal pain are common presenting complaints in the emergency department. With increasing access to point-of-care ultrasound, emergency physicians now have an added tool to help identify biliary problems as a cause of a patient’s right upper quadrant pain. Point-of-care ultrasound has a sensitivity of 89.8% (95% CI 86.4–92.5%) and specificity of 88.0% (83.7–91.4%) for cholelithiasis, very similar to radiology-performed ultrasonography. In addition to assessment for cholelithiasis and cholecystitis, point-of-care ultrasound can help emergency physicians to determine whether the biliary system is the source of infection in patients with suspected sepsis. Use of point-of-care ultrasound for the assessment of the biliary system has resulted in more rapid diagnosis, decreasing costs, and shorter emergency department length of stay.

  6. Identifying patient smoking status from medical discharge records.

    PubMed

    Uzuner, Ozlem; Goldstein, Ira; Luo, Yuan; Kohane, Isaac

    2008-01-01

    The authors organized a Natural Language Processing (NLP) challenge on automatically determining the smoking status of patients from information found in their discharge records. This challenge was issued as a part of the i2b2 (Informatics for Integrating Biology to the Bedside) project, to survey, facilitate, and examine studies in medical language understanding for clinical narratives. This article describes the smoking challenge, details the data and the annotation process, explains the evaluation metrics, discusses the characteristics of the systems developed for the challenge, presents an analysis of the results of received system runs, draws conclusions about the state of the art, and identifies directions for future research. A total of 11 teams participated in the smoking challenge. Each team submitted up to three system runs, providing a total of 23 submissions. The submitted system runs were evaluated with microaveraged and macroaveraged precision, recall, and F-measure. The systems submitted to the smoking challenge represented a variety of machine learning and rule-based algorithms. Despite the differences in their approaches to smoking status identification, many of these systems provided good results. There were 12 system runs with microaveraged F-measures above 0.84. Analysis of the results highlighted the fact that discharge summaries express smoking status using a limited number of textual features (e.g., "smok", "tobac", "cigar", Social History, etc.). Many of the effective smoking status identifiers benefit from these features. PMID:17947624

  7. 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. PMID:26262127

  8. How Accurate Are Patients at Diagnosing the Cause of Their Knee Pain With the Help of a Web-based Symptom Checker?

    PubMed Central

    Bisson, Leslie J.; Komm, Jorden T.; Bernas, Geoffrey A.; Fineberg, Marc S.; Marzo, John M.; Rauh, Michael A.; Smolinski, Robert J.; Wind, William M.

    2016-01-01

    Background: Researching medical information is the third most popular activity online, and there are a variety of web-based symptom checker programs available. Purpose: This study evaluated a patient’s ability to self-diagnose their knee pain from a list of possible diagnoses supplied by an accurate symptom checker. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: All patients older than 18 years who presented to the office of 7 different fellowship-trained sports medicine surgeons over an 8-month period with a complaint of knee pain were asked to participate. A web-based symptom checker for knee pain was used; the program has a reported accuracy of 89%. The symptom checker generates a list of potential diagnoses after patients enter symptoms and links each diagnosis to informative content. After exploring the informative content, patients selected all diagnoses they felt could explain their symptoms. Each patient was later examined by a physician who was blinded to the differential generated by the program as well as the patient-selected diagnoses. A blinded third party compared the diagnoses generated by the program with those selected by the patient as well as the diagnoses determined by the physician. The level of matching between the patient-selected diagnoses and the physician’s diagnoses determined the patient’s ability to correctly diagnose their knee pain. Results: There were 163 male and 165 female patients, with a mean age of 48 years (range, 18-76 years). The program generated a mean 6.6 diagnoses (range, 2-15) per patient. Each patient had a mean 1.7 physician diagnoses (range, 1-4). Patients selected a mean 2 diagnoses (range, 1-9). The patient-selected diagnosis matched the physician’s diagnosis 58% of the time. Conclusion: With the aid of an accurate symptom checker, patients were able to correctly identify the cause of their knee pain 58% of the time. PMID:26962542

  9. 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

  10. A 6 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis B.

    PubMed

    Xu, Ming-Yi; Qu, Ying; Li, Zhenghong; Li, Fei; Xiao, Chun-Yang; Lu, Lun-Gen

    2016-01-01

    Clinical factors and liver biopsy cannot accurately predict the risk of developing cirrhosis in chronic hepatitis B (CHB).This study was to develop a predictive gene signature for cirrhosis in CHB patients. A total of 183 untreated CHB patients were enrolled. GeneChip, significant analysis of microarray (SAM) and prediction analysis of microarray (PAM) were used to select predictor genes (PGs) in liver tissues. The Cirrhosis Risk Score (CRS) was calculated based on 6 PG variables and the predictive value of CRS was evaluated. Firstly differentially expressed genes were filtered from a genome scan and SAM, and 87 significant genes were selected for the signature building. Secondly a signature consisting of 6 PGs (CD24, CXCL6, EHF, ITGBL1, LUM and SOX9) most predictive for cirrhosis risk in CHB patients was developed in the selection set (n=40) by use of PAM and PCR approach. Finally the CRS was calculated to estimate the risk of developing cirrhosis and then tested in validation cohort (n=143). The area under the ROC curves (AUROC) of the CRS was 0.944 and exceeded to 6 PGs and clinical factors. A low CRS cutoff of 6.43 to identify low-risk patients would misclassify only 8.16% of high-risk patients, while a high cutoff of 8.32 to identify high-risk patients would misclassify 0% of low-risk patients. So CRS is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis and application of CRS in clinical practice could help to reduce the rate of liver biopsy in patients with CHB. PMID:26709788

  11. Identifying patients at risk of type 2 diabetes.

    PubMed

    Savill, Peter

    2012-01-01

    At present there are nearly 3 million people with diabetes in the UK. It is predicted that this number will almost double by 2025. Nine out of ten of these individuals will have type 2 diabetes. It is estimated that one in seven adults have impaired glucose regulation and up to 12% of these will develop type 2 diabetes each year. The impact of obesity on the development of type 2 diabetes cannot be overemphasised, with a 1 kg/m2 increase in BMI raising the risk of impaired fasting glycaemia by 9.5% and of developing new-onset type 2 diabetes by 8.4%. A 1 cm increase in waist circumference increases the risks by 3.2% and 3.5% respectively. NICE advises using a validated risk assessment tool to identify patients at risk of diabetes. Risk factors used by such tools include: age; ethnicity; weight; first-degree relative with type 2 diabetes; low birthweight and sedentary lifestyle. Certain comorbidities increase the risk of type 2 diabetes, these include: cardiovascular and cerebrovascular disease; polycystic ovary syndrome; a history of gestational diabetes; and mental health problems. The initial screening blood test could be a fasting plasma glucose, HbA1c, or an oral glucose tolerance test, according to WHO criteria. NICE recommends that high-risk patients should be offered a programme encouraging them to undertake a minimum of 150 minutes of moderate intensity physical activity a week, gradually lose weight to reach and maintain a BMI within the healthy range, increase consumption of whole grains, vegetables, and other foods that are high in dietary fibre, reduce the total amount of fat in their diet and eat less saturated fat. PMID:22988703

  12. Identifying patients at risk of perinatal mood disorders.

    PubMed

    Topiwala, Anya; Hothi, Gurjiven; Ebmeier, Klaus P

    2012-05-01

    Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term emotional and cognitive development of the child. Psychiatric disorders have consistently been found to be one of the leading causes of maternal deaths, often through suicide. Postnatal depression and puerperal psychosis are two disorders most commonly associated with the perinatal period. The most efficient strategy to identify patients at risk relies on focussing on clinically vulnerable subgroups: enquiries about depressive symptoms should be made at the usual screening visits. Attention should be paid to any sign of poor self-care, avoidance of eye contact, overactivity or underactivity, or abnormalities in the rate of speech. Particular care should be taken to ask about suicidal ideation and thoughts of harming others, including the baby. One of the most important risk factors is a previous history of depression. The degree of risk is directly correlated with severity of past episodes. Both antenatal and postnatal depression are being increasingly recognised in men. Puerperal psychosis is rare (1 to 2 per 1,000). Sixty per cent of women with puerperal psychosis already have a diagnosis of bipolar disorder or schizoaffective disorder. Women with a personal history of postpartum psychosis or bipolar affective disorder should be considered as high risk for postpartum psychosis. All pregnant women who are identified as being at high risk should have a shared care plan for their late pregnancy and early postnatal psychiatric management. Women with current mood disorder of mild or moderate severity who have a first-degree relative with a history of bipolar disorder or postpartum psychosis should be referred for psychiatric assessment. PMID:22774377

  13. Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts

    PubMed Central

    Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

    2016-01-01

    Introduction: Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. Objective: To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. Methods: We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. Results: We identified 721 CDIs following 54,186 hospital admissions—a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Conclusion: Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning. PMID:26845084

  14. Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes

    PubMed Central

    Lieberman, Tami D.; Michel, Jean-Baptiste; Aingaran, Mythili; Potter-Bynoe, Gail; Roux, Damien; Davis, Michael R.; Skurnik, David; Leiby, Nicholas; LiPuma, John J.; Goldberg, Joanna B.; McAdam, Alexander J.; Priebe, Gregory P.; Kishony, Roy

    2011-01-01

    Bacterial pathogens evolve during the infection of their human hosts1-8, but separating adaptive and neutral mutations remains challenging9-11. Here, we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple patients. We conducted a retrospective study of a Burkholderia dolosa outbreak among people with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired non-synonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes illuminate the genetic basis of important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition, and implicate oxygen-dependent gene regulation as paramount in lung infections. Several genes have not been previously implicated in pathogenesis, suggesting new therapeutic targets. The identification of parallel molecular evolution suggests key selection forces acting on pathogens within humans and can help predict and prepare for their future evolutionary course. PMID:22081229

  15. 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. PMID:25615567

  16. Identification of a 251 Gene Expression Signature That Can Accurately Detect M. tuberculosis in Patients with and without HIV Co-Infection

    PubMed Central

    Dawany, Noor; Showe, Louise C.; Kossenkov, Andrew V.; Chang, Celia; Ive, Prudence; Conradie, Francesca; Stevens, Wendy; Sanne, Ian

    2014-01-01

    Background Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV. Methods We analyzed global gene expression data from peripheral blood mononuclear cell (PBMC) samples of patients that were either mono-infected with HIV or co-infected with HIV/TB and used support vector machines to identify a gene signature that can distinguish between the two classes. We then validated our results using publically available gene expression data from patients mono-infected with TB. Results Our analysis successfully identified a 251-gene signature that accurately distinguishes patients co-infected with HIV/TB from those infected with HIV only, with an overall accuracy of 81.4% (sensitivity = 76.2%, specificity = 86.4%). Furthermore, we show that our 251-gene signature can also accurately distinguish patients with active TB in the absence of an HIV infection from both patients with a latent TB infection and healthy controls (88.9–94.7% accuracy; 69.2–90% sensitivity and 90.3–100% specificity). We also demonstrate that the expression levels of the 251-gene signature diminish as a correlate of the length of TB treatment. Conclusions A 251-gene signature is described to (a) detect TB in the presence or absence of an HIV co-infection, and (b) assess response to treatment following anti-TB therapy. PMID:24587128

  17. Screening for Patients with Alcohol Problems: Severity of Patients Identified by the CAGE.

    ERIC Educational Resources Information Center

    Lairson, David R.; And Others

    1992-01-01

    Assessed CAGE (first letters of keywords in series of 4 questions about drinking: cut down, annoyed, guilty, eye-opener), instrument in routine screening for alcohol problems among 687 patients of 2 primary care physicians. Results showed that CAGE instrument was useful screening device for identifying those with mild to moderate substance abuse…

  18. 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. PMID:27134610

  19. 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

  20. 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. PMID:26886109

  1. Patients with chronic fatigue syndrome and accurate feeling-of-knowing judgments.

    PubMed

    Lakein, D A; Fantie, B D; Grafman, J; Ross, S; O'Fallon, A; Dale, J; Straus, S E

    1997-11-01

    Many Chronic Fatigue Syndrome (CFS) patients complain of memory impairments which have been difficult to document empirically. Subjective complaints of memory impairment may be due to a deficit in metamemory judgment. CFS patients and matched controls were tested with a computerized Trivia Information Quiz that required them to rate their confidence about correctly recognizing an answer in a multiple choice format that they had been unable to remember in a fact-recall format. Even though CFS patients reported significantly greater amounts of fatigue, cognitive, and physical symptoms, the accuracy of their confidence levels and recognition responses were similar to controls. This finding suggests that a metamemory deficit is not the cause of the memory problems reported by CFS patients. PMID:9356893

  2. Making the most of your prognostic factors: presenting a more accurate survival model for breast cancer patients.

    PubMed

    Knorr, K L; Hilsenbeck, S G; Wenger, C R; Pounds, G; Oldaker, T; Vendely, P; Pandian, M R; Harrington, D; Clark, G M

    1992-01-01

    Determining an appropriate level of adjuvant therapy is one of the most difficult facets of treating breast cancer patients. Although the myriad of prognostic factors aid in this decision, often they give conflicting reports of a patient's prognosis. What we need is a survival model which can properly utilize the information contained in these factors and give an accurate, reliable account of the patient's probability of recurrence. We also need a method of evaluating these models' predictive ability instead of simply measuring goodness-of-fit, as is currently done. Often, prognostic factors are broken into two categories such as positive or negative. But this dichotomization may hide valuable prognostic information. We investigated whether continuous representations of factors, including standard transformations--logarithmic, square root, categorical, and smoothers--might more accurately estimate the underlying relationship between each factor and survival. We chose the logistic regression model, a special case of the commonly used Cox model, to test our hypothesis. The model containing continuous transformed factors fit the data more closely than the model containing the traditional dichotomized factors. In order to appropriately evaluate these models, we introduce three predictive validity statistics--the Calibration score, the Overall Calibration score, and the Brier score--designed to assess the model's accuracy and reliability. These standardized scores showed the transformed factors predicted three year survival accurately and reliably. The scores can also be used to assess models or compare across studies. PMID:1391991

  3. 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

  4. 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.

  5. 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

  6. 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…

  7. 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. PMID:26819226

  8. 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

  9. 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. PMID:23349514

  10. Underreporting of patient safety incidents reduces health care's ability to quantify and accurately measure harm reduction.

    PubMed

    Noble, Douglas J; Pronovost, Peter J

    2010-12-01

    Underreporting of patient safety incidents creates a reservoir of information that is plagued with epidemiological bias. These include systematic biases such as the practice of reporting minor incidents at the expense of more serious ones. This leads to inaccurate rates of errors and an inability to generalize results to whole patient populations. It leaves reporting incidents, in epidemiological terms, comparable to nonrandom samples from an unknown universe of events. These epidemiological problems lead to a situation where priorities are skewed toward what "we know we know." As "we know what we do not know," for example, gaps in knowledge about serious incidents due to low reporting rates, due caution must be applied in making policy based on biased underreporting. Barriers to reporting contribute to low participation rates and further bias information. Lack of feedback and fear of personal consequences are common barriers. Evaluation of reporting systems indicates reports can be used as tools for learning, but it is not yet possible to monitor improvement in patient safety or measurably prove reduction in harm. Mandatory reporting makes sense from an epidemiological point of view, but there are legitimate fears that it could further reduce reporting rates due to fear of reprisal. Underreporting and the associated biases are a significant problem in realizing the epidemiological potential of incident reporting in health care. PMID:21500613

  11. 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

    2015-01-01

    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

  12. 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

  13. The Identified Patient and Stage of Family Development.

    ERIC Educational Resources Information Center

    Fishbein, Harold D.

    1982-01-01

    Assesses relationships between child vulnerability to stress, birth order, and stage of family development. Identified four stages of family structure. Results showed vulnerability of first-borns and last-borns shifted across stages in a complementary fashion. Interpreted results in terms of a linkage between emotional symptoms and family…

  14. Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis

    PubMed Central

    Ascha, Mona; Wang, Zeneng; Ascha, Mustafa S; Dweik, Raed; Zein, Nizar N; Grove, David; Brown, J Mark; Marshall, Stephanie; Lopez, Rocio; Hanouneh, Ibrahim A

    2016-01-01

    AIM: To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH). METHODS: We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival. RESULTS: A comparison of model for end-stage liver disease (MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD (area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54 (0.18, 0.91); P = 0.005], homocitrulline [0.66 (0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53 (0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers (carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH. CONCLUSION

  15. Network Modeling Identifies Patient-specific Pathways in Glioblastoma

    PubMed Central

    Tuncbag, Nurcan; Milani, Pamela; Pokorny, Jenny L.; Johnson, Hannah; Sio, Terence T.; Dalin, Simona; Iyekegbe, Dennis O.; White, Forest M.; Sarkaria, Jann N.; Fraenkel, Ernest

    2016-01-01

    Glioblastoma is the most aggressive type of malignant human brain tumor. Molecular profiling experiments have revealed that these tumors are extremely heterogeneous. This heterogeneity is one of the principal challenges for developing targeted therapies. We hypothesize that despite the diverse molecular profiles, it might still be possible to identify common signaling changes that could be targeted in some or all tumors. Using a network modeling approach, we reconstruct the altered signaling pathways from tumor-specific phosphoproteomic data and known protein-protein interactions. We then develop a network-based strategy for identifying tumor specific proteins and pathways that were predicted by the models but not directly observed in the experiments. Among these hidden targets, we show that the ERK activator kinase1 (MEK1) displays increased phosphorylation in all tumors. By contrast, protein numb homolog (NUMB) is present only in the subset of the tumors that are the most invasive. Additionally, increased S100A4 is associated with only one of the tumors. Overall, our results demonstrate that despite the heterogeneity of the proteomic data, network models can identify common or tumor specific pathway-level changes. These results represent an important proof of principle that can improve the target selection process for tumor specific treatments. PMID:27354287

  16. The index of orthognathic functional treatment need accurately prioritises those patients already selected for orthognathic surgery within the NHS.

    PubMed

    Shah, Rupal; Breeze, John; Chand, Mohit; Stockton, Peter

    2016-06-01

    The index of orthognathic functional treatment need (IOFTN) is a newly-proposed system to help to prioritise patients for orthognathic treatment. The five categories are similar to those used in orthodontics, but include additional parameters such as sleep apnoea and facial asymmetry. The aim of this audit was to validate the index and find out the potential future implications, should such a system ever be adopted by commissioners. We calculated the IOFTN category of 100 consecutive patients who had orthognathic surgery between 2010-14 using clinical notes, photographs, study models, and radiographs, and determined the number in categories 4 or 5, analogous to the current indications for orthodontic treatment within the NHS. Sufficient clinical information was available to categorise 59/100 patients, and 56 of the 59 (95%) were in either category 4 or 5. All three of the remaining patients (in categories 1-3) who were operated on were treated because of the anticipated favourable impact on their quality of life. The IOFTN has been proposed for use in future commissioning of orthognathic services within the NHS, and this study has confirmed its efficacy in prioritising treatment accurately, with 95% of patients being in categories 4 or 5. We recommend that the orthognathic treatment index be adapted to include additional psychosocial assessment so that patients who fall into the lower functional categories are not automatically excluded from this potentially life-changing treatment. PMID:26935212

  17. The Patient Information Advisory Group and the use of patient-identifiable data.

    PubMed

    Higgins, Joan

    2003-07-01

    Patient confidentiality has been a matter of concern in the English National Health Service (NHS) for many years. A number of recent events have triggered the demand for a more concerted programme of change to eliminate the use of patient-identifiable data and to devise more acceptable alternatives. The Caldicott Committee, in 1997, set out the case for change and legislation in 1998 (the Data Protection Act and Human Rights Act) and emphasised the need for urgent action. A number of public inquiries into failures of care in the NHS (at Bristol Royal Infirmary and Alder Hey Hospital) pointed to the failure to seek consent as a major issue for the NHS. Whilst accepting the need for change, the Government, in drafting the Health and Social Care Act 2001, allowed for the fact that some organisations and individuals would need time to move towards anonymisation of data (reversible or irreversible) or to obtain patient consent. Under Section 60 of the Act it established the Patient Information Advisory Group (PIAG). PIAG advises government ministers on circumstances in which the continued use of patient-identifiable data should be permitted, as a temporary measure. PIAG faces a number of challenges as it develops its programme of work: how to maintain the pace of change towards anonymisation, how to ensure compliance with the law, how or whether to share information across organisational boundaries in the interests of citizens, how consent should be obtained and how to achieve 'joined up' working across those organisations that are charged with promoting confidentiality and privacy. PMID:12869331

  18. Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease.

    PubMed Central

    Etcheberrigaray, R; Ito, E; Oka, K; Tofel-Grehl, B; Gibson, G E; Alkon, D L

    1993-01-01

    Since memory loss is characteristic of Alzheimer disease (AD), and since K+ channels change during acquisition of memory in both molluscs and mammals, we investigated K+ channel function as a possible site of AD pathology and, therefore, as a possible diagnostic index as well. A 113-pS tetraethylammonium (TEA)-sensitive K+ channel was consistently absent from AD fibroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invariable absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2+ signal indicate K+ channel dysfunction in AD fibroblasts. These results suggest the possibility of a laboratory method that would diagnostically distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD neurological and psychiatric disorders. PMID:8367484

  19. Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening: Removing the Confounder of Discordance

    PubMed Central

    Gajjar, Ketan; Ahmadzai, Abdullah A.; Valasoulis, George; Trevisan, Júlio; Founta, Christina; Nasioutziki, Maria; Loufopoulos, Aristotelis; Kyrgiou, Maria; Stasinou, Sofia Melina; Karakitsos, Petros; Paraskevaidis, Evangelos; Da Gama-Rose, Bianca; Martin-Hirsch, Pierre L.; Martin, Francis L.

    2014-01-01

    Background Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. Methods Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn’s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. Results Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening

  20. Patient Safety Indicators: using administrative data to identify potential patient safety concerns.

    PubMed Central

    Miller, M R; Elixhauser, A; Zhan, C; Meyer, G S

    2001-01-01

    OBJECTIVE: To develop Patient Safety Indicators (PSI) to identify potential in-hospital patient safety problems for the purpose of quality improvement. DATA SOURCE/STUDY DESIGN: The data source was 2,400,000 discharge records in the 1997 New York State Inpatient Database. PSI algorithms were developed using systematic literature reviews of indicators and hand searches of the ICD-9-CM code book. The prevalence of PSI events and associations between PSI events and patient-level and hospital-level characteristics, length of stay, in-hospital mortality, and hospital charges were examined. PRINCIPAL FINDINGS: PSIs were developed for 12 distinct clinical situations and an overall summary measure. The 1997 event rates per 10,000 discharges varied from 1.1 for foreign bodies left during procedure to 84.7 for birth traumas. Discharge records with PSI events had twofold to threefold longer hospital stays, twofold to 20-fold higher rates of in-hospital mortality, and twofold to eightfold higher total charges than records without PSI events. Multivariate logistic regression revealed that PSI events were primarily associated with increasing age (p < .001), hospitals performing more inpatient surgery (p < .001), and hospitals with higher percentage of beds in intensive care units (p < .001). CONCLUSIONS: The PSIs provide an efficient and user-friendly tool to identify potential inhospital patient safety problems for targeted institution-level quality improvement efforts. Until better error-reporting systems are developed the PSIs can serve to shed light on the problem of medical errors not limited solely to mortality because of errors. PMID:16148964

  1. [Expression of bioinformatically identified genes in skin of psoriasis patients].

    PubMed

    Sobolev, V V; Nikol'skaia, T A; Zolotarenko, A D; Piruzian, E S; Bruskin, S A

    2013-10-01

    Gene expression analysis for EPHA2 (EPH receptor A2), EPHB2 (EPH receptor B2), S100A9 (S100 calcium binding protein A9), PBEF(nicotinamide phosphoribosyltransferase), LILRB2 (leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 2), PLAUR (plasminogen activator, urokinase receptor), LTB (lymphotoxin beta (TNF superfamily, member 3)), WNT5A (wingless-type MMTV integration site family, member 5A) has been conducted using real-time polymerase chain reaction in specimens affected by psoriasis versus visually intact skin in 18 patients. It was revealed that the expression of the nine examined genes was upregulated in the affected by psoriasis compared to visually intact skin specimens. The highest expression was observed for S100A9, S100AS, PBEF, WNT5A2, and EPHB2 genes. S100A9 and S100A8 gene expression in the affected by psoriasis skin was 100-fold higher versus visually intact skin while PBEF, WNT5A, and EPHB2 gene expression was upregulated more than five-fold. We suggested that the high expression of these genes might be associated with the state of the pathological process in psoriasis. Moreover, the transcriptional activity of these genes might serve a molecular indicator of the efficacy of treatment in psoriasis. PMID:25474898

  2. [Expression of bioinformatically identified genes in skin of psoriasis patients].

    PubMed

    2013-10-01

    Gene expression analysis for EPHA2 (EPH receptor A2), EPHB2 (EPH receptor B2), S100A9 (S100 calcium binding protein A9), PBEF(nicotinamide phosphoribosyltransferase), LILRB2 (leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 2), PLAUR (plasminogen activator, urokinase receptor), LTB (lymphotoxin beta (TNF superfamily, member 3)), WNT5A (wingless-type MMTV integration site family, member 5A) has been conducted using real-time polymerase chain reaction in specimens affected by psoriasis versus visually intact skin in 18 patients. It was revealed that the expression of the nine examined genes was upregulated in the affected by psoriasis compared to visually intact skin specimens. The highest expression was observed for S100A9, S100AS, PBEF, WNT5A2, and EPHB2 genes. S100A9 and S100A8 gene expression in the affected by psoriasis skin was 100-fold higher versus visually intact skin while PBEF, WNT5A, and EPHB2 gene expression was upregulated more than five-fold. We suggested that the high expression of these genes might be associated with the state of the pathological process in psoriasis. Moreover, the transcriptional activity of these genes might serve a molecular indicator of the efficacy of treatment in psoriasis. PMID:25508677

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Identifying medical terms in patient-authored text: a crowdsourcing-based approach

    PubMed Central

    MacLean, Diana Lynn; Heer, Jeffrey

    2013-01-01

    Background and objective As people increasingly engage in online health-seeking behavior and contribute to health-oriented websites, the volume of medical text authored by patients and other medical novices grows rapidly. However, we lack an effective method for automatically identifying medical terms in patient-authored text (PAT). We demonstrate that crowdsourcing PAT medical term identification tasks to non-experts is a viable method for creating large, accurately-labeled PAT datasets; moreover, such datasets can be used to train classifiers that outperform existing medical term identification tools. Materials and methods To evaluate the viability of using non-expert crowds to label PAT, we compare expert (registered nurses) and non-expert (Amazon Mechanical Turk workers; Turkers) responses to a PAT medical term identification task. Next, we build a crowd-labeled dataset comprising 10 000 sentences from MedHelp. We train two models on this dataset and evaluate their performance, as well as that of MetaMap, Open Biomedical Annotator (OBA), and NaCTeM's TerMINE, against two gold standard datasets: one from MedHelp and the other from CureTogether. Results When aggregated according to a corroborative voting policy, Turker responses predict expert responses with an F1 score of 84%. A conditional random field (CRF) trained on 10 000 crowd-labeled MedHelp sentences achieves an F1 score of 78% against the CureTogether gold standard, widely outperforming OBA (47%), TerMINE (43%), and MetaMap (39%). A failure analysis of the CRF suggests that misclassified terms are likely to be either generic or rare. Conclusions Our results show that combining statistical models sensitive to sentence-level context with crowd-labeled data is a scalable and effective technique for automatically identifying medical terms in PAT. PMID:23645553

  10. SU-E-T-475: An Accurate Linear Model of Tomotherapy MLC-Detector System for Patient Specific Delivery QA

    SciTech Connect

    Chen, Y; Mo, X; Chen, M; Olivera, G; Parnell, D; Key, S; Lu, W; Reeher, M; Galmarini, D

    2014-06-01

    Purpose: An accurate leaf fluence model can be used in applications such as patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is known that the total fluence is not a linear combination of individual leaf fluence due to leakage-transmission, tongue-and-groove, and source occlusion effect. Here we propose a method to model the nonlinear effects as linear terms thus making the MLC-detector system a linear system. Methods: A leaf pattern basis (LPB) consisting of no-leaf-open, single-leaf-open, double-leaf-open and triple-leaf-open patterns are chosen to represent linear and major nonlinear effects of leaf fluence as a linear system. An arbitrary leaf pattern can be expressed as (or decomposed to) a linear combination of the LPB either pulse by pulse or weighted by dwelling time. The exit detector responses to the LPB are obtained by processing returned detector signals resulting from the predefined leaf patterns for each jaw setting. Through forward transformation, detector signal can be predicted given a delivery plan. An equivalent leaf open time (LOT) sinogram containing output variation information can also be inversely calculated from the measured detector signals. Twelve patient plans were delivered in air. The equivalent LOT sinograms were compared with their planned sinograms. Results: The whole calibration process was done in 20 minutes. For two randomly generated leaf patterns, 98.5% of the active channels showed differences within 0.5% of the local maximum between the predicted and measured signals. Averaged over the twelve plans, 90% of LOT errors were within +/−10 ms. The LOT systematic error increases and shows an oscillating pattern when LOT is shorter than 50 ms. Conclusion: The LPB method models the MLC-detector response accurately, which improves patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is sensitive enough to detect systematic LOT errors as small as 10 ms.

  11. Why Are Some GCSE Examination Questions Harder to Mark Accurately than Others? Using Kelly's Repertory Grid Technique to Identify Relevant Question Features

    ERIC Educational Resources Information Center

    Suto, W. M. Irenka; Nadas, Rita

    2009-01-01

    It has long been established that marking accuracy in public examinations varies considerably among subjects and markers. This is unsurprising, given the diverse cognitive strategies that the marking process can entail, but what makes some questions harder to mark accurately than others? Are there distinct but subtle features of questions and…

  12. Identifying Patients in the Acute Psychiatric Hospital Who May Benefit From a Palliative Care Approach.

    PubMed

    Burton, M Caroline; Warren, Mark; Cha, Stephen S; Stevens, Maria; Blommer, Megan; Kung, Simon; Lapid, Maria I

    2016-04-01

    Identifying patients who will benefit from a palliative care approach is the first critical step in integrating palliative with curative therapy. Criteria are established that identify hospitalized medical patients who are near end of life, yet there are no criteria with respect to hospitalized patients with psychiatric disorders. The records of 276 consecutive patients admitted to a dedicated inpatient psychiatric unit were reviewed to identify prognostic criteria predictive of mortality. Mortality predictors were 2 or more admissions in the past year (P = .0114) and older age (P = .0006). Twenty-two percent of patients met National Hospice and Palliative Care Organization noncancer criteria for dementia. Palliative care intervention should be considered when treating inpatients with psychiatric disorders, especially older patients who have a previous hospitalization or history of dementia. PMID:25318929

  13. Identifying risk of hospital readmission among Medicare aged patients: an approach using routinely collected data.

    PubMed

    Navarro, Adria E; Enguídanos, Susan; Wilber, Kathleen H

    2012-01-01

    Readmission provisions in the Patient Protection and Affordable Care Act of March 2010 have created urgent fiscal accountability requirements for hospitals, dependent upon a better understanding of their specific populations, along with development of mechanisms to easily identify these at-risk patients. Readmissions are disruptive and costly to both patients and the health care system. Effectively addressing hospital readmissions among Medicare aged patients offers promising targets for resources aimed at improved quality of care for older patients. Routinely collected data, accessible via electronic medical records, were examined using logistic models of sociodemographic, clinical, and utilization factors to identify predictors among patients who required rehospitalization within 30 days. Specific comorbidities and discharge care orders in this urban, nonprofit hospital had significantly greater odds of predicting a Medicare aged patient's risk of readmission within 30 days. PMID:22656916

  14. Dual-Energy Head CT Enables Accurate Distinction of Intraparenchymal Hemorrhage from Calcification in Emergency Department Patients.

    PubMed

    Hu, Ranliang; Daftari Besheli, Laleh; Young, Joseph; Wu, Markus; Pomerantz, Stuart; Lev, Michael H; Gupta, Rajiv

    2016-07-01

    Purpose To evaluate the ability of dual-energy (DE) computed tomography (CT) to differentiate calcification from acute hemorrhage in the emergency department setting. Materials and Methods In this institutional review board-approved study, all unenhanced DE head CT examinations that were performed in the emergency department in November and December 2014 were retrospectively reviewed. Simulated 120-kVp single-energy CT images were derived from the DE CT acquisition via postprocessing. Patients with at least one focus of intraparenchymal hyperattenuation on single-energy CT images were included, and DE material decomposition postprocessing was performed. Each focal hyperattenuation was analyzed on the basis of the virtual noncalcium and calcium overlay images and classified as calcification or hemorrhage. Sensitivity, specificity, and accuracy were calculated for single-energy and DE CT by using a common reference standard established by relevant prior and follow-up imaging and clinical information. Results Sixty-two cases with 68 distinct intraparenchymal hyperattenuating lesions in which the reference standards were available were included in the study, of which 41 (60%) were confirmed as calcification and 27 (40%) were confirmed as hemorrhage. Sensitivity, specificity, and accuracy of DE CT for the detection of hemorrhage were 96% (95% confidence interval [CI]: 81%, 100%), 100% (95% CI: 91%, 100%), and 99% (95% CI: 92%, 100%) and those of single-energy CT were 74% (95% CI: 54%, 89%), 95% (95% CI: 83%, 99%), and 87% (95% CI: 76%, 94%), respectively. Six of 68 (9%) lesions were classified as indeterminate and three (4%) were misinterpreted with single-energy CT alone and were correctly classified with DE CT. Conclusion DE CT by using material decomposition enables accurate differentiation between calcification and hemorrhage in patients presenting for emergency head imaging and can be especially useful in problem-solving complex cases that are difficult to

  15. A novel method to predict visual field progression more accurately, using intraocular pressure measurements in glaucoma patients.

    PubMed

    2016-01-01

    Visual field (VF) data were retrospectively obtained from 491 eyes in 317 patients with open angle glaucoma who had undergone ten VF tests (Humphrey Field Analyzer, 24-2, SITA standard). First, mean of total deviation values (mTD) in the tenth VF was predicted using standard linear regression of the first five VFs (VF1-5) through to using all nine preceding VFs (VF1-9). Then an 'intraocular pressure (IOP)-integrated VF trend analysis' was carried out by simply using time multiplied by IOP as the independent term in the linear regression model. Prediction errors (absolute prediction error or root mean squared error: RMSE) for predicting mTD and also point wise TD values of the tenth VF were obtained from both approaches. The mTD absolute prediction errors associated with the IOP-integrated VF trend analysis were significantly smaller than those from the standard trend analysis when VF1-6 through to VF1-8 were used (p < 0.05). The point wise RMSEs from the IOP-integrated trend analysis were significantly smaller than those from the standard trend analysis when VF1-5 through to VF1-9 were used (p < 0.05). This was especially the case when IOP was measured more frequently. Thus a significantly more accurate prediction of VF progression is possible using a simple trend analysis that incorporates IOP measurements. PMID:27562553

  16. A novel method to predict visual field progression more accurately, using intraocular pressure measurements in glaucoma patients

    PubMed Central

    Asaoka, Ryo; Fujino, Yuri; Murata, Hiroshi; Miki, Atsuya; Tanito, Masaki; Mizoue, Shiro; Mori, Kazuhiko; Suzuki, Katsuyoshi; Yamashita, Takehiro; Kashiwagi, Kenji; Shoji, Nobuyuki

    2016-01-01

    Visual field (VF) data were retrospectively obtained from 491 eyes in 317 patients with open angle glaucoma who had undergone ten VF tests (Humphrey Field Analyzer, 24-2, SITA standard). First, mean of total deviation values (mTD) in the tenth VF was predicted using standard linear regression of the first five VFs (VF1-5) through to using all nine preceding VFs (VF1-9). Then an ‘intraocular pressure (IOP)-integrated VF trend analysis’ was carried out by simply using time multiplied by IOP as the independent term in the linear regression model. Prediction errors (absolute prediction error or root mean squared error: RMSE) for predicting mTD and also point wise TD values of the tenth VF were obtained from both approaches. The mTD absolute prediction errors associated with the IOP-integrated VF trend analysis were significantly smaller than those from the standard trend analysis when VF1-6 through to VF1-8 were used (p < 0.05). The point wise RMSEs from the IOP-integrated trend analysis were significantly smaller than those from the standard trend analysis when VF1-5 through to VF1-9 were used (p < 0.05). This was especially the case when IOP was measured more frequently. Thus a significantly more accurate prediction of VF progression is possible using a simple trend analysis that incorporates IOP measurements. PMID:27562553

  17. Fecal Calprotectin is an Accurate Tool and Correlated to Seo Index in Prediction of Relapse in Iranian Patients With Ulcerative Colitis

    PubMed Central

    Hosseini, Seyed Vahid; Jafari, Peyman; Taghavi, Seyed Alireza; Safarpour, Ali Reza; Rezaianzadeh, Abbas; Moini, Maryam; Mehrabi, Manoosh

    2015-01-01

    . Besides, FC level of 341 μg/g was identified as the cut-off point with 11.2% and 79.7% relapse rate below and above this point, respectively. Additionally, Pearson correlation coefficient (r) between FC and the Seo index was significant in prediction of relapse (r = 0.63, P < 0.001). Conclusions: As a simple and noninvasive marker, FC is highly accurate and significantly correlated to the Seo activity index in prediction of relapse in the course of quiescent UC in Iranian patients. PMID:25793117

  18. Four novel C20orf54 mutations identified in Brown-Vialetto-Van Laere syndrome patients.

    PubMed

    Dezfouli, Mitra Ansari; Yadegari, Samira; Nafissi, Shahriar; Elahi, Elahe

    2012-09-01

    Brown-Vialetto-Van Laere syndrome (BVVLS) is a very rare neurodegenerative disorder characterized by pontobulbar palsy and sensorineural hearing loss. Its mode of inheritance in affected families has usually been autosomal recessive, although autosomal dominant inheritance and incomplete penetrance have also been reported. Recently, C20orf54 was identified as a causative gene for BVVLS. Twelve different mutations have so far been identified in 10 patients affected with BVVLS or the related disorder Fazio Londe syndrome. Here, results of screening of C20orf54 in three unrelated BVVLS patients are reported. Four novel mutations that affect amino acid changes, p.Asn21Ser, p.Pro220His, p.Ala312Val and p.Gly375Asp, were identified in the patients. The causative nucleotide variations were not observed in 200 control individuals. One of the patients harbored compound heterozygous mutations, but only one mutated allele was observed in each of the two remaining patients. PMID:22718020

  19. The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms.

    PubMed

    Ruiz-González, Agustín; Utrillo, Laia; Bielsa, Silvia; Falguera, Miquel; Porcel, José M

    2016-01-01

    Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82-0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms. PMID:27610265

  20. The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms

    PubMed Central

    Utrillo, Laia; Bielsa, Silvia; Falguera, Miquel; Porcel, José M.

    2016-01-01

    Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p < 0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82–0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms. PMID:27610265

  1. 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…

  2. 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…

  3. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

    PubMed

    Keller, Andreas; Leidinger, Petra; Lange, Julia; Borries, Anne; Schroers, Hannah; Scheffler, Matthias; Lenhof, Hans-Peter; Ruprecht, Klemens; Meese, Eckart

    2009-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS. PMID:19823682

  4. Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls

    PubMed Central

    Lange, Julia; Borries, Anne; Schroers, Hannah; Scheffler, Matthias; Lenhof, Hans-Peter; Ruprecht, Klemens; Meese, Eckart

    2009-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS. PMID:19823682

  5. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    PubMed Central

    Hillman, R. Tyler; Ward, Kristy; Saenz, Cheryl; McHale, Michael; Plaxe, Steven

    2015-01-01

    Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials. PMID:26011384

  6. Mean Polyp per Patient Is an Accurate and Readily Obtainable Surrogate for Adenoma Detection Rate: Results from an Opportunistic Screening Colonoscopy Program

    PubMed Central

    Delavari, Alireza; Salimzadeh, Hamideh; Bishehsari, Faraz; Sobh Rakhshankhah, Elham; Delavari, Farnaz; Moossavi, Shirin; Khosravi, Pejman; Nasseri-Moghaddam, Siavosh; Merat, Shahin; Ansari, Reza; Vahedi, Homayoon; Shahbazkhani, Bijan; Saberifiroozi, Mehdi; Sotoudeh, Masoud; Malekzadeh, Reza

    2015-01-01

    BACKGROUND The incidence of colorectal cancer is rising in several developing countries. In the absence of integrated endoscopy and pathology databases, adenoma detection rate (ADR), as a validated quality indicator of screening colonoscopy, is generally difficult to obtain in practice. We aimed to measure the correlation of polyp-related indicators with ADR in order to identify the most accurate surrogate(s) of ADR in routine practice. METHODS We retrospectively reviewed the endoscopic and histopathological findings of patients who underwent colonoscopy at a tertiary gastrointestinal clinic. The overall ADR and advanced-ADR were calculated using patient-level data. The Pearson’s correlation coefficient (r) was applied to measure the strength of the correlation between the quality metrics obtained by endoscopists. RESULTS A total of 713 asymptomatic adults aged 50 and older who underwent their first-time screening colonoscopy were included in this study. The ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed good correlations between polyp detection rate (PDR) and ADR (r=0.93), and mean number of polyp per patient (MPP) and ADR (r=0.88) throughout the colon. There was a positive, yet insignificant correlation between advanced ADRs and non-advanced ADRs (r=0.42, p=0.35). CONCLUSION MPP is strongly correlated with ADR, and can be considered as a reliable and readily obtainable proxy for ADR in opportunistic screening colonoscopy programs. PMID:26609349

  7. A Case Of Invasive Aspergillosis in a Patient with No Identifiable Immunodeficiencies

    PubMed Central

    Siddiqui, K; Douglas, M; Carey, MP; Benamer, HTS

    2008-01-01

    Invasive fungal infections usually affect patients with immunodeficiencies and very rarely patients with no known or identifiable risk factors. Diagnosis could be delayed in patients without previously known immunodeficiencies due to a low index of suspicion, leading to a delay in treatment and a potential poor outcome. We report a case of a postpartum woman with no history of immuno-compromised disease who developed left hemiparesis with evidence of invasive aspergollosis affecting the nervous system, and leading to fatal outcome. The patient had a mass-like lesion in the neuroimaging with soft tissue shadowing in the chest x-ray leading to initial diagnosis of tuberculosis. The brain biopsy showed changes consistent with a diagnosis of aspergillosis. The source of the aspergillus infection was not clear. Aspergillus infection should be considered in patients with no identifiable immunodeficiencies who have abnormal brain imaging and chest x-ray, as early treatment may alter the outcome. PMID:21516164

  8. 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

  9. Geriatric forensics: A dentist's perspective and contribution to identify existence of elder abuse among his patients

    PubMed Central

    Mattoo, Khurshid A; Shalabh, Kumar; Khan, Aamir

    2010-01-01

    Aims and Objectives: To identify existence of elder abuse among the patients seeking prosthetic rehabilitation of missing teeth. Materials and Methods: This study was conducted on 300 patients aged 65 years and above. It included 238 males and 62 females. A questionnaire prepared by a psychologist was used to evaluate the patient in various aspects of neglect. Results: The results revealed that 40% of the total subjects that were studied were suffering from neglect in one way or the other. Conclusion: The results conclude that elder negligence was highly prevalent in elder patients who report to the dental office seeking oral prosthetic rehabilitation. PMID:21731345

  10. 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

  11. 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. PMID:16602686

  12. Molecular Testing of 163 Patients with Morquio A (Mucopolysaccharidosis IVA) Identifies 39 Novel GALNS Mutations

    PubMed Central

    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.; Riberio, I.; Wang, R.Y.; Miller, N.

    2014-01-01

    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 produce protein with 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. PMID:24726177

  13. Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing.

    PubMed

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

    2016-05-01

    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

  14. Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System

    PubMed Central

    Staropoli, John F.; Haliw, Larissa; Biswas, Sunita; Garrett, Lillian; Hölter, Sabine M.; Becker, Lore; Skosyrski, Sergej; Da Silva-Buttkus, Patricia; Calzada-Wack, Julia; Neff, Frauke; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adler, Thure; Puk, Oliver; Sun, Minxuan; Favor, Jack; Racz, Ildikó; Bekeredjian, Raffi; Busch, Dirk H.; Graw, Jochen; Klingenspor, Martin; Klopstock, Thomas; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Lopez, Edith; Harati, Hayat; Hill, Eric; Krause, Daniela S.; Guide, Jolene; Dragileva, Ella; Gale, Evan; Wheeler, Vanessa C.; Boustany, Rose-Mary; Brown, Diane E.; Breton, Sylvie; Ruether, Klaus; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Cotman, Susan L.

    2012-01-01

    Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development. PMID:22701626

  15. [The death dates of Seishu Hanaoka's patients with breast cancer: a report of newly identified three patients].

    PubMed

    Matsuki, Akitomo

    2002-06-01

    Among 155 patients with breast cancer treated by Seishu Hanaoka the exact death dates of only five patients including Kan Aiya, the first to have received a tumour excision under general anesthesia are known to us and the remaining 149 patients remain unclarified concerning their death dates. The reason is mainly due to a fact that the descriptions of "Nyugan Seimei Roku" (A Name List of Breast Cancer Patients) are inaccurate. According to recent field survey on the burial records of several temples which have been described in the "Nyugan Seimei Roku," the author could clarify the death dates of two patients. The one is the wife of Kohfuku-ji Temple's priest who died on Feb 20, 1813, and the other in the wife of Honko-ji Temple's priest, died on July 8, 1834. Both survived 1 year 4 months, and 1 year 3 months, postoperatively. One more patient's death date is identified by chance. Consequently, the death dates of eight patients among 155 have been identified so far. PMID:12398071

  16. 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.

  17. Institutional decision-making to select patient care devices: identifying venues to promote patient safety.

    PubMed

    Keselman, Alla; Patel, Vimla L; Johnson, Todd R; Zhang, Jiajie

    2003-01-01

    Many medical errors that involve drug infusion devices are related to classic interface problems. Although manufacturers are becoming increasingly aware of human factors design considerations, many devices that are currently on the market are still sub-optimal for human use. This places significant responsibility for device selection on institutional purchasing groups. Theories of naturalistic decision-making point to many potential strengths and pitfalls of group decision-making processes that may affect the final outcome. This paper describes a retrospective analysis of decision-making process for infusion pump selection in a large hospital and focuses on factors related to patient safety. Through a series of detailed interviews and a study of relevant documentation we characterized the nature of the decision-making, patterns of communication, and the roles of different participants. Findings show that although the process involves a number of different professional groups and committees, the information flow among them is restricted. This results in inadequate representation of critical device usability considerations in the decision-making process. While all participants view device safety as an important consideration in the selection process, administrators (who are the final decision-makers) tend to equate safety with technical accuracy and reliability, paying less attention to the role of human factors in safe device use. Findings suggest that collaborative communication technology and automated evidence-based guidelines could provide support to institutional decision-making, ensuring that the process is efficient, effective, and ultimately safe for the patients. PMID:14552845

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

    PubMed Central

    Khaled, Yazan S.; Ammori, Basil J.; Elkord, Eyad

    2016-01-01

    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. PMID:26885615

  19. Applying Classification Trees to Hospital Administrative Data to Identify Patients with Lower Gastrointestinal Bleeding

    PubMed Central

    Siddique, Juned; Ruhnke, Gregory W.; Flores, Andrea; Prochaska, Micah T.; Paesch, Elizabeth; Meltzer, David O.; Whelan, Chad T.

    2015-01-01

    Background Lower gastrointestinal bleeding (LGIB) is a common cause of acute hospitalization. Currently, there is no accepted standard for identifying patients with LGIB in hospital administrative data. The objective of this study was to develop and validate a set of classification algorithms that use hospital administrative data to identify LGIB. Methods Our sample consists of patients admitted between July 1, 2001 and June 30, 2003 (derivation cohort) and July 1, 2003 and June 30, 2005 (validation cohort) to the general medicine inpatient service of the University of Chicago Hospital, a large urban academic medical center. Confirmed cases of LGIB in both cohorts were determined by reviewing the charts of those patients who had at least 1 of 36 principal or secondary International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9-CM) diagnosis codes associated with LGIB. Classification trees were used on the data of the derivation cohort to develop a set of decision rules for identifying patients with LGIB. These rules were then applied to the validation cohort to assess their performance. Results Three classification algorithms were identified and validated: a high specificity rule with 80.1% sensitivity and 95.8% specificity, a rule that balances sensitivity and specificity (87.8% sensitivity, 90.9% specificity), and a high sensitivity rule with 100% sensitivity and 91.0% specificity. Conclusion These classification algorithms can be used in future studies to evaluate resource utilization and assess outcomes associated with LGIB without the use of chart review. PMID:26406318

  20. Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.

    PubMed

    Tort, Frederic; García-Silva, María Teresa; Ferrer-Cortès, Xènia; Navarro-Sastre, Aleix; Garcia-Villoria, Judith; Coll, Maria Josep; Vidal, Enrique; Jiménez-Almazán, Jorge; Dopazo, Joaquín; Briones, Paz; Elpeleg, Orly; Ribes, Antonia

    2013-01-01

    3-Methylglutaconic aciduria (3-MGA-uria) is a heterogeneous group of syndromes characterized by an increased excretion of 3-methylglutaconic and 3-methylglutaric acids. Five types of 3-MGA-uria (I to V) with different clinical presentations have been described. Causative mutations in TAZ, OPA3, DNAJC19, ATP12, ATP5E, and TMEM70 have been identified. After excluding the known genetic causes of 3-MGA-uria we used exome sequencing to investigate a patient with Leigh syndrome and 3-MGA-uria. We identified a homozygous variant in SERAC1 (c.202C>T; p.Arg68*), that generates a premature stop codon at position 68 of SERAC1 protein. Western blot analysis in patient's fibroblasts showed a complete absence of SERAC1 that was consistent with the prediction of a truncated protein and supports the pathogenic role of the mutation. During the course of this project a parallel study identified mutations in SERAC1 as the genetic cause of the disease in 15 patients with MEGDEL syndrome, which was compatible with the clinical and biochemical phenotypes of the patient described here. In addition, our patient developed microcephaly and optic atrophy, two features not previously reported in MEGDEL syndrome. We highlight the usefulness of exome sequencing to reveal the genetic bases of human rare diseases even if only one affected individual is available. PMID:23707711

  1. Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness

    PubMed Central

    French, Christi L.; Ye, Fei; Revetta, Frank; Zhang, Bing; Coffey, Robert J.; Washington, M. Kay; Deane, Natasha G.; Beauchamp, R. Daniel; Weaver, Alissa M.

    2015-01-01

    A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2) were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3) was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness. PMID:26097693

  2. 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

  3. Use of Augmented Meaningful Use Criteria to Identify Patients Eligible for Lung Cancer Screening

    PubMed Central

    Raz, Dan J.; Dunham, Rachel; Tiep, Brian; Sandoval, Argelia; Grannis, Frederic; Rotter, Arnold; Kim, Jae Y.

    2015-01-01

    Background Lung cancer screening (LCS) with low dose radiation computed tomography saves lives. Despite recent US Preventative Services Task Force draft endorsement of LCS, a minority of patients eligible is screened. Meaningful use is a set of standards for Electronic Health Records (EHR) established by the Centers for Medicare and Medicaid Services and includes reporting of smoking status. We sought to improve rates of LCS among patients treated at our institution by identifying eligible patients using augmented smoking-related meaningful use criteria. Methods We launched a LCS program at our institution, an NCCN cancer center, in January 2013. We developed a “Tobacco Screen”, administered by clinic staff to all adult outpatients every 6 months and entered into the EHR. This contained smoking-related meaningful use criteria, as well as a pack-year calculation and quit date, if applicable. Weekly electronic reports of patients who met eligibility criteria for LCS were generated, and EHR review excluded patients who had a chest CT within 12 months or who were undergoing cancer treatment. We then contacted those patients to review eligibility for LCS and communicated with the primary treating physician regarding the plan for LCS. Results During the first 3 months of the program, 4 patients were enrolled, 2 by physician-referral and 2 by self-referral. We then began to utilize the Tobacco Screen reports and identified 418 patients potentially eligible for LCS. Over the next 7 months, we enrolled a total of 110 patients. 58 (53%) were identified from the Tobacco Screen, 32 (29%) were self-referred, and 20 (18%) were physician referrals. Three stage I lung cancers were detected and treated. The tobacco screen was easily implemented by clinic staff and took a median time of 2 minutes to enter for current and former smokers. Lack of response to attempts at telephone contact and objection to paying out-of-pocket costs were the most common reasons for failing to screen

  4. 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

  5. The use of fiber tractography for identifying patients with Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Dong, Kyung-Rae; Goo, Eun-Hoe; Lee, Jae-Seung; Chung, Woon-Kwan

    2013-01-01

    This study examined the usefulness of fiber tractography (FT) for identifying patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) through diffusion tensor imaging (DTI). DTI was performed on twelve patients with AD (four males and eight females, mean age: 78.1 ± 7.5 years) and an eleven patients with MCI (five males and six females, mean age: 69.3 ± 8.0 years) from January to December 2011 by using a 3.0T scanner. Two regions of interest were drawn on the pyramidal tract of Pons and the posterior limb of the internal capsule, which passed through both cortico spinal tracts on the color-cored fractional anisotropy (FA) map. The numbers of white matter fibers on the DTIs in the patients with AD and MCI were determined. The numbers of white matter fibers in the AD patients were 1055.67 ± 333.12 and 860.75 ± 355.50 on the left and the right, respectively. In the patients with MCI, the numbers of white matter fibers and were 1329.82 ± 238.99 and 1316.55 ± 215.25 on the left and the right, respectively. The difference between the right and the left sides in the AD patients was slightly higher than that in the MCI patients.

  6. Identifying key domains of health-related quality of life for patients with Chronic Obstructive Pulmonary Disease: the patient perspective

    PubMed Central

    2014-01-01

    Background Numerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning. Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population. The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective. Methods Twenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them. During the interview, the patients were asked to indicate in which way the selected domains impact their lives. Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes. Results The most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD. Conclusion We identified which domains of HRQoL are most important to patients with COPD. One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD. PMID:25005552

  7. Vessel Architectural Imaging Identifies Cancer Patient Responders to Anti-angiogenic Therapy

    PubMed Central

    Emblem, Kyrre E.; Mouridsen, Kim; Bjornerud, Atle; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Wen, Patrick Y.; Ivy, Percy; Batchelor, Tracy T.; Rosen, Bruce R.; Jain, Rakesh K.; Sorensen, A. Gregory

    2013-01-01

    Measurement of vessel caliber by Magnetic Resonance Imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI coined as Vessel Architectural Imaging (VAI) that exploits an intriguing and overlooked temporal shift in the MR signal forming the basis for vessel caliber estimation and show how this phenomenon can reveal new information on vessel type and function not assessed by any other non-invasive imaging technique. We also show how this biomarker can provide novel biological insights into the treatment of cancer patients. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation levels and reduce vessel calibers in patients with recurrent glioblastomas, and more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies. PMID:23955713

  8. Assessing Student Pharmacists’ Ability to Identify Drug-Related Problems in Patients Within a Patient-Centered Medical Home

    PubMed Central

    Bulkley, Christina F.; Truong, Teresa; Carter, Sandra M.

    2014-01-01

    Objective. To quantify, describe, and categorize patient drug-related problems (DRPs) and recommendations identified by fourth-year (P4) student pharmacists during a live medication reconciliation activity within a patient-centered medical home (PCMH). Methods. Fourth-year student pharmacists conducted chart reviews, identified and documented DRPs, obtained live medication histories, and immediately provided findings and recommendations to the attending physicians. Documentation of DRPs and recommendations were analyzed retrospectively. Results. Thirty-eight students completed 99 medication reconciliation sessions from June 2011 to October 2012 during their advanced pharmacy practice experience (APPE). The students obtained 676 patient medication histories and identified or intervened on 1308 DRPs. The most common DRPs reported were incomplete medication list and diagnostic/laboratory testing needed. Physicians accepted 1,018 (approximately 78%) recommendations. Conclusion. Student pharmacists successfully identified and reduced DRPs through a live medication reconciliation process within an academic-based PCMH model. Their medication history-taking skills improved and medication use was optimized. PMID:24558274

  9. 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

  10. Exploring methods for identifying related patient safety events using structured and unstructured data.

    PubMed

    Fong, Allan; Hettinger, A Zachary; Ratwani, Raj M

    2015-12-01

    Most healthcare systems have implemented patient safety event reporting systems to identify safety hazards. Searching the safety event data to find related patient safety reports and identify trends is challenging given the complexity and quantity of these reports. Structured data elements selected by the event reporter may be inaccurate and the free-text narrative descriptions are difficult to analyze. In this paper we present and explore methods for utilizing both the unstructured free-text and structured data elements in safety event reports to identify and rank similar events. We evaluate the results of three different free-text search methods, including a unique topic modeling adaptation, and structured element weights, using a patient fall use case. The various search techniques and weight combinations tended to prioritize different aspects of the event reports leading to different search and ranking results. These search and prioritization methods have the potential to greatly improve patient safety officers, and other healthcare workers, understanding of which safety event reports are related. PMID:26432354

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

    PubMed

    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

  12. 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

  13. Clustering analysis to identify distinct spectral components of encephalogram burst suppression in critically ill patients.

    PubMed

    Zhou, David W; Westover, M Brandon; McClain, Lauren M; Nagaraj, Sunil B; Bajwa, Ednan K; Quraishi, Sadeq A; Akeju, Oluwaseun; Cobb, J Perren; Purdon, Patrick L

    2015-01-01

    Millions of patients are admitted each year to intensive care units (ICUs) in the United States. A significant fraction of ICU survivors develop life-long cognitive impairment, incurring tremendous financial and societal costs. Delirium, a state of impaired awareness, attention and cognition that frequently develops during ICU care, is a major risk factor for post-ICU cognitive impairment. Recent studies suggest that patients experiencing electroencephalogram (EEG) burst suppression have higher rates of mortality and are more likely to develop delirium than patients who do not experience burst suppression. Burst suppression is typically associated with coma and deep levels of anesthesia or hypothermia, and is defined clinically as an alternating pattern of high-amplitude "burst" periods interrupted by sustained low-amplitude "suppression" periods. Here we describe a clustering method to analyze EEG spectra during burst and suppression periods. We used this method to identify a set of distinct spectral patterns in the EEG during burst and suppression periods in critically ill patients. These patterns correlate with level of patient sedation, quantified in terms of sedative infusion rates and clinical sedation scores. This analysis suggests that EEG burst suppression in critically ill patients may not be a single state, but instead may reflect a plurality of states whose specific dynamics relate to a patient's underlying brain function. PMID:26737967

  14. 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

  15. A novel integrative approach to identify lncRNAs associated with the survival of melanoma patients.

    PubMed

    Guo, Linna; Yao, Lijie; Jiang, Yang

    2016-07-10

    Long non-coding RNAs (lncRNAs) play important roles in diagnosis and prognosis of human cancers. With the development of microarray and RNA-seq, gene expression were measured in more and more tumor types for identification of prognostic markers. However, lncRNA expression profiles of tumor patients with follow-up information were rare. In this study, we developed a novel simple computational approach, which didn't use lncRNA expression, to identify lncRNAs associated with the survival of melanoma patients through integrating gene expression and lncRNA-target networks. First, we calculated the significance of associations between gene expression and patients' survival. Second, we constructed the experimentally validated lncRNA-target gene networks. Next, the significance of lncRNAs were obtained by combination of the p-values of their neighbor genes. Finally, we identified 15 lncRNAs that were significantly associated with the survival of melanoma patients (p<0.05), which were supported by functional analysis and literature review. Collectively, this study provides an effective approach to predict the lncRNA signatures for outcomes of tumor patients without lncRNA expression profiles. PMID:27016304

  16. Preparing patients to travel abroad safely. Part 1: Taking a travel history and identifying special risks.

    PubMed Central

    Thomas, R. E.

    2000-01-01

    OBJECTIVE: To present for family physicians without access to a travel clinic and the Internet the questions to ask about the medical history and itinerary of their patients traveling abroad. To suggest ways to identify and advise high-risk patients. QUALITY OF EVIDENCE: MEDLINE searches from 1990 to November 1998 located 51 articles on travel and diabetes, 37 on travel and chronic obstructive pulmonary disease (COPD), 63 on travel and heart disease, 192 on travel and pregnancy, and 298 on travel with infants or children. Additional searches were undertaken in September 1999. The quality of evidence in most articles is level III (expert opinion). There are no randomized controlled trials of the best advice for family physicians to give travelers. MAIN MESSAGE: A history should include countries to be visited, planned activities, previous tropical travel, medical history, vaccination status, whether children are traveling, pregnancy status, and patients' opinions of the risks and precautions needed. Detailed advice should be given to reduce risks. The main causes of mortality abroad are existing cardiovascular conditions and accidents. High-risk conditions to be identified in travelers are cardiovascular illness, COPD, diabetes, immunodeficiency, pregnancy, and traveling with children. CONCLUSIONS: Patients with cardiovascular illness or COPD should be advised to avoid too much exertion while traveling. Detailed instruction should be given to diabetic patients on how to maintain stable glucose levels, to pregnant women on avoiding malarial infection, and to parents on protecting their children from infections and accidents. PMID:10660795

  17. Challenges in Identifying the Foot Motor Region in Patients with Brain Tumor on Routine MRI: Advantages of fMRI

    PubMed Central

    Fisicaro, R.A.; Jiao, R.X.; Stathopoulos, C.; Brennan, N.M. Petrovich; Peck, K.K.; Holodny, A.I.

    2016-01-01

    BACKGROUND AND PURPOSE Accurate localization of the foot/leg motor homunculus is essential because iatrogenic damage can render a patient wheelchair- or bed-bound. We hypothesized the following: 1) Readers would identify the foot motor homunculus <100% of the time on routine MR imaging, 2) neuroradiologists would perform better than nonradiologists, and 3) those with fMRI experience would perform better than those without it. MATERIALSANDMETHODS Thirty-five attending-level raters (24 neuroradiologists, 11 nonradiologists) evaluated 14 brain tumors involving the frontoparietal convexity. Raters were asked to identify the location of the foot motor homunculus and determine whether the tumor involved the foot motor area and/or motor cortex by using anatomic MR imaging. Results were compared on the basis of prior fMRI experience and medical specialty by using Mann-Whitney U test statistics. RESULTS No rater was 100% correct. Raters correctly identified whether the tumor was in the foot motor cortex 77% of the time. Raters with fMRI experience were significantly better than raters without experience at foot motor fMRI centroid predictions (13 ± 6 mm versus 20 ± 13 mm from the foot motor cortex center, P = 2 × 10−6) and arrow placement in the motor gyrus (67% versus 47%, P = 7 × 10−5). Neuroradiologists were significantly better than nonradiologists at foot motor fMRI centroid predictions (15 ± 8 mm versus 20 ± 14 mm, P = .005) and arrow placement in the motor gyrus (61% versus 46%, P = .008). CONCLUSIONS The inability of experienced readers to consistently identify the location of the foot motor homunculus on routine MR imaging argues for using fMRI in the preoperative setting. Experience with fMRI leads to improved accuracy in identifying anatomic structures, even on routine MR imaging. PMID:25882288

  18. 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. PMID:24296270

  19. Number of Gastrointestinal Symptoms is a Useful Means of Identifying Patients with Cancer for Dysphagia.

    PubMed

    Tsukamoto, Machi; Manabe, Noriaki; Kamada, Tomoari; Hirai, Toshihiro; Hata, Jiro; Haruma, Ken; Inoue, Kazuhiko

    2016-08-01

    Dysphagia is a symptom suggestive of severe underlying pathology, although its causes include organic and non-organic disorders. The epidemiology of dysphagia is, however, poorly understood. We evaluated the prevalence of dysphagia in outpatients in Japan, measured the proportion ultimately found to have an organic cause, and recorded the nature of their symptoms and the underlying disorder. Of 5362 consecutive outpatients attending the Digestive Center at our hospital between June 1, 2010 and December 31, 2012, 186 patients (3.5 %) had dysphagia with a frequency score of ≥5 out of 6. The most common diagnosis was cancer (34 patients, 18.3 %), followed by gastroesophageal reflux disease (24 patients, 12.9 %). An esophageal motility disorder was diagnosed in 21 patients (11.3 %); the causes in the remaining 107 patients (57.5 %) were miscellaneous. Multivariable analysis identified the following predictors of cancer: age ≥ 54 years, weight loss, being a drinker of alcohol, and ≤2 gastrointestinal symptoms. Our findings can be used to inform the prioritization of referrals from primary care for investigation and treatment for patients with cancer for dysphagia. PMID:27115760

  20. Clustering analysis to identify distinct spectral components of encephalogram burst suppression in critically ill patients

    PubMed Central

    Zhou, David W.; Westover, M. Brandon; McClain, Lauren M.; Nagaraj, Sunil B.; Bajwa, Ednan K.; Quraishi, Sadeq A.; Akeju, Oluwaseun; Cobb, J. Perren; Purdon, Patrick L.

    2016-01-01

    Millions of patients are admitted each year to intensive care units (ICUs) in the United States. A significant fraction of ICU survivors develop life-long cognitive impairment, incurring tremendous financial and societal costs. Delirium, a state of impaired awareness, attention and cognition that frequently develops during ICU care, is a major risk factor for post-ICU cognitive impairment. Recent studies suggest that patients experiencing electroencephalogram (EEG) burst suppression have higher rates of mortality and are more likely to develop delirium than patients who do not experience burst suppression. Burst suppression is typically associated with coma and deep levels of anesthesia or hypothermia, and is defined clinically as an alternating pattern of high-amplitude “burst” periods interrupted by sustained low-amplitude “suppression” periods. Here we describe a clustering method to analyze EEG spectra during burst and suppression periods. We used this method to identify a set of distinct spectral patterns in the EEG during burst and suppression periods in critically ill patients. These patterns correlate with level of patient sedation, quantified in terms of sedative infusion rates and clinical sedation scores. This analysis suggests that EEG burst suppression in critically ill patients may not be a single state, but instead may reflect a plurality of states whose specific dynamics relate to a patient’s underlying brain function. PMID:26737967

  1. Identifying illness perception schemata and their association with depression and quality of life in cardiac patients.

    PubMed

    Le Grande, Michael R; Elliott, Peter C; Worcester, Marian U C; Murphy, Barbara M; Goble, Alan J; Kugathasan, Vanessa; Sinha, Karan

    2012-01-01

    The purpose of this paper is to identify groups of cardiac patients who share similar perceptions about their illness and to examine the relationships between these schemata and psychosocial outcomes such as quality of life and depression. A total of 190 cardiac patients with diagnoses of myocardial infarction, stable angina pectoris or chronic heart failure, completed a battery of psychosocial questionnaires within four weeks of their admission to hospital. These included the Brief Illness Perceptions Questionnaire (BIPQ), Beck Depression Inventory II (BDI II) and The MacNew Health-related Quality of Life instrument (MacNew). BIPQ items were subjected to latent class analysis (LCA) and the resulting groups were compared according to their BDI II and MacNew scores. LCA identified a five-class model of illness perception which comprised the following: (1) Consequence focused and mild emotional impact, n = 55, 29%; (2) Low illness perceptions and low emotional impact, n = 45, 24%; (3) Control focused and mild emotional impact, n = 10, 5%; (4) Consequence focused and high emotional impact, n = 60, 32%; and (5) Consequence focused and severe emotional impact, n = 20, 10%. Gender and diagnosis did not appear to reflect class membership except that class 2 had a significantly higher proportion of AMI patients than did class 5. There were numerous significant differences between classes in regards to depression and health-related quality of life. Notably, classes 4 and 5 are distinguished by relatively high BDI II scores and low MacNew scores. Identifying classes of cardiac patients based on their illness perception schemata, in hospital or shortly afterwards, may identify those at risk of developing depressive symptoms and poor quality of life. PMID:22416847

  2. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis.

    PubMed

    Spier, Isabel; Kerick, Martin; Drichel, Dmitriy; Horpaopan, Sukanya; Altmüller, Janine; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Adam, Ronja; Zhao, Bixiao; Becker, Tim; Lifton, Richard P; Holinski-Feder, Elke; Perner, Sven; Thiele, Holger; Nöthen, Markus M; Hoffmann, Per; Timmermann, Bernd; Schweiger, Michal R; Aretz, Stefan

    2016-04-01

    In up to 30% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or tumor suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated patients. All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes (DSC2, PIEZO1, ZSWIM7). In the validation cohort, further variants predicted to be pathogenic were identified in DSC2 and PIEZO1. According to the somatic mutation spectra, the adenomas in this patient cohort follow the classical pathways of colorectal tumorigenesis. The present study identified three candidate genes which might represent rare causes for a predisposition to colorectal adenoma formation. Especially PIEZO1 (FAM38A) and ZSWIM7 (SWS1) warrant further exploration. To evaluate the clinical relevance of these genes, investigation of larger patient cohorts and functional studies are required. PMID:26780541

  3. Identifying patients with hypertension: a case for auditing electronic health record data.

    PubMed

    Baus, Adam; Hendryx, Michael; Pollard, Cecil

    2012-01-01

    Problems in the structure, consistency, and completeness of electronic health record data are barriers to outcomes research, quality improvement, and practice redesign. This nonexperimental retrospective study examines the utility of importing de-identified electronic health record data into an external system to identify patients with and at risk for essential hypertension. We find a statistically significant increase in cases based on combined use of diagnostic and free-text coding (mean = 1,256.1, 95% CI 1,232.3-1,279.7) compared to diagnostic coding alone (mean = 1,174.5, 95% CI 1,150.5-1,198.3). While it is not surprising that significantly more patients are identified when broadening search criteria, the implications are critical for quality of care, the movement toward the National Committee for Quality Assurance's Patient-Centered Medical Home program, and meaningful use of electronic health records. Further, we find a statistically significant increase in potential cases based on the last two or more blood pressure readings greater than or equal to 140/90 mm Hg (mean = 1,353.9, 95% CI 1,329.9-1,377.9). PMID:22737097

  4. Identifying Patients with Hypertension: A Case for Auditing Electronic Health Record Data

    PubMed Central

    Baus, Adam; Hendryx, Michael; Pollard, Cecil

    2012-01-01

    Problems in the structure, consistency, and completeness of electronic health record data are barriers to outcomes research, quality improvement, and practice redesign. This nonexperimental retrospective study examines the utility of importing de-identified electronic health record data into an external system to identify patients with and at risk for essential hypertension. We find a statistically significant increase in cases based on combined use of diagnostic and free-text coding (mean = 1,256.1, 95% CI 1,232.3–1,279.7) compared to diagnostic coding alone (mean = 1,174.5, 95% CI 1,150.5—1,198.3). While it is not surprising that significantly more patients are identified when broadening search criteria, the implications are critical for quality of care, the movement toward the National Committee for Quality Assurance's Patient-Centered Medical Home program, and meaningful use of electronic health records. Further, we find a statistically significant increase in potential cases based on the last two or more blood pressure readings greater than or equal to 140/90 mm Hg (mean = 1,353.9, 95% CI 1,329.9—1,377.9). PMID:22737097

  5. Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome.

    PubMed

    Hino-Fukuyo, Naomi; Kikuchi, Atsuo; Arai-Ichinoi, Natsuko; Niihori, Tetsuya; Sato, Ryo; Suzuki, Tasuku; Kudo, Hiroki; Sato, Yuko; Nakayama, Tojo; Kakisaka, Yosuke; Kubota, Yuki; Kobayashi, Tomoko; Funayama, Ryo; Nakayama, Keiko; Uematsu, Mitsugu; Aoki, Yoko; Haginoya, Kazuhiro; Kure, Shigeo

    2015-06-01

    West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50% of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22%, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36%, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21%, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14%, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome. PMID:25877686

  6. Raman spectroscopy of endoscopic colonic biopsies from patients with ulcerative colitis to identify mucosal inflammation and healing

    PubMed Central

    Addis, James; Mohammed, Noor; Rotimi, Olorunda; Magee, Derek; Jha, Animesh; Subramanian, Venkataraman

    2016-01-01

    Raman spectroscopy was used to differentiate between mucosally healed (or quiescent) and inflamed colon tissue, as assessed endoscopically, in patients with ulcerative colitis. From the analysis of the Raman spectra of 60 biopsy tissue samples, clear differences were identified between the spectra of the quiescent and inflamed tissue. Three carotenoid peaks were found to be approximately twice as intense in the inflamed tissue. Two phospholipid peaks were found to be significantly lower in the inflamed tissue. Using multivariate statistical analysis, we show that these five peaks can be used to discriminate between endoscopically quiescent and inflamed tissue. We also correlated the Raman data with a histological assessment of the tissue. Four of the five peaks were found to be significantly different between the spectra of histologically healed (or quiescent) and histologically inflamed tissue. These findings indicate the ability of Raman spectroscopy to accurately classify colon tissue as either quiescent or inflamed, irrespective of whether an endoscopic or histological grading scheme is followed. We thus demonstrate that Raman spectroscopy could potentially be used as an early diagnosis tool for assessing the presence of mucosal healing or inflammation in patients with ulcerative colitis. PMID:27231640

  7. 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

  8. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma

    PubMed Central

    Byrum, Stephanie D.; Larson, Signe K.; Avaritt, Nathan L.; Moreland, Linley E.; Mackintosh, Samuel G.; Cheung, Wang L.; Tackett, Alan J.

    2013-01-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression. PMID:23976835

  9. Occult sternal metastasis identified by laminography in patients with chest pain.

    PubMed

    LaBan, M M; Newman, J M

    1984-04-01

    Six patients with occult sternal metastasis presenting with chest pain, and four with sternal deformity associated with "arthritis" had undergone routine roentgenographic examinations, reported as "normal." Subsequent laminography of the sternum demonstrated lytic lesions confirmed by needle biopsy. Adenocarcinoma of the lung and breast were identified in two each of four patients; myeloma and kidney neoplasms were the primary source of malignancy in the remaining two patients. In widespread malignancy, metastasis to the skeletal chest wall is a well-recognized occurrence. Infrequently, it can be an isolated manifestation of an occult or recurrent malignancy, initially overlooked when routine roentgenograms are read as normal. Although sternal x-rays remain the most important means of diagnosis, in suspected cases of sternal metastasis laminography alone may initially reveal lytic lesions. PMID:6712441

  10. Inflammatory molecules expression pattern for identifying pathogen species in febrile patient serum

    PubMed Central

    LIU, KUAN-TING; LIU, YAO-HUA; LIN, CHUN-YU; KUO, PO-LIN; YEN, MENG-CHI

    2016-01-01

    Inflammatory molecules, such as cytokines and chemokines, have been considered markers for bacterial or viral infection in serum of patients in numerous studies. The aim of the present study was to investigate whether we were able to identify the pathogen species through patterns of inflammatory molecules. A total of 132 patients with elevated body temperature (tympanic temperature, >38.3°C) were recruited for this study. The concentrations of various inflammatory molecules in the patients' serum were evaluated using a cytometric bead array. Higher concentrations of interleukin (IL)-6 and IL-8 were detected in bacterial infection groups (patients with positive and negative blood cultures), as compared with the viral infection group. Viral infection (including influenza and dengue viral infections) was associated with higher concentrations of interferon-γ-inducible protein 10 (IP-10), as compared with the bacterial infection group. In addition, IL-8 levels in the gram-negative bacteria group were higher, as compared with the gram-positive bacteria group. However, IL-8 was insufficient for bacterial species identification. By contrast, dengue virus infection induced the highest serum level of IP-10 among all groups. In conclusion, detection of the patterns of inflammatory molecules may aid the subsequent management and treatment modalities in hospitals, although evaluation of these molecules alone may be insufficient for identifying the pathogen species. PMID:27347055

  11. 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

  12. Identifying the educational needs and concerns of newly diagnosed patients with breast cancer after surgery.

    PubMed

    Stephens, Patrice A; Osowski, Maryjo; Fidale, Mary Sue; Spagnoli, Cathy

    2008-04-01

    Many factors may interfere with the ability of women newly diagnosed with breast cancer to cope with treatment. Nurses should be aware of patients' needs during this critical time. The purpose of this study was to identify the educational needs and concerns of newly diagnosed patients with breast cancer after surgery. A phone interview with patients was conducted approximately one week after breast cancer surgery. A convenience sample of 200 patients was recruited from four hospitals within a large midwestern healthcare system. The subjects were interviewed by breast health specialists and navigators involved in their education and support and were asked to participate in a short interview during a surgical follow-up phone call. Study results indicate that fear of recurrence and anxiety regarding postoperative treatments accounted for more than 65% of the responses to the question "What concerns you most about your new diagnosis?" Emotional, social, and physical limitations were identified as most important in dealing with a breast cancer diagnosis. As breast health specialists and navigators, nurses can improve the quality of care for women with breast cancer and their families by providing additional support services and post-treatment information during the initial education and follow-up call. PMID:18390461

  13. 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

  14. Use of nasometry as a diagnostic tool for identifying patients with velopharyngeal impairment.

    PubMed

    Dalston, R M; Warren, D W; Dalston, E T

    1991-04-01

    A series of 117 patients were studied in an attempt to determine the extent to which acoustic assessments of speech made with a Kay Elemetrics Nasometer corresponded with aerodynamic estimates of velopharyngeal area and clinical judgments of hypernasality. Nasometer data were obtained while patients read or repeated a standardized passage with no nasal consonants. Pressure-flow data were obtained from 96 of these patients during repeated productions of the word "papa." Listener judgments were made in a clinical setting by the senior author using a 6-point equal-appearing interval scale. Nasometer and pressure-flow results were not known to the senior author when making listener assessments. With a cutoff nasalance score of 32, the sensitivity of Nasometer ratings in correctly identifying the presence or absence of velopharyngeal areas in excess of 0.10 cm2 was 0.78 and 0.79, respectively. The sensitivity and specificity of nasometry in correctly identifying subjects with more than mild hypernasality in their speech was 0.89 while the specificity was 0.95. The results suggest that the Nasometer is an appropriate instrument that can be of value in assessing patients suspected of having velopharyngeal impairment. PMID:2069975

  15. 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. PMID:27044966

  16. Immature Platelet Fraction in Septic Patients: Clinical Relevance of Immature Platelet Fraction is Limited to the Sensitive and Accurate Discrimination of Septic Patients From Non-Septic Patients, Not to the Discrimination of Sepsis Severity

    PubMed Central

    Park, Sang Hyuk; Ha, Sang Ook; Cho, Young-Uk; Park, Chan-Jeoung

    2016-01-01

    Background The immature platelet fraction (IPF) reflects the degree of reticulated platelets. We evaluated performances of IPF as a biomarker for the discrimination of septic patients from non-septic patients and sepsis severity. Methods Total 312 patients admitted between March and July 2013 were enrolled and samples were obtained at admission. Lactate (LA), procalcitonin (PCT), C-reactive protein (CRP), immature granulocyte fraction (IG), immature reticulocyte fraction (IRF), and IPF were analyzed as sepsis biomarkers and their performances were compared. Results The performance of IPF (area under the curve [AUC]=0.868) in the discrimination of septic patients from non-septic patients was comparable to PCT/CRP/LA/IG (AUC=0.923/0.940/0.781/0.812, P=0.233/0.106/0.186/0.353, respectively), and was significantly better than the IRF (AUC=0.658, P=0.007). Sensitivity (89.8%, 95% confidence interval [CI] 84.9-99.8%) and accuracy (83.2%, 95% CI 78.8-90.0%) of IPF were the best among all biomarkers. The performance of IPF in discriminating septic patients from non-septic patients with local infection showed similar results. However, the IPF could not efficiently discriminate sepsis severity (AUC=0.599), similar to other biomarkers (AUC=0.519-0.752). Conclusions The IPF possessed high sensitivity/accuracy in discriminating septic patients from non-septic patients, regardless of local infection status. However, the IPF did not efficiently discriminate sepsis severity. The clinical relevance of IPF as a sepsis biomarker is, therefore, limited to sensitive and accurate discrimination of septic patients from non-septic patients, not discrimination of sepsis severity. PMID:26522752

  17. New strategies to identify patients harbouring antibiotic-resistant bacteria at hospital admission.

    PubMed

    Tacconelli, E

    2006-02-01

    Nosocomial infections caused by antibiotic-resistant bacteria are associated with high morbidity and mortality worldwide. Most prevention strategies focus on cross-transmission, but the endemic state inside the hospital is also maintained through the influx of patients colonised or infected with antibiotic-resistant bacteria, balanced by the efflux of colonised patients following discharge. Epidemiological research has demonstrated that eradication can be achieved by preventing the influx of resistant bacteria. The presence of a central venous catheter and a history of methicillin-resistant Staphylococcus aureus (MRSA) infection or colonisation are associated significantly with methicillin-resistant staphylococcal bacteraemia at admission. Previous antibiotic therapy and transfer from long-term care facilities or nursing homes are associated with bacteraemia caused by methicillin-resistant coagulase-negative staphylococci, while skin ulcer and cellulites are independent risk-factors for MRSA bacteraemia. A scoring system using point values has been developed and validated to identify patients positive for vancomycin-resistant enterococci at admission. Six variables were identified: age > 60 years (2 points); hospitalisation in the previous year (3); use of two or more antibiotics during the previous 30 days (3); transfer from another hospital or long-term care facility (3); a requirement for chronic haemodialysis (2); and a previous history of MRSA infection (4). With a point score cut-off of > or = 10, the specificity of this prediction rule is 98%. Knowledge of variables identifying patients at high risk for being colonised or infected with antibiotic-resistant bacteria may assist clinicians in targeting preventive measures and streamlining the use of vancomycin. Current studies are analysing risk-factors for harbouring multiresistant Gram-negative bacteria at hospital admission. PMID:16441446

  18. Identifying Quality Indicators Used by Patients to Choose Secondary Health Care Providers: A Mixed Methods Approach

    PubMed Central

    Zaman, Saman Sara; Kahlon, Gurnaaz Kaur; Naik, Aditi; Jessel, Amar Singh; Nanavati, Niraj; Shah, Akash; Cox, Benita; Darzi, Ara

    2015-01-01

    Background Patients in health systems across the world can now choose between different health care providers. Patients are increasingly using websites and apps to compare the quality of health care services available in order to make a choice of provider. In keeping with many patient-facing platforms, most services currently providing comparative information on different providers do not take account of end-user requirements or the available evidence base. Objective To investigate what factors were considered most important when choosing nonemergency secondary health care providers in the United Kingdom with the purpose of translating these insights into a ratings platform delivered through a consumer mHealth app. Methods A mixed methods approach was used to identify key indicators incorporating a literature review to identify and categorize existing quality indicators, a questionnaire survey to formulate a ranked list of performance indicators, and focus groups to explore rationales behind the rankings. Findings from qualitative and quantitative methodologies were mapped onto each other under the four categories identified by the literature review. Results Quality indicators were divided into four categories. Hospital access was the least important category. The mean differences between the other three categories hospital statistics, hospital staff, and hospital facilities, were not statistically significant. Staff competence was the most important indicator in the hospital staff category; cleanliness and up-to-date facilities were equally important in hospital facilities; ease of travel to the hospital was found to be most important in hospital access. All quality indicators within the hospital statistics category were equally important. Focus groups elaborated that users find it difficult to judge staff competence despite its importance. Conclusions A mixed methods approach is presented, which supported a patient-centered development and evaluation of a

  19. Identifying Important Risk Factors for Survival in Kidney Graft Failure Patients Using Random Survival Forests

    PubMed Central

    HAMIDI, Omid; POOROLAJAL, Jalal; FARHADIAN, Maryam; TAPAK, Leili

    2016-01-01

    Background: Kidney transplantation is the best alternative treatment for end-stage renal disease. Several studies have been devoted to investigate predisposing factors of graft rejection. However, there is inconsistency between the results. The objective of the present study was to utilize an intuitive and robust approach for variable selection, random survival forests (RSF), and to identify important risk factors in kidney transplantation patients. Methods: The data set included 378 patients with kidney transplantation obtained through a historical cohort study in Hamadan, western Iran, from 1994 to 2011. The event of interest was chronic nonreversible graft rejection and the duration between kidney transplantation and rejection was considered as the survival time. RSF method was used to identify important risk factors for survival of the patients among the potential predictors of graft rejection. Results: The mean survival time was 7.35±4.62 yr. Thirty-seven episodes of rejection were occurred. The most important predictors of survival were cold ischemic time, recipient’s age, creatinine level at discharge, donors’ age and duration of hospitalization. RSF method predicted survival better than the conventional Cox-proportional hazards model (out-of-bag C-index of 0.965 for RSF vs. 0.766 for Cox model and integrated Brier score of 0.081 for RSF vs. 0.088 for Cox model). Conclusion: A RSF model in the kidney transplantation patients outperformed traditional Cox-proportional hazard model. RSF is a promising method that may serve as a more intuitive approach to identify important risk factors for graft rejection. PMID:27057518

  20. Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs)

    PubMed Central

    2014-01-01

    Background Synthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example. Methods Systematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation. Results Searches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, ‘physical function’ in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains. Conclusion This study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials. PMID:24495582

  1. 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. PMID:23473290

  2. Quantitative ultrasound does not identify patients with an inflammatory disease at risk of vertebral deformities

    PubMed Central

    Heijckmann, A Caroline; Dumitrescu, Bianca; Nieuwenhuijzen Kruseman, Arie C; Geusens, Piet; Wolffenbuttel, Bruce HR; De Vries, Jolanda; Drent, Marjolein; Huijberts, Maya SP

    2008-01-01

    Background Previous studies from our group have shown that a high prevalence of vertebral deformities suggestive of fracture can be found in patients with an inflammatory disease, despite a near normal bone mineral density (BMD). As quantitative ultrasound (QUS) of the heel can be used for refined assessment of bone strength, we evaluated whether QUS can be used to identify subjects with an inflammatory disease with an increased chance of having a vertebral fracture. Methods 246 patients (mean age: 44 ± 12.4 years) with an inflammatory disease (sarcoidosis or inflammatory bowel disease (IBD)) were studied. QUS of the heel and BMD of the hip (by dual X-ray absorptiometry (DXA)) were measured. Furthermore lateral single energy densitometry of the spine for assessment of vertebral deformities was done. Logistic regression analysis was performed to assess the strength of association between the prevalence of a vertebral deformity and BMD and QUS parameters, adjusted for gender and age. Results Vertebral deformities (ratio of <0.80) were found in 72 vertebrae of 54 subjects (22%). In contrast to the QUS parameters BUA (broadband ultrasound attenuation) and SOS (speed of sound), T-score of QUS and T-scores of the femoral neck and trochanter (DXA) were lower in the group of patients with vertebral deformities. Logistic regression analysis showed that the vertebral deformity risk increases by about 60 to 90% per 1 SD reduction of BMD (T-score) determined with DXA but not with QUS. Conclusion Our findings imply that QUS measurements of the calcaneus in patients with an inflammatory condition, such as sarcoidosis and IBD, are likely of limited value to identify patients with a vertebral fracture. PMID:18492278

  3. Targeted Next Generation Sequencing Identifies Clinically Actionable Mutations in Patients with Melanoma

    PubMed Central

    Jeck, William R.; Parker, Joel; Carson, Craig C.; Shields, Janiel M.; Sambade, Maria J.; Peters, Eldon C.; Burd, Christin E.; Thomas, Nancy E.; Chiang, Derek Y.; Liu, Wenjin; Eberhard, David A.; Ollila, David; Grilley-Olson, Juneko; Moschos, Stergios; Hayes, D. Neil; Sharpless, Norman E.

    2014-01-01

    Somatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here we describe a NextGen sequencing approach to fully analyze 248 genes, including all those of known clinical significance in melanoma. This strategy features solution capture of DNA followed by multiplexed, high-throughput sequencing, and was evaluated in 31 melanoma cell lines and 18 tumor tissues from patients with metastatic melanoma. Mutations in melanoma cell lines correlated with their sensitivity to corresponding small molecule inhibitors, confirming, for example, lapatinib sensitivity in ERBB4 mutant lines and identifying a novel activating mutation of BRAF. The latter event would not have been identified by clinical sequencing and was associated with responsiveness to a BRAF kinase inhibitor. This approach identified focal copy number changes of PTEN not found by standard methods, such as comparative genomic hybridization (CGH). Actionable mutations were found in 89% of the tumor tissues analyzed, 56% of which would not be identified by standard-of-care approaches. This work shows that targeted sequencing is an attractive approach for clinical use in melanoma. PMID:24628946

  4. Stratified neutrophil-to-lymphocyte ratio accurately predict mortality risk in hepatocellular carcinoma patients following curative liver resection

    PubMed Central

    Huang, Gui-Qian; Zhu, Gui-Qi; Liu, Yan-Long; Wang, Li-Ren; Braddock, Martin; Zheng, Ming-Hua; Zhou, Meng-Tao

    2016-01-01

    Objectives Neutrophil lymphocyte ratio (NLR) has been shown to predict prognosis of cancers in several studies. This study was designed to evaluate the impact of stratified NLR in patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods A total of 1659 patients who underwent CLR for suspected HCC between 2007 and 2014 were reviewed. The preoperative NLR was categorized into quartiles based on the quantity of the study population and the distribution of NLR. Hazard ratios (HRs) and 95% confidence intervals (CIs) were significantly associated with overall survival (OS) and derived by Cox proportional hazard regression analyses. Univariate and multivariate Cox proportional hazard regression analyses were evaluated for association of all independent parameters with disease prognosis. Results Multivariable Cox proportional hazards models showed that the level of NLR (HR = 1.031, 95%CI: 1.002-1.060, P = 0.033), number of nodules (HR = 1.679, 95%CI: 1.285-2.194, P<0.001), portal vein thrombosis (HR = 4.329, 95%CI: 1.968-9.521, P<0.001), microvascular invasion (HR = 2.527, 95%CI: 1.726-3.700, P<0.001) and CTP score (HR = 1.675, 95%CI: 1.153-2.433, P = 0.007) were significant predictors of mortality. From the Kaplan-Meier analysis of overall survival (OS), each NLR quartile showed a progressively worse OS and apparent separation (log-rank P=0.008). The highest 5-year OS rate following CLR (60%) in HCC patients was observed in quartile 1. In contrast, the lowest 5-year OS rate (27%) was obtained in quartile 4. Conclusions Stratified NLR may predict significantly improved outcomes and strengthen the predictive power for patient responses to therapeutic intervention. PMID:26716411

  5. Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD

    PubMed Central

    Morais, Sara; Bastos-Ferreira, Rita; Sequeiros, Jorge

    2016-01-01

    Objectives: To identify the genomic mechanisms that result in PARK2 large gene deletions. Methods: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with symptoms of Parkinson disease. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification, followed by long-range PCR and sequencing to map deletion breakpoints. Results: We identified biallelic pathogenic parkin mutations in 40 of the 244 patients. There were 18 different mutations, some of them novel. This study included mapping of 17 deletion breakpoints showing that nonhomologous end joining is the most common mechanism responsible for these gene rearrangements. None of these deletion breakpoints were previously described, and only one was present in 2 unrelated families, indicating that most of the deletions result from independent events. Conclusions: The c.155delA mutation is highly prevalent in the Portuguese population (62.5% of the cases). Large deletions were present in 42.5% of the patients. We present the largest study on the molecular mechanisms that mediate PARK2 deletions in a homogeneous population. PMID:27182553

  6. A High Malaria Prevalence Identified by PCR among Patients with Acute Undifferentiated Fever in India

    PubMed Central

    Haanshuus, Christel Gill; Chandy, Sara; Manoharan, Anand; Vivek, Rosario; Mathai, Dilip; Xena, Deepika; Singh, Ashita; Langeland, Nina; Blomberg, Bjørn; Vasanthan, George; Sitaram, Usha; Appasamy, Jonathan; Nesaraj, Joel; Henry, Anil; Patil, Suvarna; Alvarez-Uria, Gerardo; Armstrong, Lois; Mørch, Kristine

    2016-01-01

    Background Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. Methods During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. Results The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. Conclusions High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria. PMID:27389396

  7. 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

  8. Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

    PubMed

    Marrazzo, Antonio; Taormina, Pietra; Gebbiab, Vittorio; David, Massimo; Riili, Ignazio; Lo Gerfo, Domenico; Casà, Luigi; Noto, Antonio

    2007-01-01

    Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that

  9. 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

  10. High natural killer cell number might identify stroke patients at risk of developing infections

    PubMed Central

    De Vos, Aurelie; Van Binst, Anne-Marie; De Waele, Marc; Coomans, Danny; Buyl, Ronald; De Keyser, Jacques

    2015-01-01

    Objective: To investigate early changes in leukocyte subsets and autonomic function as predictors of the development of poststroke infections. Methods: We assessed the time course of leukocyte subsets in the blood of 59 patients with acute ischemic stroke. We divided the patients into 2 groups: those who developed infections during the first 7 days after stroke onset and those who did not. We measured urinary norepinephrine and epinephrine concentrations and pulse rate variability indices within 24 hours of admission. Results: We found that the number of circulating natural killer (NK) cells within the first hours after stroke was higher in stroke patients who developed infections (mean 435 cells/mL; 95% confidence interval [CI] 321–588) than in stroke patients who did not develop infections (mean 236 cells/mL; 95% CI 186–300; p = 0.001). This was followed by a decrease in all lymphocyte subsets from admission to day 1, varying between 22% and 40%, which was not seen in patients without poststroke infection (mean increase varied between 2% and 23%; all p < 0.005). In the group that developed infections, pulse rate variability revealed a decreased high frequency component. These findings all remained significant after adjustment for age and stroke volume. Conclusions: High circulating NK cell count within the first hours after ischemic stroke onset followed by a drop in all lymphocyte subsets identified patients who developed infections and may be caused by a sympathovagal imbalance with sympathetic overweight. These findings need to be validated in larger studies. PMID:25738168

  11. A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder.

    PubMed

    Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H Henry; Mysorekar, Indira U; Jain, Sanjay

    2016-07-01

    Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. PMID:27029431

  12. 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. PMID:27156907

  13. Identifying the Basal Ganglia Network Model Markers for Medication-Induced Impulsivity in Parkinson's Disease Patients

    PubMed Central

    Balasubramani, Pragathi Priyadharsini; Chakravarthy, V. Srinivasa; Ali, Manal; Ravindran, Balaraman; Moustafa, Ahmed A.

    2015-01-01

    Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its

  14. 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.

  15. Whole Exome Sequencing Identifies Mutations in Usher Syndrome Genes in Profoundly Deaf Tunisian Patients

    PubMed Central

    Riahi, Zied; Bonnet, Crystel; Zainine, Rim; Lahbib, Saida; Bouyacoub, Yosra; Bechraoui, Rym; Marrakchi, Jihène; Hardelin, Jean-Pierre; Louha, Malek; Largueche, Leila; Ben Yahia, Salim; Kheirallah, Moncef; Elmatri, Leila; Besbes, Ghazi; Abdelhak, Sonia; Petit, Christine

    2015-01-01

    Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss. PMID:25798947

  16. A novel protocol to identify mutations in patients with wiskott-Aldrich syndrome.

    PubMed

    Jones, L N; Lutskiy, M I; Cooley, J; Kenney, D M; Rosen, F S; Remold-O'Donnell, E

    2002-01-01

    Mutations of WASP (Wiskott-Aldrich syndrome protein) underlie the severe immunodeficiency/platelet disorder Wiskott-Aldrich syndrome (WAS) and its milder variant X-linked thrombocytopenia (XLT). The affected gene, a 12-exon structure on the X-chromosome, is expressed exclusively in blood cells. The encoded product WASP is a 502-amino-acid scaffolding protein that functions in stimulus-induced nucleation of actin filaments to form dynamic cell surface projections. To date, more than 150 mutations have been identified in 300 WAS/XLT kindred worldwide, generally through methodologies that include sophisticated exon screening steps such as single-strand conformation analysis. We report here a simpler protocol, which was designed for use in clinical settings to identify the mutations of newly diagnosed patients. The approach relies on directly sequencing amplified exons according to a staggered schedule based on statistical evaluation of previous cases. In a 2 1/2-year trial, samples from 28 consecutive patients were analyzed; these included 3 "blindly labeled" previously studied cases. The mutations that were identified include a broad spectrum (8 missense, 3 nonsense, 5 splice site mutations, 11 small insertion/deletions, 1 large deletion) and were broadly distributed (in 10 of the 12 exons). All mutations were verified and no discrepancies were encountered. Per patient, a mean of six DNA sequencing reactions and 6-7 h of staff effort sufficed for mutation identification and verification, indicating that the protocol is cost-effective. This cumulative experience demonstrates the suitability, reliability, and versatility of the new protocol. PMID:12367583

  17. Predictors of Extubation Failure in Neurocritical Patients Identified by a Systematic Review and Meta-Analysis

    PubMed Central

    Huang, Kaibin; Lin, Zhenzhou; Qiao, Weiguang; Pan, Suyue

    2014-01-01

    Background Prediction of extubation failure, particularly in neurocritical patients, is unique and controversial. We conducted a systematic review and meta-analysis to identify the risk factors for extubation failure in these patients. Methods A literature search of databases (MEDLINE, EMBASE, the Cochrane Library, and Web of Science) was performed up to August of 2013 to identify trials that evaluated extubation failure predictors. Included trials were either prospective or retrospective cohort studies. Results Nine studies involving 928 participants were included. The systematic review and meta-analysis revealed that the following were predictive for extubation failure: pneumonia, atelectasis, mechanical ventilation of >24 h, a low Glasgow Coma Scale score (7–9T) (OR = 4.96, 95% CI = 1.61–15.26, P = 0.005), the inability to follow commands (OR = 2.07, 95% CI = 1.15–3.71, P = 0.02), especially the command to close the eyes, thick secretion, and no intact gag reflex. Meanwhile, the following were not predictive for extubation failure: sex, secretion volume, coughing upon suctioning, and the inability to follow one command among showing two fingers, wiggling the toes, or coughing on command. Additionally, some traditional weaning parameters were shown to poorly predict extubation failure in neurocritical patients. Conclusions Besides pneumonia, atelectasis, and the duration of mechanical ventilation, other factors that should be taken into consideration in the prediction of extubation failure when neurocritical patients are weaned from tracheal intubation include neurologic abilities (Glasgow Coma Scale score and following commands), the secretion texture, and the presence of a gag reflex. PMID:25486091

  18. Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients

    PubMed Central

    Hashem, Somaya; Esmat, Gamal; Elakel, Wafaa; Habashy, Shahira; Abdel Raouf, Safaa; Darweesh, Samar; Soliman, Mohamad; Elhefnawi, Mohamed; El-Adawy, Mohamed; ElHefnawi, Mahmoud

    2016-01-01

    Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0–F2) or advanced (F3-F4) fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy. PMID:26880886

  19. Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients.

    PubMed

    Hashem, Somaya; Esmat, Gamal; Elakel, Wafaa; Habashy, Shahira; Abdel Raouf, Safaa; Darweesh, Samar; Soliman, Mohamad; Elhefnawi, Mohamed; El-Adawy, Mohamed; ElHefnawi, Mahmoud

    2016-01-01

    Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0-F2) or advanced (F3-F4) fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy. PMID:26880886

  20. 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

  1. 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

  2. Clinical decision aids for chest pain in the emergency department: identifying low-risk patients

    PubMed Central

    Alley, William; Mahler, Simon A

    2015-01-01

    Chest pain is one of the most common presenting complaints in the emergency department, though only a small minority of patients are subsequently diagnosed with acute coronary syndrome (ACS). However, missing the diagnosis has potential for significant morbidity and mortality. ACS presentations can be atypical, and their workups are often prolonged and costly. In order to risk-stratify patients and better direct the workup and care given, many decision aids have been developed. While each may have merit in certain clinical settings, the most useful aid in the emergency department is one that finds all cases of ACS while also identifying a substantial subset of patients at low risk who can be discharged without stress testing or coronary angiography. This review describes several of the chest pain decision aids developed and studied through the recent past, starting with the thrombolysis in myocardial infarction (TIMI) risk score and Global Registry of Acute Coronary Events (GRACE) scores, which were developed as prognostic aids for patients already diagnosed with ACS, then subsequently validated in the undifferentiated chest pain population. Asia-Pacific Evaluation of Chest Pain Trial (ASPECT); Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins (ADAPT); North American Chest Pain Rule (NACPR); and History, Electrocardiogram, Age, Risk factors, Troponin (HEART) score have been developed exclusively for use in the undifferentiated chest pain population as well, with improved performance compared to their predecessors. This review describes the relative merits and limitations of these decision aids so that providers can determine which tool fits the needs of their clinical practice setting. PMID:27147894

  3. 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

  4. 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

  5. Identifying nutritional, functional, and quality of life correlates with male hypogonadism in advanced cancer patients

    PubMed Central

    Fuoco, Domenico; di Tomasso, Jonathan; Boulos, Caroline; Kilgour, Robert D; Morais, Jose A; Borod, Manuel; Vigano, Antonio

    2015-01-01

    With the availability of a potential treatment to reverse male hypogonadism (MH), the primary aim of this case series study was to determine independent relationships between this condition and the nutritional, functional, and quality of life characteristics of advanced cancer patients (ACP). Free testosterone levels were measured in 100 male patients with advanced lung and gastrointestinal (GI) cancer. Routine blood markers of nutrition and inflammation, self-reporting questionnaires for symptom, nutrition, and functional status along with handgrip dynamometry were assessed for all patients at bedside. Almost half of this cohort underwent further assessments (body composition, lower body strength, in depth quality of life and fatigue questionnaires) at the McGill Nutrition and Performance Laboratory (mnupal.mcgill.ca). Multiple regression analyses were performed to identify independent correlations between free testosterone and the above measures. Seventy-six percent of patients were diagnosed with MH. Using multiple linear regression, low free testosterone (31.2 pmol/L) was independently associated with lower albumin (B = –3.8 g/L; 95% confidence interval CI –6.8:–0.8), muscle strength (–11.7 lbs; –20.4: –3.0) and mass in upper limbs (–0.8 kg; –1.4: –0.1), overall performance status (Eastern Cooperative Oncology Group Performance Scale, ECOG PS 0.6; 0.1:1.1), cancer-related fatigue (Brief Fatigue Inventory, BFI 16.7; 2.0: 31.3), and overall quality of life (MQoL total score –1.42; –2.5: –0.3). Thus MH seems to be highly prevalent in ACP, and it is independently associated with important nutritional, functional, and quality of life characteristics in this patient population. PMID:26316882

  6. 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

  7. 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.

  8. Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications?

    PubMed Central

    Charlson, M E; MacKenzie, C R; Gold, J P; Ales, K L; Topkins, M; Shires, G T

    1990-01-01

    While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure

  9. How do clinical features help identify paediatric patients with fractures following blunt wrist trauma?

    PubMed Central

    Webster, A P; Goodacre, S; Walker, D; Burke, D

    2006-01-01

    Objective Wrist injuries are a common presentation to the emergency department (ED). There are no validated decision rules to help clinicians evaluate paediatric wrist trauma. This study aimed to identify which clinical features are diagnostically useful in deciding the need for a wrist radiograph, and then to develop a clinical decision rule. Methods This prospective cohort study was carried out in the ED of Sheffield Children's Hospital. Eligible patients were recruited if presenting within 72 hours following blunt wrist trauma. A standardised data collection form was completed for all patients. The outcome measure was the presence or absence of a fracture. Univariate analysis was performed with the χ2 test. Associated variables (p<0.2) were entered into a multivariate model. Classification and regression tree (CART) analysis was used to derive the clinical decision rule. Results In total, 227 patients were recruited and 106 children were diagnosed with fractures (47%). Of 10 clinical features analysed, six were found by univariate analysis to be associated with a fracture. CART analysis identified the presence of radial tenderness, focal swelling, or an abnormal supination/pronation as the best discriminatory features. Cross fold validation of this decision rule had a sensitivity of 99.1% (95% confidence interval 94.8% to 100%) and a specificity of 24.0% (17.2% to 32.3%). The radiography rate would be 87%. Conclusions Radial tenderness, focal swelling, and abnormal supination/pronation are associated with wrist fractures in children. The clinical decision rule derived from these features had a high sensitivity, but low specificity, and would not substantially alter our current radiography rate. The potential for a clinical decision rule for paediatric wrist trauma appears limited. PMID:16627835

  10. Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells

    PubMed Central

    Carstens, Matthew R.; Fisher, Robert C.; Acharya, Abhinav P.; Butterworth, Elizabeth A.; Scott, Edward; Huang, Emina H.; Keselowsky, Benjamin G.

    2015-01-01

    A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs. PMID:26124098

  11. Urinary Bladder Paragangliomas: How Immunohistochemistry Can Assist to Identify Patients With SDHB Germline and Somatic Mutations.

    PubMed

    Giubellino, Alessio; Lara, Karlena; Martucci, Victoria; Huynh, Than; Agarwal, Piyush; Pacak, Karel; Merino, Maria J

    2015-11-01

    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, as these patients have a more aggressive disease. Eleven tumors from these patients were stained by IHC. Six of 11 tumors were negative for SDHB staining by IHC with no cytoplasmic staining in tumor cells when compared with normal tissues. Five 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 SDHA 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 this is the first study to demonstrate that somatic mutations can be recognized by IHC staining. PMID:26457353

  12. Utility of vital signs, heart rate variability and complexity, and machine learning for identifying the need for lifesaving interventions in trauma patients.

    PubMed

    Liu, Nehemiah T; Holcomb, John B; Wade, Charles E; Darrah, Mark I; Salinas, Jose

    2014-08-01

    To date, no studies have attempted to utilize data from a combination of vital signs, heart rate variability and complexity (HRV, HRC), as well as machine learning (ML), for identifying the need for lifesaving interventions (LSIs) in trauma patients. The objectives of this study were to examine the utility of the above for identifying LSI needs and compare different LSI-associated models, with the hypothesis that an ML model would be superior in performance over multivariate logistic regression models. One hundred four patients transported from the injury scene via helicopter were selected for the study. A wireless vital signs monitor was attached to the patient's arm and used to capture physiologic data, including HRV and HRC. The power of vital sign measurements, HRV, HRC, and Glasgow Coma Scale score (GCS) to identify patients requiring LSIs was estimated using multivariate logistic regression and ML. Receiver operating characteristic (ROC) curves were also obtained. Thirty-two patients underwent 75 LSIs. After logistic regression, ROC curves demonstrated better identification for LSIs using heart rate (HR) and HRC (area under the curve [AUC] of 0.81) than using HR alone (AUC of 0.73). Likewise, ROC curves demonstrated better identification for LSIs using GCS and HRC (AUC of 0.94) than using GCS and HR (AUC of 0.92). Importantly, ROC curves demonstrated that an ML model using HR, GCS, and HRC (AUC of 0.99) had superior performance over multivariate logistic regression models for identifying the need for LSIs in trauma patients. Development of computer decision support systems should utilize vital signs, HRC, and ML in order to achieve more accurate diagnostic capabilities, such as identification of needs for LSIs in trauma patients. PMID:24727872

  13. Identifying target groups for the prevention of depression among caregivers of dementia patients

    PubMed Central

    Joling, Karlijn J.; Smit, Filip; van Marwijk, Harm W. J.; van der Horst, Henriëtte E.; Scheltens, Philip; Schulz, Richard; van Hout, Hein P. J.

    2014-01-01

    Background Depression in informal caregivers of persons with dementia is a major, costly and growing problem. However, it is not yet clear which caregivers are at increased risk of developing depression. With this knowledge preventive strategies could focus on these groups to maximize health gain and minimize effort. Methods The onset of clinically relevant depression was measured with the Center for Epidemiologic Studies - Depression Scale in 725 caregivers who were not depressed at baseline and who were providing care for a relative with dementia. Caregivers were followed over 18 months. The indices calculated to identify the most important risk indicators were: odds ratio, attributable fraction, exposure rate and number needing to be treated. Results The following significant indicators of depression onset were identified: increased initial depressive symptoms, poor self-rated health status and white or Hispanic race/ethnicity. The incidence of depression would decrease by 72.3% (attributive fraction) if these risk indicators together are targeted by a completely effective intervention. Race/ethnicity was not a significant predictor if caregivers of patients who died or were institutionalized were left out of the analyses. Conclusion Detection of only a few characteristics makes it possible to identify high-risk groups in an efficient way. Focusing on these easy-to-assess characteristics might contribute to a cost-effective prevention of depression in caregivers. PMID:21880175

  14. 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. PMID:27138061

  15. 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

  16. Online Discourse on Fibromyalgia: Text-Mining to Identify Clinical Distinction and Patient Concerns

    PubMed Central

    Park, Jungsik; Ryu, Young Uk

    2014-01-01

    Background The purpose of this study was to evaluate the possibility of using text-mining to identify clinical distinctions and patient concerns in online memoires posted by patients with fibromyalgia (FM). Material/Methods A total of 399 memoirs were collected from an FM group website. The unstructured data of memoirs associated with FM were collected through a crawling process and converted into structured data with a concordance, parts of speech tagging, and word frequency. We also conducted a lexical analysis and phrase pattern identification. After examining the data, a set of FM-related keywords were obtained and phrase net relationships were set through a web-based visualization tool. Results The clinical distinction of FM was verified. Pain is the biggest issue to the FM patients. The pains were affecting body parts including ‘muscles,’ ‘leg,’ ‘neck,’ ‘back,’ ‘joints,’ and ‘shoulders’ with accompanying symptoms such as ‘spasms,’ ‘stiffness,’ and ‘aching,’ and were described as ‘sever,’ ‘chronic,’ and ‘constant.’ This study also demonstrated that it was possible to understand the interests and concerns of FM patients through text-mining. FM patients wanted to escape from the pain and symptoms, so they were interested in medical treatment and help. Also, they seemed to have interest in their work and occupation, and hope to continue to live life through the relationships with the people around them. Conclusions This research shows the potential for extracting keywords to confirm the clinical distinction of a certain disease, and text-mining can help objectively understand the concerns of patients by generalizing their large number of subjective illness experiences. However, it is believed that there are limitations to the processes and methods for organizing and classifying large amounts of text, so these limits have to be considered when analyzing the results. The development of research methodology to overcome

  17. Team effort identifies opportunities to reduce wait times, improve safety for patients.

    PubMed

    2013-07-01

    The ED at Avera Marshall Regional Medical Center in Marshall, MN, has been able to implement a number of improvements in its throughput process by holding monthly "quick hits" meetings aimed at identifying opportunities for improvement and potential solutions. Among the improvements that grew out of this process is a 12-minute dent in the ED's average decision-to-admit times. Administrators say a collaborative culture has been key to keeping the meetings positive and productive. The "quick hits" meetings typically included nurses, an ED physician, two representatives from the hospital's quality department, and representatives from lab or X-ray as needed. The ED director scheduled the meetings during the morning hours when the ED is typically not busy, and the physician has time to attend. Decision-to-admit times were reduced by giving charge nurses an earlier notification when patients presenting to the ED were likely to be admitted. PMID:23828969

  18. 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

  19. 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

  20. Identifying Patients with Bacteremia in Community-Hospital Emergency Rooms: A Retrospective Cohort Study

    PubMed Central

    Takeshima, Taro; Yamamoto, Yosuke; Noguchi, Yoshinori; Maki, Nobuyuki; Gibo, Koichiro; Tsugihashi, Yukio; Doi, Asako; Fukuma, Shingo; Yamazaki, Shin; Kajii, Eiji; Fukuhara, Shunichi

    2016-01-01

    Objectives (1) To develop a clinical prediction rule to identify patients with bacteremia, using only information that is readily available in the emergency room (ER) of community hospitals, and (2) to test the validity of that rule with a separate, independent set of data. Design Multicenter retrospective cohort study. Setting To derive the clinical prediction rule we used data from 3 community hospitals in Japan (derivation). We tested the rule using data from one other community hospital (validation), which was not among the three “derivation” hospitals. Participants Adults (age ≥ 16 years old) who had undergone blood-culture testing while in the ER between April 2011 and March 2012. For the derivation data, n = 1515 (randomly sampled from 7026 patients), and for the validation data n = 467 (from 823 patients). Analysis We analyzed 28 candidate predictors of bacteremia, including demographic data, signs and symptoms, comorbid conditions, and basic laboratory data. Chi-square tests and multiple logistic regression were used to derive an integer risk score (the “ID-BactER” score). Sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (i.e., the AUC) were computed. Results There were 241 cases of bacteremia in the derivation data. Eleven candidate predictors were used in the ID-BactER score: age, chills, vomiting, mental status, temperature, systolic blood pressure, abdominal sign, white blood-cell count, platelets, blood urea nitrogen, and C-reactive protein. The AUCs was 0.80 (derivation) and 0.74 (validation). For ID-BactER scores ≥ 2, the sensitivities for derivation and validation data were 98% and 97%, and specificities were 20% and 14%, respectively. Conclusions The ID-BactER score can be computed from information that is readily available in the ERs of community hospitals. Future studies should focus on developing a score with a higher specificity while maintaining the desired sensitivity

  1. 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

  2. Novel Dielectric Coagulometer Identifies Hypercoagulability in Patients with a High CHADS2 Score without Atrial Fibrillation

    PubMed Central

    Hasegawa, Yuki; Hamada, Satomi; Nishimura, Takuro; Sasaki, Takeshi; Ebana, Yusuke; Kawabata, Mihoko; Goya, Masahiko; Isobe, Mitsuaki; Koyama, Takatoshi; Furukawa, Tetsushi; Hirao, Kenzo

    2016-01-01

    Background Recent reports showed that the CHADS2 score predicted the risk of strokes in patients without atrial fibrillation (AF). Although the hypercoagulability may contribute to the thrombogenesis, it has not been fully investigated due to a lack of a sensitive evaluation modality. Recently a novel dielectric blood coagulometry (DBCM) was invented for evaluating the coagulability by measuring the temporal change in whole blood dielectric permittivity. Objective We evaluated the utility of the DBCM for identifying the coagulability. Patients/Methods For fundamental experiments, 133 citrated blood samples were drawn from subjects with or without heparin administration. A DBCM analysis was performed to find the adequate coagulation index, and to delineate its measurement range by adding recombinant human tissue factor (TF) or heparin. Then the coagulability was assessed by DBCM and conventional coagulation assays in 84 subjects without AF, who were divided into 3 groups by their CHADS2 score. Another 17 patients who received warfarin were also assessed by DBCM to evaluate the effect of anticoagulants. Results and Conclusions We calculated the derivative of the dielectric permittivity change after recalcification, and extracted the end of acceleration time (EAT) as a novel index. The EAT showed a dose-dependent shortening with the addition of serial dilutions of TF (×10−2 to ×10−4), and a dose-dependent prolongation with the addition of heparin (0.05 to 0.15 U/ml). The EAT was significantly shorter in the higher CHADS2 score group (19.8 ± 4.8, 18.6 ± 3.1, and 16.3 ± 2.7 min in the CHADS2 = 0, 1, and ≥2 groups, respectively, p = 0.0065 by ANOVA). Patients receiving warfarin had a significantly more prolonged EAT than those without warfarin (18.6±4.2 vs. 25.8±7.3 min, p <0.001). DBCM detected the whole blood coagulability with a high sensitivity. Subjects with higher CHADS2 scores exhibited hypercoagulability without AF. PMID:27275926

  3. Postanesthesia patients with large upper arm circumference: is use of an "extra-long" adult cuff or forearm cuff placement accurate?

    PubMed

    Watson, Sheri; Aguas, Marita; Bienapfl, Tracy; Colegrove, Pat; Foisy, Nancy; Jondahl, Bonnie; Yosses, Mary Beth; Yu, Larissa; Anastas, Zoe

    2011-06-01

    The purpose of this study was to determine if blood pressure (BP) measured in the forearm or with an extra-long BP cuff in the upper arm accurately reflects BP measured in the upper arm with an appropriately sized BP cuff in patients with large upper arm circumference. A method-comparison design was used with a convenience sample of 49 PACU patients. Noninvasive blood pressures were obtained in two different locations (forearm; upper arm) and in the upper arm with an extra-long adult and recommended large adult cuff sizes. Data were analyzed by calculating bias and precision for the BP cuff size and location and Student's t-tests, with P < .0125 considered significant. Significantly higher forearm systolic (P < .0001) and diastolic (P < .0002) BP measurements were found compared to BP obtained in the upper arm with the reference standard BP cuff. Significantly higher systolic (t(48df) = 5.38, P < .0001), but not diastolic (t(48df) = 4.11, P < .019), BP differences were found for BP measured with the extra-long cuff at the upper arm site compared to the upper arm, reference standard BP. Findings suggest that the clinical practice of using the forearm or an extra-long cuff in the upper arm for BP measurement in post anesthesia patients with large upper arm circumferences may result in inaccurate BP values. PMID:21641528

  4. 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. PMID:26516075

  5. DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.

    PubMed

    Ashktorab, Hassan; Daremipouran, M; Goel, Ajay; Varma, Sudhir; Leavitt, R; Sun, Xueguang; Brim, Hassan

    2014-04-01

    The identification of genes that are differentially methylated in colorectal cancer (CRC) has potential value for both diagnostic and therapeutic interventions specifically in high-risk populations such as African Americans (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been systematically explored and remain poorly understood. Here, we performed DNA methylome profiling to identify the methylation status of CpG islands within candidate genes involved in critical pathways important in the initiation and development of CRC. We used reduced representation bisulfite sequencing (RRBS) in colorectal cancer and adenoma tissues that were compared with DNA methylome from a healthy AA subject's colon tissue and peripheral blood DNA. The identified methylation markers were validated in fresh frozen CRC tissues and corresponding normal tissues from AA patients diagnosed with CRC at Howard University Hospital. We identified and validated the methylation status of 355 CpG sites located within 16 gene promoter regions associated with CpG islands. Fifty CpG sites located within CpG islands-in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1), GPR75 (24), and TNFAIP2 (1)-were significantly hypermethylated in tumor vs. normal tissues (P<0.05). The methylation status of BMP3, EID3, GAS7, and GPR75 was confirmed in an independent, validation cohort. Ingenuity pathway analysis mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-β1 network-the two key pathways in CRC. In addition to hypermethylated genes, our analysis also revealed that LINE-1 repeat elements were progressively hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA methylome profiling based on RRBS is an effective method for screening aberrantly methylated genes in CRC. While previous studies focused on the limited identification of hypermethylated genes, ours is the first study to systematically and comprehensively identify novel hypermethylated

  6. 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.

  7. B56δ-related protein phosphatase 2A dysfunction identified in patients with intellectual disability

    PubMed Central

    Houge, Gunnar; Haesen, Dorien; Vissers, Lisenka E.L.M.; Mehta, Sarju; Parker, Michael J.; Wright, Michael; Vogt, Julie; McKee, Shane; Tolmie, John L.; Cordeiro, Nuno; Kleefstra, Tjitske; Willemsen, Marjolein H.; Reijnders, Margot R.F.; Berland, Siren; Hayman, Eli; Lahat, Eli; Brilstra, Eva H.; van Gassen, Koen L.I.; Zonneveld-Huijssoon, Evelien; de Bie, Charlotte I.; Hoischen, Alexander; Eichler, Evan E.; Holdhus, Rita; Steen, Vidar M.; Døskeland, Stein Ove; Hurles, Matthew E.; FitzPatrick, David R.; Janssens, Veerle

    2015-01-01

    Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function. Ten patients had mutations within a highly conserved acidic loop of the PPP2R5D-encoded B56δ regulatory subunit, with the same E198K mutation present in 6 individuals. Five patients had mutations in the PPP2R1A-encoded scaffolding Aα subunit, with the same R182W mutation in 3 individuals. Some Aα cases presented with large ventricles, causing macrocephaly and hydrocephalus suspicion, and all cases exhibited partial or complete corpus callosum agenesis. Functional evaluation revealed that mutant A and B subunits were stable and uncoupled from phosphatase activity. Mutant B56δ was A and C binding–deficient, while mutant Aα subunits bound B56δ well but were unable to bind C or bound a catalytically impaired C, suggesting a dominant-negative effect where mutant subunits hinder dephosphorylation of B56δ-anchored substrates. Moreover, mutant subunit overexpression resulted in hyperphosphorylation of GSK3β, a B56δ-regulated substrate. This effect was in line with clinical observations, supporting a correlation between the ID degree and biochemical disturbance. PMID:26168268

  8. New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy

    PubMed Central

    Marchant, D; Yu, K; Bigot, K; Roche, O; Germain, A; Bonneau, D; Drouin‐Garraud, V; Schorderet, D F; Munier, F; Schmidt, D; Neindre, P Le; Marsac, C; Menasche, M; Dufier, J L; Fischmeister, R; Hartzell, C; Abitbol, M

    2007-01-01

    Purpose The mutations responsible for Best vitelliform macular dystrophy (BVMD) are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein named bestrophin‐1 (hBest1) which is a Ca2+‐sensitive chloride channel. This study was performed to identify disease‐specific mutations in 27 patients with BVMD. Because this disease is characterised by an alteration in Cl− channel function, patch clamp analysis was used to test the hypothesis that one of the VMD2 mutated variants causes the disease. Methods Direct sequencing analysis of the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of hBest1 was expressed in HEK‐293 cells and the associated Cl− current was examined using whole‐cell patch clamp analysis. Results Six new VMD2 mutations were identified, located exclusively in exons four, six and eight. One of these mutations (Q293H) was particularly severe. Patch clamp analysis of human embryonic kidney cells expressing the Q293H mutant showed that this mutant channel is non‐functional. Furthermore, the Q293H mutant inhibited the function of wild‐type bestrophin‐1 channels in a dominant negative manner. Conclusions This study provides further support for the idea that mutations in VMD2 are a necessary factor for Best disease. However, because variable expressivity of VMD2 was observed in a family with the Q293H mutation, it is also clear that a disease‐linked mutation in VMD2 is not sufficient to produce BVMD. The finding that the Q293H mutant does not form functional channels in the membrane could be explained either by disruption of channel conductance or gating mechanisms or by improper trafficking of the protein to the plasma membrane. PMID:17287362

  9. Does Preendoscopy Rockall Score Safely Identify Low Risk Patients following Upper Gastrointestinal Haemorrhage?

    PubMed Central

    Johnston, Matthew R.; Murray, Iain A.; Schultz, Michael; McLeod, Peter; O'Donnell, Nathan; Norton, Heather; Baines, Chelsea; Fawcett, Emily; Fesaitu, Terry; Leung, Hin; Park, Jeong-Yoon; Salleh, Adibah; Zhang, Wei; García, José A.

    2015-01-01

    Objective. To determine if preendoscopy Rockall score (PERS) enables safe outpatient management of New Zealanders with upper gastrointestinal haemorrhage (UGIH). Methods. Retrospective analysis of adults with UGIH over 59 consecutive months. PERS, diagnosis, demographics, need for endoscopic therapy, transfusion or surgery and 30-day mortality and 14-day rebleeding rate, and sensitivity and specificity of PERS for enabling safe discharge preendoscopy were calculated. Results. 424 admissions with UGIH. Median age was 74.3 years (range 19–93 years), with 55.1% being males. 30-day mortality was 4.6% and 14-day rebleeding rate was 6.0%. Intervention was required in 181 (46.6%): blood transfusion (147 : 37.9%), endoscopic intervention (75 : 19.3%), and surgery (8 : 2.1%). 42 (10.8%) had PERS = 0 with intervention required in 15 (35.7%). Females more frequently required intervention, OR 1.73 (CI: 1.12–2.69). PERS did not predict intervention but did predict 30-day mortality: each point increase equated to an increase in mortality of OR 1.46 (CI: 1.11–1.92). Taking NSAIDs/aspirin reduced 30-day mortality, OR 0.22 (CI: 0.08–0.60). Conclusion. PERS identifies 10.8% of those with UGIH as low risk but 35.7% required intervention or died. It has a limited role in assessing these patients and should not be used to identify those suitable for outpatient endoscopy. PMID:26089867

  10. Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

    PubMed Central

    2011-01-01

    Background Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH. Methods A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay. Results Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6%) chromosomes. The most frequent mutation was I2 splice (27%) followed by Ile173Asn (26%), Arg 357 Trp (19%), Gln319stop, 16% and Leu308InsT (12%), whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state. Conclusion Our study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined. PMID:21329531

  11. Patient-specific coronary stenoses can be modeled using a combination of OCT and flow velocities to accurately predict hyperemic pressure gradients.

    PubMed

    Kousera, C A; Nijjer, S; Torii, R; Petraco, R; Sen, S; Foin, N; Hughes, A D; Francis, D P P; Xu, X Y; Davies, J E

    2014-06-01

    Computational fluid dynamics (CFD) is increasingly being developed for the diagnostics of arterial diseases. Imaging methods such as computed tomography (CT) and angiography are commonly used. However, these have limited spatial resolution and are subject to movement artifact. This study developed a new approach to generate CFD models by combining high-fidelity, patient-specific coronary anatomy models derived from optical coherence tomography (OCT) imaging with patient-specific pressure and velocity phasic data. Additionally, we used a new technique which does not require the catheter to be used to determine the centerline of the vessel. The CFD data were then compared with invasively measured pressure and velocity. Angiography imaging data of 21 vessels collected from 19 patients were fused with OCT visualizations of the same vessels using an algorithm that produces reconstructions inheriting the in-plane (10 μm) and longitudinal (0.2 mm) resolution of OCT. Proximal pressure and distal velocity waveforms ensemble averaged from invasively measured data were used as inlet and outlet boundary conditions, respectively, in CFD simulations. The resulting distal pressure waveform was compared against the measured waveform to test the model. The results followed the shape of the measured waveforms closely (cross-correlation coefficient = 0.898 ± 0.005, ), indicating realistic modeling of flow resistance, the mean of differences between measured and simulated results was -3. 5 mmHg, standard deviation of differences (SDD) = 8.2 mmHg over the cycle and -9.8 mmHg, SDD = 16.4 mmHg at peak flow. Models incorporating phasic velocity in patient-specific models of coronary anatomy derived from high-resolution OCT images show a good correlation with the measured pressure waveforms in all cases, indicating that the model results may be an accurate representation of the measured flow conditions. PMID:24845301

  12. ATAD2 Overexpression Identifies Colorectal Cancer Patients with Poor Prognosis and Drives Proliferation of Cancer Cells

    PubMed Central

    Luo, Yang; Ye, Guang-Yao; Qin, Shao-Lan; Yu, Min-Hao; Mu, Yi-Fei; Zhong, Ming

    2015-01-01

    ATPase family AAA domain-containing 2 (ATAD2) has been identified as a critical modulator involved in cell proliferation and invasion. The purpose of this study was to explore the expression of ATAD2 in CRC tissues as well as its relationship with degree of malignancy. Data containing three independent investigations from Oncomine database demonstrated that ATAD2 is overexpressed in CRC compared with normal tissue, and similar result was also found in 32 pairs of CRC tissues by qPCR. The protein expression of ATAD2 was examined in six CRC cell lines and 300 CRC specimens. The results showed that high expression of ATAD2 was significantly correlated with tumor size (P < 0.001), serum CEA (P = 0.012), lymph node metastasis (P = 0.018), liver metastasis (P = 0.025), and clinical stage (P = 0.004). Kaplan-Meier method suggested that higher ATAD2 protein expression significantly associated with the overall survival (OS) of CRC patients (P < 0.001) and was an independent predictor of poor OS. Functional studies showed that suppression of ATAD2 expression with siRNA could significantly inhibit the growth in SW480 and HCT116 cells. These results indicated that ATAD2 could serve as a prognostic marker and a therapeutic target for CRC. PMID:26697062

  13. 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. PMID:25034911

  14. Metabolomics Identifies Biomarker Pattern for Early Diagnosis of Hepatocellular Carcinoma: from Diethylnitrosamine Treated Rats to Patients

    PubMed Central

    Zeng, Jun; Huang, Xin; Zhou, Lina; Tan, Yexiong; Hu, Chunxiu; Wang, Xiaomei; Niu, Junqi; Wang, Hongyang; Lin, Xiaohui; Yin, Peiyuan

    2015-01-01

    Early diagnosis of hepatocellular carcinoma (HCC) remains challenging to date. Characteristic metabolic deregulations of HCC may enable novel biomarkers discovery for early diagnosis. A capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics approach was performed to discover and validate potential biomarkers for HCC from the diethylnitrosamine-induced rat hepatocarcinogenesis model to human subjects. Time series sera from the animal model were evaluated using multivariate and univariate analyses to reveal dynamic metabolic changes. Two independent human cohorts (populations I and II) containing 122 human serum specimens were enrolled for validations. A novel biomarker pattern of ratio creatine/betaine which reflects the balance of methylation was identified. This biomarker pattern achieved effective classification of pre-HCC and HCC stages in animal model. It was still effective in the diagnosis of HCC from high-risk patients with cirrhotic nodules, achieving AUC values of 0.865 and 0.905 for two validation cohorts, respectively. The diagnosis of small HCC from cirrhosis with an AUC of 0.928 highlighted the potential for early diagnosis. This ratio biomarker can also improve the diagnostic performance of α-fetoprotein (AFP). This study demonstrates the efficacy of present strategy for biomarker discovery, and the potential of metabolomics approach to provide novel insights for disease study. PMID:26526930

  15. Functional Study of NIPA2 Mutations Identified from the Patients with Childhood Absence Epilepsy

    PubMed Central

    Xie, Han; Zhang, Yuehua; Zhang, Pingping; Wang, Jingmin; Wu, Ye; Wu, Xiru; Netoff, Theoden; Jiang, Yuwu

    2014-01-01

    Recently many genetic mutations that are associated with epilepsy have been identified. The protein NIPA2 (non-imprinted in Prader-Willi/Angelman syndrome region protein 2) is a highly selective magnesium transporter encoded by the gene NIPA2 in which we have found three mutations (p.I178F, p.N244S and p.N334_E335insD) within a population of patients with childhood absence epilepsy (CAE). In this study, immunofluorescence labeling, inductively coupled plasma-optical emission spectroscopy (ICP-OES), MTT metabolic rate detection and computational modeling were utilized to elucidate how these mutations result in CAE. We found in cultured neurons that NIPA2 (wild-type) proteins were localized to the cell periphery, whereas mutant proteins were not effectively trafficked to the cell membrane. Furthermore, we found a decrease in intracellular magnesium concentration in the neurons transfected with mutant NIPA2, but no effect on the survival of neurons. To understand how low intracellular magnesium resulted in hyperexcitability, we built and analyzed a computational model to simulate the effects of mutations. The model suggested that lower intracellular magnesium concentration enhanced synaptic N-methyl-D-aspartate receptor (NMDAR) currents. This study primarily reveals that a selective magnesium transporter NIPA2 may play a role in the pathogenesis of CAE. PMID:25347071

  16. Optimized Metabolomic Approach to Identify Uremic Solutes in Plasma of Stage 3–4 Chronic Kidney Disease Patients

    PubMed Central

    Mutsaers, Henricus A. M.; Engelke, Udo F. H.; Wilmer, Martijn J. G.; Wetzels, Jack F. M.; Wevers, Ron A.; van den Heuvel, Lambertus P.; Hoenderop, Joost G.; Masereeuw, Rosalinde

    2013-01-01

    Background Chronic kidney disease (CKD) is characterized by the progressive accumulation of various potential toxic solutes. Furthermore, uremic plasma is a complex mixture hampering accurate determination of uremic toxin levels and the identification of novel uremic solutes. Methods In this study, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy, following three distinct deproteinization strategies, to determine differences in the plasma metabolic status of stage 3–4 CKD patients and healthy controls. Moreover, the human renal proximal tubule cell line (ciPTEC) was used to study the influence of newly indentified uremic solutes on renal phenotype and functionality. Results Protein removal via ultrafiltration and acetonitrile precipitation are complementary techniques and both are required to obtain a clear metabolome profile. This new approach, revealed that a total of 14 metabolites were elevated in uremic plasma. In addition to confirming the retention of several previously identified uremic toxins, including p-cresyl sulphate, two novel uremic retentions solutes were detected, namely dimethyl sulphone (DMSO2) and 2-hydroxyisobutyric acid (2-HIBA). Our results show that these metabolites accumulate in non-dialysis CKD patients from 9±7 µM (control) to 51±29 µM and from 7 (0–9) µM (control) to 32±15 µM, respectively. Furthermore, exposure of ciPTEC to clinically relevant concentrations of both solutes resulted in an increased protein expression of the mesenchymal marker vimentin with more than 10% (p<0.05). Moreover, the loss of epithelial characteristics significantly correlated with a loss of glucuronidation activity (Pearson r = −0.63; p<0.05). In addition, both solutes did not affect cell viability nor mitochondrial activity. Conclusions This study demonstrates the importance of sample preparation techniques in the identification of uremic retention solutes using 1H-NMR spectroscopy, and provide insight into the negative impact of

  17. Functional and transport analyses of CLCN5 genetic changes identified in Dent disease patients.

    PubMed

    Tang, Xiaojing; Brown, Matthew R; Cogal, Andrea G; Gauvin, Daniel; Harris, Peter C; Lieske, John C; Romero, Michael F; Chang, Min-Hwang

    2016-04-01

    Dent disease type 1, an X-linked inherited kidney disease is caused by mutations in electrogenic Cl(-)/H(+) exchanger, ClC-5. We functionally studied the most frequent mutation (S244L) and two mutations recently identified in RKSC patients, Q629X and R345W. We also studied T657S, which has a high minor-allele frequency (0.23%) in the African-American population, was published previously as pathogenic to cause Dent disease. The transport properties of CLC-5 were electrophysiologically characterized. WT and ClC-5 mutant currents were inhibited by pH 5.5, but not affected by an alkaline extracellular solution (pH 8.5). The T657S and R345W mutations showed the same anion selectivity sequence as WT ClC-5 (SCN(-)>NO3(-)≈Cl(-)>Br(-)>I(-)). However, the S244L and Q629X mutations abolished this anion conductance sequence. Cell surface CLC-5 expression was quantified using extracellular HA-tagged CLC-5 and a chemiluminescent immunoassay. Cellular localization of eGFP-tagged CLC-5 proteins was also examined in HEK293 cells with organelle-specific fluorescent probes. Functional defects of R345W and Q629X mutations were caused by the trafficking of the protein to the plasma membrane since proteins were mostly retained in the endoplasmic reticulum, and mutations showed positive correlations between surface expression and transport function. In contrast, although the S244L transport function was significantly lower than WT, cell surface, early endosome, and endoplasmic reticulum expression was equal to that of WT CLC-5. Function and trafficking of T657S was equivalent to the WT CLC-5 suggesting this is a benign variant rather than pathogenic. These studies demonstrate the useful information that can be gained by detailed functional studies of mutations predicted to be pathogenic. PMID:27117801

  18. The Short Physical Performance Battery is a discriminative tool for identifying patients with COPD at risk of disability

    PubMed Central

    Bernabeu-Mora, Roberto; Medina-Mirapeix, Françesc; Llamazares-Herrán, Eduardo; García-Guillamón, Gloria; Giménez-Giménez, Luz María; Sánchez-Nieto, Juan Miguel

    2015-01-01

    Background Limited mobility is a risk factor for developing chronic obstructive pulmonary disease (COPD)-related disabilities. Little is known about the validity of the Short Physical Performance Battery (SPPB) for identifying mobility limitations in patients with COPD. Objective To determine the clinical validity of the SPPB summary score and its three components (standing balance, 4-meter gait speed, and five-repetition sit-to-stand) for identifying mobility limitations in patients with COPD. Methods This cross-sectional study included 137 patients with COPD, recruited from a hospital in Spain. Muscle strength tests and SPPB were measured; then, patients were surveyed for self-reported mobility limitations. The validity of SPPB scores was analyzed by developing receiver operating characteristic curves to analyze the sensitivity and specificity for identifying patients with mobility limitations; by examining group differences in SPPB scores across categories of mobility activities; and by correlating SPPB scores to strength tests. Results Only the SPPB summary score and the five-repetition sit-to-stand components showed good discriminative capabilities; both showed areas under the receiver operating characteristic curves greater than 0.7. Patients with limitations had significantly lower SPPB scores than patients without limitations in nine different mobility activities. SPPB scores were moderately correlated with the quadriceps test (r>0.40), and less correlated with the handgrip test (r<0.30), which reinforced convergent and divergent validities. A SPPB summary score cutoff of 10 provided the best accuracy for identifying mobility limitations. Conclusion This study provided evidence for the validity of the SPPB summary score and the five-repetition sit-to-stand test for assessing mobility in patients with COPD. These tests also showed potential as a screening test for identifying patients with COPD that have mobility limitations. PMID:26664110

  19. Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes

    PubMed Central

    Christodoulou, Katja; Wiskin, Anthony E; Gibson, Jane; Tapper, William; Willis, Claire; Afzal, Nadeem A; Upstill-Goddard, Rosanna; Holloway, John W; Simpson, Michael A; Beattie, R Mark; Collins, Andrew

    2013-01-01

    Background Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. Objective To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. Design DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. Results Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. Conclusion For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this

  20. Identifying patients with medically unexplained physical symptoms in electronic medical records in primary care: a validation study

    PubMed Central

    2014-01-01

    Background When medically unexplained physical symptoms (MUPS) become persistent, it may have major implications for the patient, the general practitioner (GP) and for society. Early identification of patients with MUPS in electronic medical records (EMRs) might contribute to prevention of persistent MUPS by creating awareness among GPs and providing an opportunity to start stepped care management. However, procedures for identification of patients with MUPS in EMRs are not well established yet. In this validation study we explore the test characteristics of an EMR screening method to identify patients with MUPS. Methods The EMR screening method consists of three steps. First, all patients ≥18 years were included when they had five or more contacts in the last 12 months. Second, patients with known chronic conditions were excluded. Finally, patients were included with a MUPS syndrome or when they had three or more complaints suggestive for MUPS. We compared the results of the EMR screening method with scores on the Patient Health Questionnaire-15 (PHQ-15), which we used as reference test. We calculated test characteristics for various cut-off points. Results From the 1223 patients in our dataset who completed the PHQ-15, 609 (49/8%) scored ≥5 on the PHQ-15. The EMR screening method detected 131/1223 (10.7%) as patients with MUPS. Of those, 102 (77.9%) scored ≥5 on the PHQ-15 and 53 (40.5%) scored ≥10. When compared with the PHQ-15 cut-off point ≥10, sensitivity and specificity were 0.30 and 0.93 and positive and negative predictive values were 0.40 and 0.89, respectively. Conclusions The EMR screening method to identify patients with MUPS has a high specificity. However, many potential MUPS patients will be missed. Before using this method as a screening instrument for selecting patients who might benefit from structured care, its sensitivity needs to be improved while maintaining its specificity. PMID:24903850

  1. Implementation of an Early Warning Scoring System to Identify Patients With Cancer at Risk for Deterioration.

    PubMed

    Olsen, MiKaela; Mooney, Kathy; Evans, Ellen

    2016-08-01

    Early warning scoring systems are tools for nurses to help monitor their patients and improve how quickly a patient experiencing a sudden decline receives clinical care. Nurse leaders and frontline staff at a major academic medical center implemented a new early warning system that gives clear guidelines to nurses, nursing assistants, and other clinicians about vital-sign parameters and changes in patients' mental status. 
. PMID:27441509

  2. Disease-Targeted Sequencing of Ion Channel Genes identifies de novo mutations in Patients with Non-Familial Brugada Syndrome

    PubMed Central

    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

    2014-01-01

    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. PMID:25339316

  3. 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. PMID:27332377

  4. 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

  5. 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. PMID:23295735

  6. 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.

  7. Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios.

    PubMed

    Herzog, Katharina; Pras-Raves, Mia L; Vervaart, Martin A T; Luyf, Angela C M; van Kampen, Antoine H C; Wanders, Ronald J A; Waterham, Hans R; Vaz, Frédéric M

    2016-08-01

    Peroxisomes are subcellular organelles involved in various metabolic processes, including fatty acid and phospholipid homeostasis. The Zellweger spectrum disorders (ZSDs) represent a group of diseases caused by a defect in the biogenesis of peroxisomes. Accordingly, cells from ZSD patients are expected to have an altered composition of fatty acids and phospholipids. Using an LC/MS-based lipidomics approach, we show that the phospholipid composition is characteristically altered in cultured primary skin fibroblasts from ZSD patients when compared with healthy controls. We observed a marked overall increase of phospholipid species containing very long-chain fatty acids, and a decrease of phospholipid species with shorter fatty acid species in ZSD patient fibroblasts. In addition, we detected a distinct phosphatidylcholine profile in ZSD patients with a severe and mild phenotype when compared with control cells. Based on our data, we present a set of specific phospholipid ratios for fibroblasts that clearly discriminate between mild and severe ZSD patients, and those from healthy controls. Our findings will aid in the diagnosis and prognosis of ZSD patients, including an increasing number of mild patients in whom hardly any abnormalities are observed in biochemical parameters commonly used for diagnosis. PMID:27284103

  8. 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. PMID:24621546

  9. Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics

    PubMed Central

    2011-01-01

    Background One of the challenges in the interpretation of studies showing associations between environmental and genotypic data with disease outcomes such as neovascular age-related macular degeneration (AMD) is understanding the phenotypic heterogeneity within a patient population with regard to any risk factor associated with the condition. This is critical when considering the potential therapeutic response of patients to any drug developed to treat the condition. In the present study, we identify patient subtypes or clusters which could represent several different targets for treatment development, based on genetic pathways in AMD and cardiovascular pathology. Methods We identified a sample of patients with neovascular AMD, that in previous studies had been shown to be at elevated risk for the disease through environmental factors such as cigarette smoking and genetic variants including the complement factor H gene (CFH) on chromosome 1q25 and variants in the ARMS2/HtrA serine peptidase 1 (HTRA1) gene(s) on chromosome 10q26. We conducted a multivariate segmentation analysis of 253 of these patients utilizing available epidemiologic and genetic data. Results In a multivariate model, cigarette smoking failed to differentiate subtypes of patients. However, four meaningfully distinct clusters of patients were identified that were most strongly differentiated by their cardiovascular health status (histories of hypercholesterolemia and hypertension), and the alleles of ARMS2/HTRA1 rs1049331. Conclusions These results have significant personalized medicine implications for drug developers attempting to determine the effective size of the treatable neovascular AMD population. Patient subtypes or clusters may represent different targets for therapeutic development based on genetic pathways in AMD and cardiovascular pathology, and treatments developed that may elevate CV risk, may be ill advised for certain of the clusters identified. PMID:21682878

  10. Proactive Risk Assessment for Ebola-Infected Patients: A Systematic Approach to Identifying and Minimizing Risk to Healthcare Personnel.

    PubMed

    Fernandez, Rosemarie; Mitchell, Steven; Ehrmantraut, Ross; Meschke, John Scott; Simcox, Nancy J; Wolz, Sarah A; Parker, Sarah Henrickson

    2016-07-01

    Performing patient care while wearing high-level personal protective equipment presents risks to healthcare providers. Our failure mode effects analysis identified 81 overall risks associated with providing hygienic care and linen change to a patient with continuous watery stool. Implementation of checklists and scheduled pauses could potentially mitigate 76.5% of all risks. Infect Control Hosp Epidemiol 2016;37:867-871. PMID:27226216

  11. Identifying Drivers of Overall Satisfaction in Patients Receiving HIV Primary Care: A Cross-Sectional Study

    PubMed Central

    Dang, Bich N.; Westbrook, Robert A.; Rodriguez-Barradas, Maria C.; Giordano, Thomas P.

    2012-01-01

    Objective This study seeks to understand the drivers of overall patient satisfaction in a predominantly low-income, ethnic-minority population of HIV primary care patients. The study’s primary aims were to determine 1) the component experiences which contribute to patients’ evaluations of their overall satisfaction with care received, and 2) the relative contribution of each component experience in explaining patients’ evaluation of overall satisfaction. Methods We conducted a cross-sectional study of 489 adult patients receiving HIV primary care at two clinics in Houston, Texas, from January 13–April 21, 2011. The participation rate among eligible patients was 94%. The survey included 15 questions about various components of the care experience, 4 questions about the provider experience and 3 questions about overall care. To ensure that the survey was appropriately tailored to our clinic population and the list of component experiences reflected all aspects of the care experience salient to patients, we conducted in-depth interviews with key providers and clinic staff and pre-tested the survey instrument with patients. Results Patients’ evaluation of their provider correlated the strongest with their overall satisfaction (standardized β = 0.445, p<0.001) and accounted for almost half of the explained variance. Access and availability, like clinic hours and ease of calling the clinic, also correlated with overall satisfaction, but less strongly. Wait time and parking, despite receiving low patient ratings, did not correlate with overall satisfaction. Conclusions The patient-provider relationship far exceeds other component experiences of care in its association with overall satisfaction. Our study suggests that interventions to improve overall patient satisfaction should focus on improving patients’ evaluation of their provider. PMID:22912770

  12. Single nucleotide variations in CLCN6 identified in patients with benign partial epilepsies in infancy and/or febrile seizures.

    PubMed

    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

  13. 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

  14. 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. PMID:24782504

  15. 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.

  16. Tough-skinned kids: identifying psychosocial effects of psoriasis and helping pediatric patients and families cope.

    PubMed

    Lin, Virginia W

    2012-10-01

    Outward appearance is exquisitely and undeniably tied to self-perception. Pediatric patients with psoriasis face the challenge of coping with psychosocial issues because of the visibility of their skin lesions. The burden of psoriasis also affects the quality of life of family members. This article discusses pediatric psoriasis, current literature on psychosocial impact, role of the nurse to help patients and families cope, and recommendations for further research. Through clinical intervention, patient education, and referral to resources, the nurse can hope to relieve some stress and help the child, adolescent, and family maintain their improved quality of life. PMID:22101138

  17. 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

  18. 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

    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 (-α(3.7)), 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 (α(codon 59)α/α(CS)α) 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 (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). 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

  19. 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

  20. Derivation and validation of a simple, accurate and robust prediction rule for risk of mortality in patients with Clostridium difficile infection

    PubMed Central

    2013-01-01

    Background Clostridium difficile infection poses a significant healthcare burden. However, the derivation of a simple, evidence based prediction rule to assist patient management has not yet been described. This study aimed to identify such a prediction rule to stratify hospital inpatients according to risk of all-cause mortality, at initial diagnosis of infection. Method Univariate, multivariate and decision tree procedures were used to deduce a prediction rule from over 186 variables; retrospectively collated from clinical data for 213 patients. The resulting prediction rule was validated on independent data from a cohort of 158 patients described by Bhangu et al. (Colorectal Disease, 12(3):241-246, 2010). Results Serum albumin levels (g/L) (P = 0.001), respiratory rate (resps /min) (P = 0.002), C-reactive protein (mg/L) (P = 0.034) and white cell count (mcL) (P = 0.049) were predictors of all-cause mortality. Threshold levels of serum albumin ≤ 24.5 g/L, C- reactive protein >228 mg/L, respiratory rate >17 resps/min and white cell count >12 × 103 mcL were associated with an increased risk of all-cause mortality. A simple four variable prediction rule was devised based on these threshold levels and when tested on the initial data, yield an area under the curve score of 0.754 (P < 0.001) using receiver operating characteristics. The prediction rule was then evaluated using independent data, and yield an area under the curve score of 0.653 (P = 0.001). Conclusions Four easily measurable clinical variables can be used to assess the risk of mortality of patients with Clostridium difficile infection and remains robust with respect to independent data. PMID:23849267

  1. 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. PMID:27561146

  2. 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

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

    PubMed

    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

  4. Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma.

    PubMed

    Wang, Liang; Wang, Hua; Xia, Zhong-Jun; Huang, Hui-Qiang; Jiang, Wen-Qi; Lin, Tong-Yu; Lu, Yue

    2015-10-01

    Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P = 0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P = 0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population. PMID:26082333

  5. AB031. Validation of claims approach to identify asthma and COPD overlap syndrome patients in the United States

    PubMed Central

    Ding, Bo; De Pietro, Michael; Wu, Bingcao; Tunceli, Ozgur; Turner, Ralph

    2016-01-01

    Background With the increasing recognition of asthma and chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and its significant disease and economic burden, knowledge about real-world patient characteristics and how they are treated is needed to aid in better understanding this phenotype. However, ACOS patient identification is challenging. Currently, there is no validated claims-based ACOS patient selection algorithm available to assist this type of research. To assess the validity of a retrospective claims-based algorithm to identify high likelihood ACOS patients using patient medical records as the criterion. Methods Patients were identified from the US based HealthCore Integrated Research Database (HIRD) between January 1, 2006 and October 31, 2014. A claims-based algorithm to identify high likelihood ACOS patients was based on the following inclusion criteria: age ≥40 years, ≥2 ICD-9 diagnoses (≥30 days apart) for asthma, (ICD-9 CM: 493.xx), ≥2 diagnoses (≥30 days apart) for COPD (ICD-9 CM: 491.xx, 492.xx, and 496.xx), ≥2 ICD-9 procedure, Current Procedural Terminology (CPT), or Healthcare Common Procedure Coding System (HCPCS) codes (≥30 days apart) for COPD-related procedures, ≥3 prescription fills (≥30 days apart) for asthma/COPD medication, and ≥2 CPT codes for spirometry test. Patients were indexed on the earliest date when all of the inclusion criteria were met. Patients diagnosed with cancer (ICD-9 CM: 140.xx–209.3x, 230.xx–234.xx) during the 12-month pre-index period were excluded. Outpatient medical records closest to (before or after) the index date were abstracted. Based on the chart review, at least 2 features (positive history of allergic rhinitis, chronic sinusitis, eczema, positive skin test to environmental allergens or desensitization to environmental allergens, diagnosis of asthma or past medical history for asthma before 40 years of age, or family history of asthma) were needed to confirm the asthma

  6. A cross-sectional study to identify organisational processes associated with nurse-reported quality and patient safety

    PubMed Central

    Tvedt, Christine; Sjetne, Ingeborg Strømseng; Helgeland, Jon; Bukholm, Geir

    2012-01-01

    Objectives The purpose of this study was to identify organisational processes and structures that are associated with nurse-reported patient safety and quality of nursing. Design This is an observational cross-sectional study using survey methods. Setting Respondents from 31 Norwegian hospitals with more than 85 beds were included in the survey. Participants All registered nurses working in direct patient care in a position of 20% or more were invited to answer the survey. In this study, 3618 nurses from surgical and medical wards responded (response rate 58.9). Nurses' practice environment was defined as organisational processes and measured by the Nursing Work Index Revised and items from Hospital Survey on Patient Safety Culture. Outcome measures Nurses' assessments of patient safety, quality of nursing, confidence in how their patients manage after discharge and frequency of adverse events were used as outcome measures. Results Quality system, nurse–physician relation, patient safety management and staff adequacy were process measures associated with nurse-reported work-related and patient-related outcomes, but we found no associations with nurse participation, education and career and ward leadership. Most organisational structures were non-significant in the multilevel model except for nurses’ affiliations to medical department and hospital type. Conclusions Organisational structures may have minor impact on how nurses perceive work-related and patient-related outcomes, but the findings in this study indicate that there is a considerable potential to address organisational design in improvement of patient safety and quality of care. PMID:23263021

  7. Radionuclide methods of identifying patients who may require coronary artery bypass surgery

    SciTech Connect

    Beller, G.A.; Gibson, R.S.; Watson, D.D.

    1985-12-01

    Myocardial thallium-201 (/sup 201/Tl) scintigraphy or radionuclide angiography performed in conjunction with exercise stress testing can provide clinically useful information regarding the functional significance of underlying coronary artery stenoses in patients with known or suspected coronary artery disease. Knowledge of type, location, and extent of myocardial /sup 201/Tl perfusion abnormalities or the severity of exercise-induced global and regional dysfunction has prognostic value. Risk stratification can be undertaken with either radionuclide technique by consideration of the magnitude of the ischemic response and may assist in the selection of patients for coronary artery bypass graft surgery (CABG). In patients with coronary artery disease, delayed /sup 201/Tl redistribution observed on exercise or dipyridamole /sup 201/Tl scintigraphy, particularly when present in multiple vascular regions and associated with increased lung /sup 201/Tl uptake, has been shown to be predictive of an adverse outcome, whereas patients with chest pain and a normal exercise /sup 201/Tl scintigram have a good prognosis with medical treatment. Similarly, a marked fall in the radionuclide ejection fraction from rest to exercise has been found to correlate with high-risk anatomic disease. Another important application of radionuclide imaging in patients being considered for CABG (particularly those with a depressed resting left ventricular ejection fraction) is the determination of myocardial viability and potential for improved blood flow and enhanced regional function after revascularization. 69 references.

  8. Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.

    PubMed

    Nitta, Hirohisa; Unoki, Motoko; Ichiyanagi, Kenji; Kosho, Tomoki; Shigemura, Tomonari; Takahashi, Hiroshi; Velasco, Guillaume; Francastel, Claire; Picard, Capucine; Kubota, Takeo; Sasaki, Hiroyuki

    2013-07-01

    Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, α-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation. PMID:23739126

  9. 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.

  10. 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. PMID:11154961

  11. [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. PMID:1963992

  12. Orolingual angioedema to alteplase. Identify, counsel and monitor at risk patients.

    PubMed

    Timmis, Christopher; Epstein, Elliot; Salim, Mohmad

    2016-01-01

    Orolingual angioedema (OLA) is a known complication of intravenous alteplase used to treat ischaemic stroke. The incidence may be as high as 5.1%. ACE inhibitors are thought to increase the risk of developing this potentially life-threatening complication. This case report demonstrates how we may improve in the identification of risk factors in the history; the counselling of patients appropriately; in seeking alternative therapies such as mechanical thrombectomy; and in the monitoring of patients for signs of OLA once alteplase has been given. PMID:27591036

  13. Identifying mental health symptoms in children and youth in residential and in-patient care settings.

    PubMed

    Stewart, Shannon L; Hirdes, John P

    2015-07-01

    This study demonstrates the use of the interRAI assessment instruments to examine mental health symptoms in children and adults within residential and in-patient care settings. Regardless of service setting, children exhibited more harm to self and others than adults. Children in adult in-patient beds were more likely to exhibit suicide and self-harm and less likely to exhibit harm to others compared to children in child-specific service settings. Implications related to service system improvements are discussed. PMID:26015486

  14. [In a medical setting, why and how can the doctor identify the patient as a victim of abuse].

    PubMed

    Gauthier, C

    2011-01-01

    People who were victims of childhood abuse (sexual, emotional or physical), later on will develop psychosomatic illnesses and psychological problems. These health problems, sad consequences of past abuse, will bring them to consult a physician at one point or another. But, because these patients often do not talk about the ancient trauma, the physician is unaware of this past abuse and only treats the illness' symptoms. Abused people will also develop behavioral problems which put them repeatedly back into the position of victim, without realizing why. If this dysfunctional behavior is not identified as the result of trauma, these multi-abused patients will go from bad to worse, repeating in an endless cycle their role as victim. If the physician is able to identify this typical replay of victimization, the patient can be helped to become aware of and to avoid compulsive self-abusive behaviors which are discussed in the following article. PMID:21942076

  15. Blood DNA methylation markers in potentially identified Chinese patients with hepatocellular carcinoma.

    PubMed

    Liu, Zongying; Yan, Haixiu; Zhang, Jinshu

    2016-07-01

    To determine whether blood DNA methylation is associated with hepatocellular carcinoma (HCC) for Chinese patients, we used genome-wide DNA methylation detection to access the blood samples of Chinese patients by Illumina Human methylation 450K arrays. Sixty potentially gene locis which had different methylated levels significantly among tumor and adjacent normal tissues would be tested in this study. A previous study was conducted in China communities and followed with 7 years. The DNA from white blood cells (WBC) from 192 patients with HCC and 215 matched controls were assayed in this study. The χ2 test was used to measure data to categorize variables and t -test was used to evaluate the different characteristics among groups. Besides, odds ratios (OR) and 95%CI was calculated for matching factors by conditional logistic regression models. We found that high methylation in WNK2 was related to increased risk of HCC, and high methylation in TPO were related to decreased risk of HCC. In our multivariable conditional logistic regression models, these results all exist. Those findings support the methylated changes of WNK2 and TPO may become a new detection index for HCC patients in clinical laboratory. However, the results should be replicated in additional prospective studies with lager samples. PMID:27592479

  16. 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. PMID:26546315

  17. 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

  18. 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

  19. Clinical next generation sequencing of pediatric-type malignancies in adult patients identifies novel somatic aberrations

    PubMed Central

    Silva, Jorge Galvez; Corrales-Medina, Fernando F.; Maher, Ossama M.; Tannir, Nizar; Huh, Winston W.; Rytting, Michael E.; Subbiah, Vivek

    2015-01-01

    Pediatric malignancies in adults, in contrast to the same diseases in children are clinically more aggressive, resistant to chemotherapeutics, and carry a higher risk of relapse. Molecular profiling of tumor sample using next generation sequencing (NGS) has recently become clinically available. We report the results of targeted exome sequencing of six adult patients with pediatric-type malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and desmoplastic small round cell tumor (n=1) with a median age of 28.8 years. Detection of druggable somatic aberrations in tumors is feasible. However, identification of actionable target therapies in these rare adult patients with pediatric-type malignancies is challenging. Continuous efforts to establish a rare disease registry are warranted. PMID:25859559

  20. Clinical next generation sequencing of pediatric-type malignancies in adult patients identifies novel somatic aberrations.

    PubMed

    Silva, Jorge Galvez; Corrales-Medina, Fernando F; Maher, Ossama M; Tannir, Nizar; Huh, Winston W; Rytting, Michael E; Subbiah, Vivek

    2015-01-01

    Pediatric malignancies in adults, in contrast to the same diseases in children are clinically more aggressive, resistant to chemotherapeutics, and carry a higher risk of relapse. Molecular profiling of tumor sample using next generation sequencing (NGS) has recently become clinically available. We report the results of targeted exome sequencing of six adult patients with pediatric-type malignancies : Wilms tumor(n=2), medulloblastoma(n=2), Ewing's sarcoma( n=1) and desmoplastic small round cell tumor (n=1) with a median age of 28.8 years. Detection of druggable somatic aberrations in tumors is feasible. However, identification of actionable target therapies in these rare adult patients with pediatric-type malignancies is challenging. Continuous efforts to establish a rare disease registry are warranted. PMID:25859559

  1. Identifying critically ill patients with acute kidney injury for whom renal replacement therapy is inappropriate: an exercise in futility?

    PubMed Central

    Gabbay, Ezra; Meyer, Klemens B.

    2009-01-01

    Clinicians treating critically ill patients must consider the possibility that painful and expensive aggressive treatments might confer negligible benefit. Such treatments are often described as futile or inappropriate. We discuss the problem of deciding whether to initiate renal replacement therapy (RRT) for critically ill patients with acute kidney injury (AKI) in the context of the debate surrounding medical futility. The main problems in deciding when such treatment would be futile are that the concept itself is controversial and eludes quantitative definition, that available outcome data do not allow confident identification of patients who will not benefit from treatment and that the decision on RRT in a critically ill patient with AKI is qualitatively different from decisions on other modalities of intensive care and resuscitation, as well as from decisions on dialysis for chronic kidney disease. Despite these difficulties, nephrologists need to identify circumstances in which continued aggressive care would be futile before proceeding to initiate RRT. PMID:25949304

  2. [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. PMID:1965370

  3. Identifying patients infected with hepatitis B virus in sub-Saharan Africa: potential for misclassification.

    PubMed

    Boyd, Anders; Maylin, Sarah; Moh, Raoul; Gabillard, Delphine; Menan, Hervé; Mahjoub, Nadia; Danel, Christine; Anglaret, Xavier; Eholié, Serge Paul; Girard, Pierre-Marie; Zoulim, Fabien; Delaugerre, Constance; Lacombe, Karine

    2015-11-01

    Most research in sub-Saharan Africa establishes hepatitis B infection via one-time hepatitis B surface antigen (HBsAg) testing. Of 237 HIV-infected patients from two clinical trials testing HBsAg positive (MiniVidas®), 206 (86.9%) had validated serological tests using another assay (Architect). Discrepancies could be due to inactive infection, highlighting the importance of assessing hepatitis B virus infection phase. PMID:26283522

  4. An Adaptive Approach for Identifying Cocaine Dependent Patients Who Benefit from Extended Continuing Care

    PubMed Central

    McKay, James R.; Van Horn, Deborah; Lynch, Kevin G.; Ivey, Megan; Cary, Mark S.; Drapkin, Michelle; Coviello, Donna M.; Plebani, Jennifer G.

    2014-01-01

    Objective Study tested whether cocaine dependent patients using cocaine or alcohol at intake or in the first few weeks of intensive outpatient treatment would benefit more from extended continuing care than patients abstinent during this period. The effect of incentives for continuing care attendance was also examined. Methods Participants (N=321) were randomized to: treatment as usual (TAU), TAU and Telephone Monitoring and Counseling (TMC), or TAU and TMC plus incentives (TMC+). The primary outcomes were: (1) abstinence from all drugs and heavy alcohol use, and (2) cocaine urine toxicology. Follow-ups were at 3, 6, 9, 12, 18, and 24 months. Results Cocaine and alcohol use at intake or early in treatment predicted worse outcomes on both measures (ps≤ .0002). Significant effects favoring TMC over TAU on the abstinence composite were obtained in participants who used cocaine (OR=1.95 [1.02, 3.73]) or alcohol (OR=2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using cocaine during that period (OR= 0.55 [0.31, 0.95]). Conversely, there were no treatment effects in participants abstinent at baseline, and no overall treatment main effects. Incentives almost doubled the number of continuing care sessions received, but did not further improve outcomes. Conclusion An adaptive approach for cocaine dependence in which extended continuing care is provided only to patients who are using cocaine or alcohol at intake or early in treatment improves outcomes in this group while reducing burden and costs in lower risk patients. PMID:24041231

  5. Development of the A-DIVA Scale: A Clinical Predictive Scale to Identify Difficult Intravenous Access in Adult Patients Based on Clinical Observations.

    PubMed

    van Loon, Fredericus H J; Puijn, Lisette A P M; Houterman, Saskia; Bouwman, Arthur R A

    2016-04-01

    Placement of a peripheral intravenous catheter is a routine procedure in clinical practice, but failure of intravenous cannulation regularly occurs. An accurate and reliable predictive scale for difficult venous access creates the possibility to use other techniques in an earlier time frame. We aimed to develop a predictive scale to identify adult patients with a difficult intravenous access prospectively: the A-DIVA scale. This prospective, observational, cross-sectional cohort study was conducted between January 2014 and January 2015, and performed at the department of anesthesiology of the Catharina Hospital (Eindhoven, The Netherlands). Patients 18 years or older were eligible if scheduled for any surgical procedure, regardless ASA classification, demographics, and medical history. Experienced and certified anesthesiologists and nurse anesthetists routinely obtained peripheral intravenous access. Cannulation was performed regarding standards for care. A failed peripheral intravenous cannulation on the first attempt was the outcome of interest. A population-based sample of 1063 patients was included. Failure of intravenous cannulation was observed in 182/1063 patients (17%). Five variables were associated with a failed first attempt of peripheral intravenous cannulation: palpability of the target vein (OR = 4.94, 95% CI [2.85-8.56]; P < 0.001), visibility of the target vein (OR = 3.63, 95% CI [2.09-6.32]; P < 0.001), a history of difficult peripheral intravenous cannulation (OR = 3.86, 95% CI [2.39-6.25]; P < 0.001), an unplanned indication for surgery (OR = 4.86, 95% CI [2.92-8.07]; P < 0.001), and the vein diameter of at most 2 millimeters (OR = 3.37, 95% CI [2.12-5.36]; P < 0.001). The scoring system was applied in 3 risk groups: 36/788 patients (5%) suffered from a failed first attempt in the low-risk group (A-DIVA score 0 or 1), whereas the medium (A-DIVA score 2 or 3) and high-risk group (A-DIVA score 4 plus

  6. Whole exome sequencing identifies the first STRADA point mutation in a patient with polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE).

    PubMed

    Bi, Weimin; Glass, Ian A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Yang, Yaping; Sun, Angela

    2016-08-01

    Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is an ultra rare neurodevelopmental disorder characterized by severe, infantile-onset intractable epilepsy, neurocognitive delay, macrocephaly, and craniofacial dysmorphism. The molecular diagnosis of this condition has thus far only been made in 16 Old Order Mennonite patients carrying a homozygous 7 kb founder deletion of exons 9-13 of STRADA. We performed clinical whole exome sequencing (WES) on a 4-year-old Indian male with global developmental delay, history of failure to thrive, infantile spasms, repetitive behaviors, hypotonia, low muscle mass, marked joint laxity, and dysmorphic facial features including tall forehead, long face, arched eyebrows, small chin, wide mouth, and tented upper lip. A homozygous single nucleotide duplication, c.842dupA (p.D281fs), in exon 10 of STRADA was identified. Sanger sequencing confirmed the mutation in the individual and identified both parents as carriers. In light of the molecular discoveries, the patient's clinical phenotype was considered to be a good fit for PMSE. We identified for the first time a homozygous point mutation in STRADA causing PMSE. Additional bi-allelic mutations related to PMSE thus far have not been observed in Baylor ∼6,000 consecutive clinical WES cases, supporting the rarity of this disorder. Our findings may have treatment implications for the patient since previous studies have shown rapamycin as a potential therapeutic agent for the seizures and cognitive problems in PMSE patients. © 2016 Wiley Periodicals, Inc. PMID:27170158

  7. High-throughput RNAi screening of human kinases identifies predictors of clinical outcome in colorectal cancer patients treated with oxaliplatin

    PubMed Central

    Li, Ajian; Tang, Erjiang; Peng, Jian; Tang, Wenxian; Zhang, Yong; Lu, Liang; Xiao, Yihua; Wei, Qing; Yin, Lu; Li, Huaguang

    2015-01-01

    The purpose of this study is to identify protein kinase genes that modulate oxaliplatin cytotoxicity in vitro and evaluate the roles of these genes in predicting clinical outcomes in CRC patients receiving oxaliplatin-based adjuvant chemotherapy. A high-throughput RNAi screening targeting 626 human kinase genes was performed to identify kinase genes whose inhibition potentiates oxaliplatin sensitivity in CRC cells. The associations between copy numbers of the candidate genes and recurrence-free survival and overall survival were analyzed in 142 stage III CRC patients receiving first-line oxaliplatin-based adjuvant chemotherapy who were enrolled from two independent hospitals. HT-RNAi screening identified 40 kinase genes whose inhibition potentiated oxaliplatin cytotoxicity in DLD1 cells. The relative copy number (RCN) of MAP4K1 and CDKL4 were associated with increased risks of both recurrence and death. Moreover, significant genes-based risk score and the ratios of RCN of different genes can further categorize patients into subgroups with distinctly differing outcomes. The estimated AUC for the prediction models including clinical variables plus kinase biomarkers was 0.77 for the recurrence and 0.82 for the survival models. The copy numbers of MAP4K1 and CDKL4 can predict clinical outcomes in CRC patients treated with oxaliplatin-based chemotherapy. PMID:25904054

  8. Development and validation of an algorithm to identify patients newly diagnosed with HIV infection from electronic health records.

    PubMed

    Goetz, Matthew Bidwell; Hoang, Tuyen; Kan, Virginia L; Rimland, David; Rodriguez-Barradas, Maria

    2014-07-01

    An algorithm was developed that identifies patients with new diagnoses of HIV infection by the use of electronic health records. It was based on the sequence of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at four large urban Veterans Health Administration (VHA) facilities. Source data were obtained from the VHA National Corporate Data Warehouse. Chart review was done by a single trained abstractor to validate site-level data regarding new diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test within the VHA. Of these, 57% were determined to have prior knowledge of their HIV status from testing at non-VHA facilities. An algorithm based on the sequence and results of available laboratory tests and ICD-9-CM entries identified new HIV diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90%. There were no meaningful demographic or clinical differences between newly diagnosed patients who were correctly or incorrectly classified by the algorithm. We have validated a method to identify cases of new diagnosis of HIV infection in large administrative datasets. This method, which has a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90% can be used in analyses of the epidemiology of newly diagnosed HIV infection. PMID:24564256

  9. Functional variants of POC5 identified in patients with idiopathic scoliosis

    PubMed Central

    Patten, Shunmoogum A.; Margaritte-Jeannin, Patricia; Bernard, Jean-Claude; Alix, Eudeline; Labalme, Audrey; Besson, Alicia; Girard, Simon L.; Fendri, Khaled; Fraisse, Nicolas; Biot, Bernard; Poizat, Coline; Campan-Fournier, Amandine; Abelin-Genevois, Kariman; Cunin, Vincent; Zaouter, Charlotte; Liao, Meijiang; Lamy, Raphaelle; Lesca, Gaetan; Menassa, Rita; Marcaillou, Charles; Letexier, Melanie; Sanlaville, Damien; Berard, Jerome; Rouleau, Guy A.; Clerget-Darpoux, Françoise; Drapeau, Pierre; Moldovan, Florina; Edery, Patrick

    2015-01-01

    Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS. PMID:25642776

  10. Identifying and preventing medical errors in patients with limited English proficiency: key findings and tools for the field.

    PubMed

    Wasserman, Melanie; Renfrew, Megan R; Green, Alexander R; Lopez, Lenny; Tan-McGrory, Aswita; Brach, Cindy; Betancourt, Joseph R

    2014-01-01

    Since the 1999 Institute of Medicine (IOM) report To Err is Human, progress has been made in patient safety, but few efforts have focused on safety in patients with limited English proficiency (LEP). This article describes the development, content, and testing of two new evidence-based Agency for Healthcare Research and Quality (AHRQ) tools for LEP patient safety. In the content development phase, a comprehensive mixed-methods approach was used to identify common causes of errors for LEP patients, high-risk scenarios, and evidence-based strategies to address them. Based on our findings, Improving Patient Safety Systems for Limited English Proficient Patients: A Guide for Hospitals contains recommendations to improve detection and prevention of medical errors across diverse populations, and TeamSTEPPS Enhancing Safety for Patients with Limited English Proficiency Module trains staff to improve safety through team communication and incorporating interpreters in the care process. The Hospital Guide was validated with leaders in quality and safety at diverse hospitals, and the TeamSTEPPS LEP module was field-tested in varied settings within three hospitals. Both tools were found to be implementable, acceptable to their audiences, and conducive to learning. Further research on the impact of the combined use of the guide and module would shed light on their value as a multifaceted intervention. PMID:24629098

  11. An Alzheimer’s Disease-Derived Biomarker Signature Identifies Parkinson’s Disease Patients with Dementia

    PubMed Central

    Berlyand, Yosef; Weintraub, Daniel; Xie, Sharon X.; Mellis, Ian A.; Doshi, Jimit; Rick, Jacqueline; McBride, Jennifer; Davatzikos, Christos; Shaw, Leslie M.; Hurtig, Howard; Trojanowski, John Q.; Chen-Plotkin, Alice S.

    2016-01-01

    Biomarkers from multiple modalities have been shown to correlate with cognition in Parkinson’s disease (PD) and in Alzheimer’s disease (AD). However, the relationships of these markers with each other, and the use of multiple markers in concert to predict an outcome of interest, are areas that are much less explored. Our objectives in this study were (1) to evaluate relationships among 17 biomarkers previously reported to associate with cognition in PD or AD and (2) to test performance of a five-biomarker classifier trained to recognize AD in identifying PD with dementia (PDD). To do this, we evaluated a cross-sectional cohort of PD patients (n = 75) across a spectrum of cognitive abilities. All PD participants had 17 baseline biomarkers from clinical, genetic, biochemical, and imaging modalities measured, and correlations among biomarkers were assessed by Spearman’s rho and by hierarchical clustering. We found that internal correlation among all 17 candidate biomarkers was modest, showing a maximum pairwise correlation coefficient of 0.51. However, a five-marker subset panel derived from AD (CSF total tau, CSF phosphorylated tau, CSF amyloid beta 42, APOE genotype, and SPARE-AD imaging score) discriminated cognitively normal PD patients vs. PDD patients with 80% accuracy, when employed in a classifier originally trained to recognize AD. Thus, an AD-derived biomarker signature may identify PDD patients with moderately high accuracy, suggesting mechanisms shared with AD in some PDD patients. Based on five measures readily obtained during life, this AD-derived signature may prove useful in identifying PDD patients most likely to respond to AD-based crossover therapies. PMID:26812251

  12. ED-based screening programs for hepatitis C (HCV) highlight significant opportunity to identify patients, prevent downstream costs/complications.

    PubMed

    2014-01-01

    New data suggest there is a huge opportunity for EDs to identify patients with the hepatitis C virus (HCV) and link them into care before downstream complications lead to higher medical costs and adverse outcomes. Early results from a pilot study at the University of Alabama Medical Center in Birmingham show that at least 12% of the targeted baby boomer population being screened for HCV in the ED is testing positive for HCV, with confirmatory tests showing that about 9% of the screened population is infected with the disease. Both the Centers for Disease Control in Atlanta and the US Preventive Services Task Force recommend one-time HCV screening for patients who were born between 1945 and 1965. Public health experts say 75% of HCV infections occur in patients born during the baby boomer years, and that roughly half of them are unaware of their HCV status. Researchers at UAB report that so many patients are testing positive for HCV that demand for care can quickly overwhelm the health system if new primary care/specialty resources are not identified. Administrators of ED-based HCV screening programs in both Birmingham and Houston note that EDs with existing screening programs for HIV should have the easiest time implementing HCV screening. They also stress that patients are more accepting of HCV screening, and that the counseling process is easier. PMID:24432549

  13. 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. PMID:22570412

  14. Glycated hemoglobin screening identifies patients admitted for retreatment of tuberculosis at risk for diabetes in Tanzania

    PubMed Central

    Sariko, Margaretha L; Mpagama, Stellah G; Gratz, Jean; Kisonga, Riziki; Saidi, Queen; Kibiki, Gibson S; Heysell, Scott K

    2016-01-01

    Introduction World Health Organization recommendations of bidirectional screening for tuberculosis (TB) and diabetes have been met with varying levels of uptake by national TB programs in resource-limited settings. Methodology Kibong’oto Infectious Diseases Hospital (KIDH) is a referral hospital for TB from northern Tanzania, and the national referral hospital for multidrug-resistant (MDR)-TB. Glycated hemoglobin (HgbA1c) testing was done on patients admitted to KIDH for newly diagnosed TB, retreatment TB, and MDR-TB, to determine the point prevalence of diabetes (HgbA1c ≥ 6.5%) and prediabetes (HgbA1c 5.7%– 6.4%). Results Of 148 patients hospitalized at KIDH over a single week, 59 (38%) had no prior TB treatment, 22 (15%) were retreatment cases, and 69 (47%) had MDR-TB. Only 3 (2%) had a known history of diabetes. A total of 144 (97%) had successful screening, of which 110 (77%) had an HgbA1c ≤ 5.6%, 28 (19%) had ≥ 5.7 < 6.5, and 6 (4%) had ≥ 6.5. Comparing subjects with prediabetes or diabetes to those with normal A1c levels, retreatment patients were significantly more likely to have a A1c ≥ 5.7% (odds ratio: 3.2, 95% CI: 1.2–9.0; p = 0.02) compared to those without prior TB treatment. No retreatment case was a known diabetic, thus the number needed to screen to diagnose one new case of diabetes among retreatment cases was 11. Conclusions Diabetes prevalence by HgbA1c was less common than expected, but higher HgA1c values were significantly more frequent among retreatment cases, allowing for a rational, resource-conscious screening approach. PMID:27131008

  15. Sonic Hedgehog Mutations Identified in Holoprosencephaly Patients Can Act in a Dominant Negative Manner

    PubMed Central

    Singh, Samer; Tokhunts, Robert; Baubet, Valerie; Goetz, John A.; Huang, Zhen Jane; Schilling, Neal S.; Black, Kendall E.; MacKenzie, Todd A.; Dahmane, Nadia; Robbins, David J.

    2009-01-01

    Sonic Hedgehog (SHH) plays an important instructional role in vertebrate development, as exemplified by the numerous developmental disorders that occur when the SHH pathway is disrupted. Mutations in the SHH gene are the most common cause of sporadic and inherited Holoprosencephaly (HPE), a developmental disorder that is characterized by defective prosencephalon development. SHH HPE mutations provide a unique opportunity to better understand SHH biogenesis and signaling, and to decipher its role in the development of HPE. Here, we analyzed a panel of SHH HPE missense mutations that encode changes in the amino-terminal active domain of SHH. Our results show that SHH HPE mutations affect SHH biogenesis and signaling at multiple steps, which broadly results in low levels of protein expression, defective processing of SHH into its active form and protein with reduced activity. Additionally, we found that some inactive SHH proteins were able to modulate the activity of wt SHH in a dominant negative manner, both in vitro and in vivo. These findings show for the first time the susceptibility of SHH driven developmental processes to perturbations by low-activity forms of SHH. In conclusion, we demonstrate that SHH mutations found in HPE patients affect distinct steps of SHH biogenesis to attenuate SHH activity to different levels, and suggest that these variable levels of SHH activity might contribute to some of the phenotypic variation found in HPE patients. PMID:19057928

  16. Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia.

    PubMed

    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

    2013-03-01

    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

  17. MIR137 variants identified in psychiatric patients affect synaptogenesis and neuronal transmission gene sets.

    PubMed

    Strazisar, M; Cammaerts, S; van der Ven, K; Forero, D A; Lenaerts, A-S; Nordin, A; Almeida-Souza, L; Genovese, G; Timmerman, V; Liekens, A; De Rijk, P; Adolfsson, R; Callaerts, P; Del-Favero, J

    2015-04-01

    Sequence analysis of 13 microRNA (miRNA) genes expressed in the human brain and located in genomic regions associated with schizophrenia and/or bipolar disorder, in a northern Swedish patient/control population, resulted in the discovery of two functional variants in the MIR137 gene. On the basis of their location and the allele frequency differences between patients and controls, we explored the hypothesis that the discovered variants impact the expression of the mature miRNA and consequently influence global mRNA expression affecting normal brain functioning. Using neuronal-like SH-SY5Y cells, we demonstrated significantly reduced mature miR-137 levels in the cells expressing the variant miRNA gene. Subsequent transcriptome analysis showed that the reduction in miR-137 expression led to the deregulation of gene sets involved in synaptogenesis and neuronal transmission, all implicated in psychiatric disorders. Our functional findings add to the growing data, which implicate that miR-137 has an important role in the etiology of psychiatric disorders and emphasizes its involvement in nervous system development and proper synaptic function. PMID:24888363

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

    PubMed

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

    2016-02-01

    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

  19. 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

  20. A novel PCCB mutation in a Thai patient with propionic acidemia identified by exome sequencing.

    PubMed

    Porntaveetus, Thantrira; Srichomthong, Chalurmpon; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

    2015-01-01

    Propionic acidemia (PA) is an inborn error of metabolism, caused by mutations in either the PCCA or PCCB gene, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here we report a 6-year-old Thai boy with PA who was born to consanguineous parents. Exome sequencing identified a novel homozygous frameshift insertion (c.379_380insA; p.T127NfsX160) in the PCCB gene, expanding its mutational spectrum. PMID:27081542

  1. A novel PCCB mutation in a Thai patient with propionic acidemia identified by exome sequencing

    PubMed Central

    Porntaveetus, Thantrira; Srichomthong, Chalurmpon; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

    2015-01-01

    Propionic acidemia (PA) is an inborn error of metabolism, caused by mutations in either the PCCA or PCCB gene, leading to mitochondrial accumulation of propionyl-CoA and its by-products. Here we report a 6-year-old Thai boy with PA who was born to consanguineous parents. Exome sequencing identified a novel homozygous frameshift insertion (c.379_380insA; p.T127NfsX160) in the PCCB gene, expanding its mutational spectrum. PMID:27081542

  2. Improving Patient Safety by Identifying Side Effects from Introducing Bar Coding in Medication Administration

    PubMed Central

    Patterson, Emily S.; Cook, Richard I.; Render, Marta L.

    2002-01-01

    Objective. In addition to providing new capabilities, the introduction of technology in complex, sociotechnical systems, such as health care and aviation, can have unanticipated side effects on technical, social, and organizational dimensions. To identify potential accidents in the making, the authors looked for side effects from a natural experiment, the implementation of bar code medication administration (BCMA), a technology designed to reduce adverse drug events (ADEs). Design. Cross-sectional observational study of medication passes before (21 hours of observation of 7 nurses at 1 hospital) and after (60 hours of observation of 26 nurses at 3 hospitals) BCMA implementation. Measurements. Detailed, handwritten field notes of targeted ethnographic observations of in situ nurse–BCMA interactions were iteratively analyzed using process tracing and five conceptual frameworks. Results. Ethnographic observations distilled into 67 nurse–BCMA interactions were classified into 12 categories. We identified five negative side effects after BCMA implementation: (1) nurses confused by automated removal of medications by BCMA, (2) degraded coordination between nurses and physicians, (3) nurses dropping activities to reduce workload during busy periods, (4) increased prioritization of monitored activities during goal conflicts, and (5) decreased ability to deviate from routine sequences. Conclusion. These side effects might create new paths to ADEs. We recommend design revisions, modification of organizational policies, and “best practices” training that could potentially minimize or eliminate these side effects before they contribute to adverse outcomes. PMID:12223506

  3. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

    PubMed

    Dubin, Krista; Callahan, Margaret K; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G; Wolchok, Jedd D

    2016-01-01

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. PMID:26837003

  4. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis

    PubMed Central

    Dubin, Krista; Callahan, Margaret K.; Ren, Boyu; Khanin, Raya; Viale, Agnes; Ling, Lilan; No, Daniel; Gobourne, Asia; Littmann, Eric; Huttenhower, Curtis; Pamer, Eric G.; Wolchok, Jedd D.

    2016-01-01

    The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. PMID:26837003

  5. Urinary Mitochondrial DNA Copy Number Identifies Chronic Renal Injury in Hypertensive Patients.

    PubMed

    Eirin, Alfonso; Saad, Ahmed; Tang, Hui; Herrmann, Sandra M; Woollard, John R; Lerman, Amir; Textor, Stephen C; Lerman, Lilach O

    2016-08-01

    Mitochondrial injury contributes to renal dysfunction in several models of renal disease, but its involvement in human hypertension remains unknown. Fragments of the mitochondrial genome released from dying cells are considered surrogate markers of mitochondrial injury. We hypothesized that hypertension would be associated with increased urine mitochondrial DNA (mtDNA) copy numbers. We prospectively measured systemic and urinary copy number of the mtDNA genes cytochrome-c oxidase-3 and NADH dehydrogenase subunit-1 by quantitative polymerase chain reaction in essential (n=25) and renovascular (RVH, n=34) hypertensive patients and compared them with healthy volunteers (n=22). Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin served as indices of renal injury. Renal blood flow and oxygenation were assessed by multidetector computed tomography and blood oxygen level-dependent magnetic resonance imaging. Blood pressure, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were similarly elevated in essential hypertension and RVH, and estimated glomerular filtration rate was lower in RVH versus healthy volunteers and essential hypertension. Renal blood flow was lower in RVH compared with essential hypertension. Urinary mtDNA copy number was higher in hypertension compared with healthy volunteers, directly correlated with urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 and inversely with estimated glomerular filtration rate. In RVH, urinary mtDNA copy number correlated directly with intrarenal hypoxia. Furthermore, in an additional validation cohort, urinary mtDNA copy number was higher in RVH compared with healthy volunteers (n=10 each). The change in serum creatinine levels and estimated glomerular filtration rate 3 months after medical therapy without or with revascularization correlated with the change in urinary mtDNA. Therefore, elevated urinary mtDNA copy numbers in

  6. The HAS-BLED Score Identifies Patients with Acute Venous Thromboembolism at High Risk of Major Bleeding Complications during the First Six Months of Anticoagulant Treatment

    PubMed Central

    Kooiman, Judith; van Hagen, Nadja; Iglesias del Sol, Antonio; Planken, Erwin V.; Lip, Gregory Y. H.; van der Meer, Felix J. M.; Cannegieter, Suzanne C.; Klok, Frederikus A.; Huisman, Menno V.

    2015-01-01

    Objective The HAS-BLED score enables a risk estimate of major bleeds in patients with atrial fibrillation on vitamin K-antagonists (VKA) treatment, but has not been validated for patients with venous thromboembolism (VTE). We analyzed whether the HAS-BLED score accurately identifies patients at high risk of major bleeds during VKA treatment for acute VTE. Methods Medical records of 537 patients with acute VTE (primary diagnosis pulmonary embolism in 223, deep vein thrombosis in 314) starting VKA treatment between 2006-2007 were searched for items on the HAS-BLED score and the occurrence of major bleeds during the first 180 days of follow-up. The hazard ratio (HR) for the occurrence of major bleeds comparing non-high with high-risk patients as defined by a HAS-BLED score ≥ 3 points was calculated using Cox-regression analysis. Results Major bleeds occurred in 11/537 patients (2.0%, 5.2/100 person years, 95% CI 2.8-9.2). Cumulative incidences of major bleeds were 1.3% (95% CI 0.1-2.5) in the non-high (HAS-BLED < 3) and 9.6% (95%CI 2.2-17.0) in the high-risk group (HAS-BLED ≥ 3), (p <0.0001 by Log-Rank test), with a HR of 8.7 (95% CI 2.7-28.4). Of the items in the HAS-BLED score, abnormal renal function (HR 10.8, 95% CI 1.9-61.7) and a history of bleeding events (HR 10.4, 95% CI 2.5-42.5) were independent predictors of major bleeds during follow-up. Conclusion Acute VTE patients with a HAS-BLED score ≥ 3 points are at increased risk of major bleeding. These results warrant for correction of the potentially reversible risk factors for major bleeding and careful International Normalized Ratio monitoring in acute VTE patients with a high HAS-BLED score. PMID:25905638

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

    PubMed

    Heinzelmann-Schwarz, Viola A; Nixdorf, Sheri; Valadan, Mehrnaz; Diczbalis, Monica; Olivier, Jake; Otton, Geoff; Fedier, André; Hacker, Neville F; Scurry, James P

    2014-04-01

    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

  8. 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

  9. 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

  10. Distinct Disease Phases in Muscles of Facioscapulohumeral Dystrophy Patients Identified by MR Detected Fat Infiltration

    PubMed Central

    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 31P 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

  11. Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

    PubMed

    Nemethova, Martina; Radvanszky, Jan; Kadasi, Ludevit; Ascher, David B; Pires, Douglas E V; Blundell, Tom L; Porfirio, Berardino; Mannoni, Alessandro; Santucci, Annalisa; Milucci, Lia; Sestini, Silvia; Biolcati, Gianfranco; Sorge, Fiammetta; Aurizi, Caterina; Aquaron, Robert; Alsbou, Mohammed; Lourenço, Charles Marques; Ramadevi, Kanakasabapathi; Ranganath, Lakshminarayan R; Gallagher, James A; van Kan, Christa; Hall, Anthony K; Olsson, Birgitta; Sireau, Nicolas; Ayoob, Hana; Timmis, Oliver G; Sang, Kim-Hanh Le Quan; Genovese, Federica; Imrich, Richard; Rovensky, Jozef; Srinivasaraghavan, Rangan; Bharadwaj, Shruthi K; Spiegel, Ronen; Zatkova, Andrea

    2016-01-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy. PMID:25804398

  12. Use of Phylogenetic and Phenotypic Analyses To Identify Nonhemolytic Streptococci Isolated from Bacteremic Patients

    PubMed Central

    Hoshino, Tomonori; Fujiwara, Taku; Kilian, Mogens

    2005-01-01

    The aim of this study was to evaluate molecular and phenotypic methods for the identification of nonhemolytic streptococci. A collection of 148 strains consisting of 115 clinical isolates from cases of infective endocarditis, septicemia, and meningitis and 33 reference strains, including type strains of all relevant Streptococcus species, were examined. Identification was performed by phylogenetic analysis of nucleotide sequences of four housekeeping genes, ddl, gdh, rpoB, and sodA; by PCR analysis of the glucosyltransferase (gtf) gene; and by conventional phenotypic characterization and identification using two commercial kits, Rapid ID 32 STREP and STREPTOGRAM and the associated databases. A phylogenetic tree based on concatenated sequences of the four housekeeping genes allowed unequivocal differentiation of recognized species and was used as the reference. Analysis of single gene sequences revealed deviation clustering in eight strains (5.4%) due to homologous recombination with other species. This was particularly evident in S. sanguinis and in members of the anginosus group of streptococci. The rate of correct identification of the strains by both commercial identification kits was below 50% but varied significantly between species. The most significant problems were observed with S. mitis and S. oralis and 11 Streptococcus species described since 1991. Our data indicate that identification based on multilocus sequence analysis is optimal. As a more practical alternative we recommend identification based on sodA sequences with reference to a comprehensive set of sequences that is available for downloading from our server. An analysis of the species distribution of 107 nonhemolytic streptococci from bacteremic patients showed a predominance of S. oralis and S. anginosus with various underlying infections. PMID:16333101

  13. 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. PMID:27049105

  14. 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

  15. Elevated PEM (Phasic Electromyographic Metric) Rates Identify Rapid Eye Movement Behavior Disorder Patients on Nights Without Behavioral Abnormalities

    PubMed Central

    Bliwise, Donald L.; Rye, David B.

    2008-01-01

    Objective: To determine the validity of the phasic electromyographic metric (PEM) to differentiate patients with a history suggestive of rapid eye movement behavior disorder (REMBD) on laboratory nights without overt dream-enactment behavior. Methods: PEM was quantified as the % of 2.5-sec intervals with phasic muscle activity of 100-msec duration with an amplitude of at least 4 times background activity in 11 patients and 31 elderly controls. Data were derived from both REM and NREM sleep from 5 muscle groups (mentalis, left/right anterior tibialis, left/right brachioradialis). Results: Relative to controls, REMBD patients had significantly higher levels of PEM activity in all recordings. The largest differences occurred during REM sleep for the mentalis and brachioradialis channels. Similar results were obtained by limiting quantification of PEM to the final REM period of the night and could be accomplished by individuals with no previous familiarity with polysomnography. Discussion: PEM may be a useful metric to characterize the REM related phasic muscle activity on patients with a history of REMBD, even when no overt dream-enactment behaviors are detected on a laboratory night. Citation: Bliwise DL; Rye DB. Elevated PEM (phasic electromyographic metric) rates identify rapid eye movement behavior disorder patients on nights without behavioral abnormalities. SLEEP 2008;31(6):853–857. PMID:18548830

  16. Plasma long noncoding RNA expression profile identified by microarray in patients with Crohn’s disease

    PubMed Central

    Chen, Dong; Liu, Jiang; Zhao, Hui-Ying; Chen, Yi-Peng; Xiang, Zun; Jin, Xi

    2016-01-01

    AIM: To investigate the expression pattern of plasma long noncoding RNAs (lncRNAs) in Chrohn’s disease (CD) patients. METHODS: Microarray screening and qRT-PCR verification of lncRNAs and mRNAs were performed in CD and control subjects, followed by hierarchy clustering, GO and KEGG pathway analyses. Significantly dysregulated lncRNAs were categorized into subgroups of antisense lncRNAs, enhancer lncRNAs and lincRNAs. To predict the regulatory effect of lncRNAs on mRNAs, a CNC network analysis was performed and cross linked with significantly changed lncRNAs. The overlapping lncRNAs were randomly selected and verified by qRT-PCR in a larger cohort. RESULTS: Initially, there were 1211 up-regulated and 777 down-regulated lncRNAs as well as 1020 up-regulated and 953 down-regulated mRNAs after microarray analysis; a heat map based on these results showed good categorization into the CD and control groups. GUSBP2 and AF113016 had the highest fold change of the up- and down-regulated lncRNAs, whereas TBC1D17 and CCL3L3 had the highest fold change of the up- and down-regulated mRNAs. Six (SNX1, CYFIP2, CD6, CMTM8, STAT4 and IGFBP7) of 10 mRNAs and 8 (NR_033913, NR_038218, NR_036512, NR_049759, NR_033951, NR_045408, NR_038377 and NR_039976) of 14 lncRNAs showed the same change trends on the microarray and qRT-PCR results with statistical significance. Based on the qRT-PCR verified mRNAs, 1358 potential lncRNAs with 2697 positive correlations and 2287 negative correlations were predicted by the CNC network. CONCLUSION: The plasma lncRNAs profiles provide preliminary data for the non-invasive diagnosis of CD and a resource for further specific lncRNA-mRNA pathway exploration. PMID:27217703

  17. Whole-exome sequencing to identify genetic risk variants underlying inhibitor development in severe hemophilia A patients.

    PubMed

    Gorski, Marcin M; Blighe, Kevin; Lotta, Luca A; Pappalardo, Emanuela; Garagiola, Isabella; Mancini, Ilaria; Mancuso, Maria Elisa; Fasulo, Maria Rosaria; Santagostino, Elena; Peyvandi, Flora

    2016-06-01

    The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly complication of FVIII replacement therapy that affects up to 30% of previously untreated patients with severe hemophilia A. The development of inhibitors is a multifactorial complication involving environmental and genetic factors. Among the latter, F8 gene mutations, ethnicity, family history of inhibitors, and polymorphisms affecting genes involved in the immune response have been previously investigated. To identify novel genetic elements underling the risk of inhibitor development in patients with severe hemophilia A, we applied whole-exome sequencing (WES) and data analysis in a selected group of 26 Italian patients with (n = 17) and without (n = 9) inhibitors. WES revealed several rare, damaging variants in immunoregulatory genes as novel candidate mutations. A case-control association analysis using Cochran-Armitage and Fisher's exact statistical tests identified 1364 statistically significant variants. Hierarchical clustering of these genetic variants showed 2 distinct patterns of homozygous variants with a protective or harmful role in inhibitor development. When looking solely at coding variants, a total of 28 nonsynonymous variants were identified and replicated in 53 inhibitor-positive and 174 inhibitor-negative Italian severe hemophilia A patients using a TaqMan genotyping assay. The genotyping results revealed 10 variants showing estimated odds ratios in the same direction as in the discovery phase and confirmed the association of the rs3754689 missense variant (OR 0.58; 95% CI 0.36-0.94; P = .028) in a highly conserved haplotype region surrounding the LCT locus on chromosome 2q21 with inhibitor development. PMID:27060170

  18. 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.

  19. Exome Sequencing of Cell-Free DNA from Metastatic Cancer Patients Identifies Clinically Actionable Mutations Distinct from Primary Disease.

    PubMed

    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

  20. 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

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

    PubMed

    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

    2016-03-01

    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 = 0.811, and e

  2. 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

  3. Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients.

    PubMed

    Xu, Song; Lou, Feng; Wu, Yi; Sun, Da-Qiang; Zhang, Jing-Bo; Chen, Wei; Ye, Hua; Liu, Jing-Hao; Wei, Sen; Zhao, Ming-Yu; Wu, Wen-Jun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jun

    2016-01-28

    Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future. PMID:26582655

  4. The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs

    PubMed Central

    Charlson, Mary; Wells, Martin T.; Ullman, Ralph; King, Fionnuala; Shmukler, Celia

    2014-01-01

    Background Reducing health care costs requires the ability to identify patients most likely to incur high costs. Our objective was to evaluate the ability of the Charlson comorbidity score to predict the individuals who would incur high costs in the subsequent year and to contrast its predictive ability with other commonly used predictors. Methods We contrasted the prior year Charlson comorbidity index, costs, Diagnostic Cost Group (DCG) and hospitalization as predictors of subsequent year costs from claims data of fund that provides comprehensive health benefits to a large union of health care workers. Total costs in the subsequent year was the principal outcome. Results Of the 181,764 predominantly Black and Latino beneficiaries, 70% were adults (mean age 45.7 years; 62% women). As the comorbidity index increased, total yearly costs increased significantly (P<.001). At lower comorbidity, the costs were similar across different chronic diseases. Using regression to predict total costs, top 5th and 10th percentile of costs, the comorbidity index, prior costs and DCG achieved almost identical explained variance in both adults and children. Conclusions and Relevance The comorbidity index predicted health costs in the subsequent year, performing as well as prior cost and DCG in identifying those in the top 5% or 10%. The comorbidity index can be used prospectively to identify patients who are likely to incur high costs. Trial Registration ClinicalTrials.gov NCT01761253 PMID:25469987

  5. 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

  6. Analysis of undiagnosed tuberculosis-related deaths identified at post-mortem among HIV-infected patients in Russia: a descriptive study

    PubMed Central

    2011-01-01

    Background Tuberculosis remains a serious public health threat and economic burden in Russia with escalating rates of drug resistance against a background of growing HIV-epidemic. Samara Oblast is one of the regions of the Russian Federation where more than 1% of the population is affected by the HIV-epidemic; almost half of the cases are concentrated in the largely-industrial city of Togliatti with a population of 800 000. Methods We conducted a retrospective analysis of errors leading to death of HIV-positive patients in general health care hospitals in Togliatti, Russia, in 2008. All (n = 29) cases when tuberculosis was established at autopsy as a cause of death were included. Results Median length of hospital stay was 20 days; in 11 cases the death occurred within the first 24 hours of admission. All cases were known to be HIV-positive prior to admission, however HAART was not initiated for any case, and no relevant tests to assess severity of immunosupression were performed despite their availability. No appropriate diagnostic algorithms were applied to confirm tuberculosis. Major gaps were identified in the work of hospital and consulting physicians including insufficient records keeping. In almost all patients earlier regular HIV-relevant tests were not performed due to poor compliance of patients, many of whom abused alcohol and drugs. Conclusions We conclude that introduction of prompt and accurate diagnostics tests, adequate treatment protocols and intensive training of physicians in management of AIDS and TB is vital. This should include reviewing standards of care for HIV-positive individuals with accompanying social problems. PMID:22008481

  7. Subspecificities of anticentromeric protein A antibodies identify systemic sclerosis patients at higher risk of pulmonary vascular disease.

    PubMed

    Perosa, Federico; Favoino, Elvira; Favia, Isabella Eleonora; Vettori, Serena; Prete, Marcella; Corrado, Addolorata; Cantatore, Francesco Paolo; Valentini, Gabriele

    2016-06-01

    Patients with systemic sclerosis (SSc) who express autoantibodies to centromeric proteins (CENPs) are at risk of developing pulmonary vascular disease and pulmonary arterial hypertension without fibrosis. Currently no biomarkers are available to predict these complications. We previously characterized the fine specificity of anti-CENP-A antibodies in SSc by screening a phage display library (expressing random 12-mer peptides), and identified phage clones whose peptides were differentially recognized by patients' autoantibodies. Here, we examined if subgroups of SSc patients with different anti-CENP-A antibody subspecificities also differ clinically, and if serum reactivity to phage-displayed peptides can predict pulmonary vascular disease.Clinical data and serum samples were collected from 84 anti-CENP-A-positive SSc patients. Indirect ELISAs were used to test serum reactivity. Pulmonary vascular disease was defined as high systolic pulmonary arterial pressure (sPAP) and low diffusing lung capacity for carbon monoxide (DLCO; percent of predicted values).Sera were screened for reactivity to peptides expressed by phage clones pc4.2 and pc14.1, confirming our earlier observation of differential specificities. Linear regression showed that the levels of antibodies specific for the 2 phage clones were associated with clinical features of pulmonary vascular disease, but in opposite ways: anti-pc4.2 antibodies were positively associated with sPAP and inversely associated with DLCO, whereas anti-pc14.1 antibodies were inversely associated with sPAP and positively associated with DLCO. Anti-pc4.2 and anti-pc14.1 antibody levels predicted sPAP independently of DLCO. These associations were confirmed by logistic regression using antibodies as predictors and dichotomized sPAP (cutoff, 45 mm Hg) as outcome. The ratio of the 2 antibody levels was a useful marker in predicting high sPAP.This study demonstrates that some SSc clinical features associate with subspecificities of

  8. 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

  9. 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

  10. Identifying the Zheng in psoriatic patients based on latent class analysis of traditional Chinese medicine symptoms and signs

    PubMed Central

    2014-01-01

    Background There are approximately five Zhengs reported in psoriatic patients. Systematic data collection and proper analysis for the classification of psoriasis have been lacking. This study aims to cluster the Zhengs in psoriatic patients based on the application of a checklist of traditional Chinese medicine (TCM) symptoms and signs followed by latent class analysis (LCA). Methods A cross-sectional study of 507 psoriatic patients aged above 10 years was performed in Yunnan Provincial Hospital of TCM and the First Affiliated Hospital of Kunming Medicine University from October 2010 to September 2011 using a TCM symptoms and signs checklist obtained from 16 TCM experts by the Delphi technique. LCA was applied to obtain the best fitted model for clustering of symptoms and signs that can be interpreted as underlying Zhengs of psoriasis. Results The LCA identified three Zhengs: dampness-heat Zheng (35.1%); blood heat Zheng (34.7%); and yin deficiency and blood dryness Zheng (30.2%). The first Zheng was associated with winter, the second with male sex, old age, smoking, and drinking alcohol, and the third with outpatient status, which reflected a mild disease course. Conclusions In this study, 507 psoriasis patients were clustered into three Zhengs, which had different associated factors. PMID:24387737

  11. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria

    PubMed Central

    Shen, Hongzhang; Ye, Fuqiang; Xie, Lu; Yang, Jianfeng; Li, Zhen; Xu, Peisong; Meng, Fei; Li, Lei; Chen, Ying; Bo, Xiaochen; Ni, Ming; Zhang, Xiaofeng

    2015-01-01

    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. PMID:26625708

  12. Catalytically impaired hMYH and NEIL1 mutant proteins identified in patients with primary sclerosing cholangitis and cholangiocarcinoma

    PubMed Central

    Forsbring, Monika; Vik, Erik S.; Dalhus, Bjørn; Karlsen, Tom H.; Bergquist, Annika; Schrumpf, Erik; Bjørås, Magnar; Boberg, Kirsten M.; Alseth, Ingrun

    2009-01-01

    The human hMYH and NEIL1 genes encode DNA glycosylases involved in repair of oxidative base damage and mutations in these genes are associated with certain cancers. Primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease characterized by inflammatory destruction of the biliary tree, is often complicated by the development of cholangiocarcinoma (CCA). Here, we aimed to investigate the influence of genetic variations in the hMYH and NEIL1 genes on risk of CCA in PSC patients. The hMYH and NEIL1 gene loci in addition to the DNA repair genes hOGG1, NTHL1 and NUDT1 were analyzed in 66 PSC patients (37 with CCA and 29 without cancer) by complete genomic sequencing of exons and adjacent intronic regions. Several single-nucleotide polymorphisms and mutations were identified and severe impairment of protein function was observed for three non-synonymous variants. The NEIL1 G83D mutant was dysfunctional for the major oxidation products 7,8-dihydro-8-oxoguanine (8oxoG), thymine glycol and dihydrothymine in duplex DNA, and the ability to perform δ-elimination at abasic sites was significantly reduced. The hMYH R260Q mutant had severe defect in adenine DNA glycosylase activity, whereas hMYH H434D could excise adenines from A:8oxoG pairs but not from A:G mispairs. We found no overall associations between the 18 identified variants and susceptibility to CCA in PSC patients; however, the impaired variants may be of significance for carcinogenesis in general. Our findings demonstrate the importance of complete resequencing of selected candidate genes in order to identify rare genetic variants and their possible contribution to individual susceptibility to cancer development. PMID:19443904

  13. Histopathology of duodenal mucosal lesions in pediatric patients with inflammatory bowel disease: statistical analysis to identify distinctive features.

    PubMed

    Hardee, Steven; Alper, Arik; Pashankar, Dinesh S; Morotti, Raffaella A

    2014-01-01

    Histopathologic lesions of the upper gastrointestinal tract (UGT) are common in inflammatory bowel disease (IBD) patients. Pediatric patients have a higher incidence of IBD-associated gastritis and duodenitis than do adults. This study aimed to identify histopathologic features of duodenal lesions in the pediatric population that are characteristic of IBD, compared to duodenal pathology of different etiopathogenesis. We performed a retrospective analysis of UGT biopsies from pediatric patients with a histopathologic diagnosis of duodenitis (0-18 years of age) over a 7-year period. We identified 40 cases of duodenitis associated with Crohn's disease (CD) and 10 cases associated with ulcerative colitis (UC) and compared the histopathologic characteristics of the duodenitis with age-matched controls consisting of 40 cases duodenitis associated with celiac disease and 40 non-Helicobacter pylori-associated (NOS) etiology duodenitis cases. The histologic features that were evaluated included presence of granulomas, duodenal cryptitis, erosion, lamina propria eosinophils, villous blunting, increased intraepithelial lymphocytes (IELs), and crypt hyperplasia, among others. Additionally, we evaluated the presence of associated gastritis in all of these groups. Statistical analysis to identify significant differences was performed using Kruskal-Wallis testing. Cryptitis was the most distinctive feature of IBD-associated duodenitis. Granulomas were exceptionally rare. The severity of villous blunting and presence of IELs was significantly different in the IBD versus the celiac group. There is a significant overlap with duodenal lesions of different etiopathogenesis, including villous blunting and eosinophilia. With the exclusion of granulomas, cryptitis seems the most distinctive feature of the duodenal lesions associated with IBD. PMID:25207874

  14. 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

  15. 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

  16. A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin

    PubMed Central

    Carlton, Edward W; Cullen, Louise; Than, Martin; Gamble, James; Khattab, Ahmed; Greaves, Kim

    2015-01-01

    Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. Results 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. Conclusions The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies. Trial registration number ISRCTN No. 21109279. PMID:25691511

  17. Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum.

    PubMed

    Jouan, Loubna; Ouled Amar Bencheikh, Bouchra; Daoud, Hussein; Dionne-Laporte, Alexandre; Dobrzeniecka, Sylvia; Spiegelman, Dan; Rochefort, Daniel; Hince, Pascale; Szuto, Anna; Lassonde, Maryse; Barbelanne, Marine; Tsang, William Y; Dion, Patrick A; Théoret, Hugo; Rouleau, Guy A

    2016-04-01

    Agenesis of the corpus callosum (ACC) is a common brain malformation which can be observed either as an isolated condition or as part of numerous congenital syndromes. Therefore, cognitive and neurological involvements in patients with ACC are variable, from mild linguistic and behavioral impairments to more severe neurological deficits. To date, the underlying genetic causes of isolated ACC remains elusive and causative genes have yet to be identified. We performed exome sequencing on three acallosal siblings from the same non-consanguineous family and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously reported to cause autosomal recessive primary microcephaly. Our findings suggest a novel role for this gene in the pathogenesis of isolated ACC. PMID:26197979

  18. Subspecificities of anticentromeric protein A antibodies identify systemic sclerosis patients at higher risk of pulmonary vascular disease

    PubMed Central

    Perosa, Federico; Favoino, Elvira; Favia, Isabella Eleonora; Vettori, Serena; Prete, Marcella; Corrado, Addolorata; Cantatore, Francesco Paolo; Valentini, Gabriele

    2016-01-01

    Abstract Patients with systemic sclerosis (SSc) who express autoantibodies to centromeric proteins (CENPs) are at risk of developing pulmonary vascular disease and pulmonary arterial hypertension without fibrosis. Currently no biomarkers are available to predict these complications. We previously characterized the fine specificity of anti-CENP-A antibodies in SSc by screening a phage display library (expressing random 12-mer peptides), and identified phage clones whose peptides were differentially recognized by patients’ autoantibodies. Here, we examined if subgroups of SSc patients with different anti-CENP-A antibody subspecificities also differ clinically, and if serum reactivity to phage-displayed peptides can predict pulmonary vascular disease. Clinical data and serum samples were collected from 84 anti-CENP-A-positive SSc patients. Indirect ELISAs were used to test serum reactivity. Pulmonary vascular disease was defined as high systolic pulmonary arterial pressure (sPAP) and low diffusing lung capacity for carbon monoxide (DLCO; percent of predicted values). Sera were screened for reactivity to peptides expressed by phage clones pc4.2 and pc14.1, confirming our earlier observation of differential specificities. Linear regression showed that the levels of antibodies specific for the 2 phage clones were associated with clinical features of pulmonary vascular disease, but in opposite ways: anti-pc4.2 antibodies were positively associated with sPAP and inversely associated with DLCO, whereas anti-pc14.1 antibodies were inversely associated with sPAP and positively associated with DLCO. Anti-pc4.2 and anti-pc14.1 antibody levels predicted sPAP independently of DLCO. These associations were confirmed by logistic regression using antibodies as predictors and dichotomized sPAP (cutoff, 45 mm Hg) as outcome. The ratio of the 2 antibody levels was a useful marker in predicting high sPAP. This study demonstrates that some SSc clinical features associate with

  19. 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

  20. Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: A 7-Year Comprehensive Analysis of the Known Disease Genes Identify Novel and Recurrent Mutations and Provides an Accurate Assessment of Their Relative Contribution

    PubMed Central

    Jackson, Gail C; Mittaz-Crettol, Laureane; Taylor, Jacqueline A; Mortier, Geert R; Spranger, Juergen; Zabel, Bernhard; Le Merrer, Martine; Cormier-Daire, Valerie; Hall, Christine M; Offiah, Amaka; Wright, Michael J; Savarirayan, Ravi; Nishimura, Gen; Ramsden, Simon C; Elles, Rob; Bonafe, Luisa; Superti-Furga, Andrea; Unger, Sheila; Zankl, Andreas; Briggs, Michael D

    2012-01-01

    Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are relatively common skeletal dysplasias resulting in short-limbed dwarfism, joint pain, and stiffness. PSACH and the largest proportion of autosomal dominant MED (AD-MED) results from mutations in cartilage oligomeric matrix protein (COMP); however, AD-MED is genetically heterogenous and can also result from mutations in matrilin-3 (MATN3) and type IX collagen (COL9A1, COL9A2, and COL9A3). In contrast, autosomal recessive MED (rMED) appears to result exclusively from mutations in sulphate transporter solute carrier family 26 (SLC26A2). The diagnosis of PSACH and MED can be difficult for the nonexpert due to various complications and similarities with other related diseases and often mutation analysis is requested to either confirm or exclude the diagnosis. Since 2003, the European Skeletal Dysplasia Network (ESDN) has used an on-line review system to efficiently diagnose cases referred to the network prior to mutation analysis. In this study, we present the molecular findings in 130 patients referred to ESDN, which includes the identification of novel and recurrent mutations in over 100 patients. Furthermore, this study provides the first indication of the relative contribution of each gene and confirms that they account for the majority of PSACH and MED. Hum Mutat 33:144–157, 2012. © 2011 Wiley Periodicals, Inc. PMID:21922596

  1. Newborn screening for severe T and B cell lymphopenia identifies a fraction of patients with Wiskott-Aldrich syndrome.

    PubMed

    Borte, Stephan; Fasth, Anders; von Döbeln, Ulrika; Winiarski, Jacek; Hammarström, Lennart

    2014-11-01

    The lack or marked reduction of recently formed T and B cells provides a basis for neonatal screening for severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). Newborns with other conditions are also identified if a severe T or B cell lymphopenia is present at birth. We retrospectively analyzed Guthrie card samples from 11 children with Wiskott-Aldrich syndrome (WAS), a rare disease that requires early diagnosis and treatment, to determine whether combined T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) screening could identify these patients. 4 of 11 patients showed markedly reduced TREC or KREC copy numbers in their DBS as compared to storage-time matched controls and prospectively screened Swedish and German newborns. No correlation was observed between the WAS gene mutations, the clinical severity/course and the result of the screening assay. A diagnosis of WAS should thus be considered in newborns with positive TREC or KREC screening results. PMID:25217881

  2. Identifying Gene Disruptions in Novel Balanced de novo Constitutional Translocations in Childhood Cancer Patients by Whole Genome Sequencing

    PubMed Central

    Ritter, Deborah I.; Haines, Katherine; Cheung, Hannah; Davis, Caleb F.; Lau, Ching C.; Berg, Jonathan S.; Brown, Chester W.; Thompson, Patrick A.; Gibbs, Richard; Wheeler, David A.; Plon, Sharon E.

    2014-01-01

    Purpose We applied whole genome sequencing to children diagnosed with neoplasms and found to carry apparently balanced constitutional translocations, to discover novel genic disruptions. Methods We applied SV calling programs CREST, Break Dancer, SV-STAT and CGAP-CNV, and developed an annotative filtering strategy to achieve nucleotide resolution at the translocations. Results We identified the breakpoints for t(6;12) (p21.1;q24.31) disrupting HNF1A in a patient diagnosed with hepatic adenomas and Maturity Onset Diabetes of the Young (MODY). Translocation as the disruptive event of HNF1A, a gene known to be involved in MODY3, has not been previously reported. In a subject with Hodgkin’s lymphoma and subsequent low-grade glioma, we identified t(5;18) (q35.1;q21.2), disrupting both SLIT3 and DCC, genes previously implicated in both glioma and lymphoma. Conclusions These examples suggest that implementing clinical whole genome sequencing in the diagnostic work-up of patients with novel but apparently balanced translocations may reveal unanticipated disruption of disease-associated genes and aid in prediction of the clinical phenotype. PMID:25569436

  3. 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

  4. 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

  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. PMID:24233152

  6. In-111 polyclonal HIG identifies patients but not atherosclerotic lesions at risk - a 5 years follow-up.

    PubMed

    Berent, Robert; Auer, Johann; Granegger, Susanne; Sinzinger, Helmut

    2015-01-01

    There is a strong need for non-invasive detection of human atherosclerotic lesions. One of the radioisotopic approaches using Indium-111-HIG has been shown to accumulate in oxidized LDL-rich foam cells and inflammatory vascular lesions. Earlier human studies in 200 patients, 100 with peripheral vascular disease and 100 with carotid artery disease comparing In-111-HIG scintigraphy with sonographic data revealed a high sensitivity (70%-77%) but a very low specificity (33%-41%). At this time we concluded the approach "not promising" for human studies. However, clinical follow-up over 5 years now shows that those patients with positive In-111-HIG scintigraphy exhibited a significantly higher vascular morbidity (P<0,01) and mortality (P<0,01), especially in the immediate follow-up period. Retrospective analysis discovered higher CRP and isoprostane (8-epi-prostaglandin (PG) F2α) levels in HIG-positive patients at the time of scintigraphy. These findings indicate that In-111-HIG reflecting vascular lesions with a high inflammatory component, probably more prone to rupture, may identify a population at high vascular risk rather than a lesion at risk. The clinical impact of this finding should be assessed in prospective studies. PMID:26665225

  7. 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. PMID:22177941

  8. 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. PMID:26402792

  9. 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

  10. Mandatory oral glucose tolerance tests identify more diabetics in stable patients with chronic heart failure: a prospective observational study

    PubMed Central

    2014-01-01

    Background Many patients with chronic heart failure (CHF) are believed to have unrecognized diabetes, which is associated with a worse prognosis. This study aimed to describe glucose tolerance in a general stable CHF population and to identify determinants of glucose tolerance focusing on body composition and skeletal muscle strength. Methods A prospective observational study was set up. Inclusion criteria were diagnosis of CHF, stable condition and absence of glucose-lowering medication. Patients underwent a 2 h oral glucose tolerance test (OGTT), isometric strength testing of the upper leg and dual energy x-ray absorptiometry. Health-related quality of life and physical activity level were assessed by questionnaire. Results Data of 56 participants were analyzed. Despite near-normal fasting glucose values, 55% was classified as prediabetic, 14% as diabetic, and 20% as normal glucose tolerant. Of all newly diagnosed diabetic patients, 79% were diagnosed because of 2 h glucose values only and none because of HbA1c. Univariate mixed model analysis revealed ischaemic aetiology, daily physical activity, E/E’, fat trunk/fat limbs and extension strength as possible explanatory variables for the glucose curve during the glucose tolerance test. When combined in one model, only fat trunk/fat limbs and E/E’ remained significant predictors. Furthermore, fasting insulin was correlated with fat mass/height2 (r = 0.51, p < 0.0001), extension strength (r = -0.33, p < 0.01) and triglycerides (r = 0.39, p < 0.01). Conclusions Our data confirm that a large majority of CHF patients have impaired glucose tolerance. This glucose intolerance is related to fat distribution and left ventricular end-diastolic pressure. PMID:24673860

  11. Simulation of Daily Snapshot Rhythm Monitoring to Identify Atrial Fibrillation in Continuously Monitored Patients with Stroke Risk Factors

    PubMed Central

    Yano, Yuichiro; Greenland, Philip; Lloyd-Jones, Donald M.; Daoud, Emile G.; Koehler, Jodi L.; Ziegler, Paul D.

    2016-01-01

    Background New technologies are diffusing into medical practice swiftly. Hand-held devices such as smartphones can record short-duration (e.g., 1-minute) ECGs, but their effectiveness in identifying patients with paroxysmal atrial fibrillation (AF) is unknown. Methods We used data from the TRENDS study, which included 370 patients (mean age 71 years, 71% men, CHADS2 score≥1 point: mean 2.3 points) who had no documentation of atrial tachycardia (AT)/AF or antiarrhythmic or anticoagulant drug use at baseline. All were subsequently newly diagnosed with AT/AF by a cardiac implantable electronic device (CIED) over one year of follow-up. Using a computer simulation approach (5,000 repetitions), we estimated the detection rate for paroxysmal AT/AF via daily snapshot ECG monitoring over various periods, with the probability of detection equal to the percent AT/AF burden on each day. Results The estimated AT/AF detection rates with snapshot monitoring periods of 14, 28, 56, 112, and 365 days were 10%, 15%, 21%, 28%, and 50% respectively. The detection rate over 365 days of monitoring was higher in those with CHADS2 scores ≥2 than in those with CHADS2 scores of 1 (53% vs. 38%), and was higher in those with AT/AF burden ≥0.044 hours/day compared to those with AT/AF burden <0.044 hours/day (91% vs. 14%; both P<0.05). Conclusions Daily snapshot ECG monitoring over 365 days detects half of patients who developed AT/AF as detected by CIED, and shorter intervals of monitoring detected fewer AT/AF patients. The detection rate was associated with individual CHADS2 score and AT/AF burden. Trial Registration ClinicalTrials.gov NCT00279981 PMID:26882334

  12. 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. PMID:26216230

  13. 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

  14. Grading More Accurately

    ERIC Educational Resources Information Center

    Rom, Mark Carl

    2011-01-01

    Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

  15. Automated analysis of vital signs to identify patients with substantial bleeding before hospital arrival: a feasibility study.

    PubMed

    Liu, Jianbo; Khitrov, Maxim Y; Gates, Jonathan D; Odom, Stephen R; Havens, Joaquim M; de Moya, Marc A; Wilkins, Kevin; Wedel, Suzanne K; Kittell, Erin O; Reifman, Jaques; Reisner, Andrew T

    2015-05-01

    Trauma outcomes are improved by protocols for substantial bleeding, typically activated after physician evaluation at a hospital. Previous analysis suggested that prehospital vital signs contained patterns indicating the presence or absence of substantial bleeding. In an observational study of adults (aged ≥18 years) transported to level I trauma centers by helicopter, we investigated the diagnostic performance of the Automated Processing of the Physiological Registry for Assessment of Injury Severity (APPRAISE) system, a computational platform for real-time analysis of vital signs, for identification of substantial bleeding in trauma patients with explicitly hemorrhagic injuries. We studied 209 subjects prospectively and 646 retrospectively. In our multivariate analysis, prospective performance was not significantly different from retrospective. The APPRAISE system was 76% sensitive for 24-h packed red blood cells of 9 or more units (95% confidence interval, 59% - 89%) and significantly more sensitive (P < 0.05) than any prehospital Shock Index of 1.4 or higher; sensitivity, 59%; initial systolic blood pressure (SBP) less than 110 mmHg, 50%; and any prehospital SBP less than 90 mmHg, 50%. The APPRAISE specificity for 24-h packed red blood cells of 0 units was 87% (88% for any Shock Index ≥1.4, 88% for initial SBP <110 mmHg, and 90% for any prehospital SBP <90 mmHg). Median APPRAISE hemorrhage notification time was 20 min before arrival at the trauma center. In conclusion, APPRAISE identified bleeding before trauma center arrival. En route, this capability could allow medics to focus on direct patient care rather than the monitor and, via advance radio notification, could expedite hospital interventions for patients with substantial blood loss. PMID:25664983

  16. Altered Secretory Activity of APE1/Ref-1 D148E Variants Identified in Human Patients With Bladder Cancer

    PubMed Central

    2016-01-01

    Purpose: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA repair and redox modulation. Recently, serum and urinary APE1/Ref-1 levels were reported to be increased in patients with bladder cancer. Genetic variations of APE/Ref-1 are associated with the risk of cancer. However, the effect of APE1/Ref-1 variants on its secretory activity is yet unknown. Methods: APE1/Ref-1 variants were evaluated by DNA sequencing analysis of reverse transcription polymerase chain reaction products in coding DNA sequences (CDS) of APE1/Ref-1 in bladder tissue samples from patients with bladder cancer (n=10). Secretory activity of APE1/Ref-1 variants was evaluated with immunoblot and enzyme-linked immunosorbent assay of the culture medium supernatants. Results: Four different substitution mutants (D148E, I64V/D148E, W67R/D148E, and E86G/D148E) of APE1/Ref-1 were identified in bladder cancer specimens. However, deletion mutants of APE1/Ref-1 CDS were not found. The secretory activity of the APE1/Ref-1 variants (D148E, I64V/D148E, and E86G/D148E) was increased compared to that of wild type APE1/Ref-1. Furthermore, the secretory activity in basal or hyperacetylated conditions was much higher than that in APE1/Ref-1 D148E-transfected HEK293 cells. Conclusions: Taken together, our data suggest that the increased secretory activity of D148E might contribute to increased serum levels of APE1/Ref-1 in patients with bladder cancer. PMID:27230458

  17. DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations

    PubMed Central

    Marzese, Diego M.; Scolyer, Richard A.; Roqué, Maria; Vargas-Roig, Laura M.; Huynh, Jamie L.; Wilmott, James S.; Murali, Rajmohan; Buckland, Michael E.; Barkhoudarian, Garni; Thompson, John F.; Morton, Donald L.; Kelly, Daniel F.; Hoon, Dave S. B.

    2014-01-01

    Background The brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets. Methods Genome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing. Results MBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Deletions were frequently detected in the CDKN2A/B locus. Of MBMs, 46.1% and 28.8% had BRAF and NRAS missense mutations, respectively. Compared with lung and liver metastases, MBMs exhibited higher frequency of CDH13 hypermethylation and CDKN2A/B locus deletion. Mutual exclusivity between hypermethylated genes and CDKN2A/B locus deletion identified 2 clinically relevant molecular subtypes of MBMs. CDKN2A/B deletions were associated with multiple MBMs and frequently hypermethylated genes with shorter time to brain metastasis. Conclusions Melanoma cells that colonize the brain harbor numerous genetically and epigenetically altered genes. This study presents an integrated genomic and epigenomic analysis that reveals MBM-specific molecular alterations and mutually exclusive molecular subtypes. PMID:24968695

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study

    PubMed Central

    Lee, Susan Shin-Jung; Lin, Hsi-Hsun; Tsai, Hung-Chin; Su, Ih-Jen; Yang, Chin-Hui; Sun, Hsin-Yun; Hung, Chien-Chin; Sy, Cheng-Len; Wu, Kuan-Sheng; Chen, Jui-Kuang; Chen, Yao-Shen; Fang, Chi-Tai

    2015-01-01

    Background Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. Materials and Methods A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. Results Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49–15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52–24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587–0.798) for the study cohort and 0.792 (95% CI: 0.776–0.808) and 0.766 in the 2 validation cohorts. Conclusions A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The

  4. Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

    PubMed Central

    Leidy, Nancy K; Kim, Katherine; Bacci, Elizabeth D; Yawn, Barbara P; Mannino, David M; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K; Meldrum, Catherine A; Make, Barry J; Bowler, Russ P; Steenrod, Anna W; Murray, Lindsey T; Walsh, John W; Martinez, Fernando

    2015-01-01

    Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. Results: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. Conclusions: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. PMID:26028486

  5. Is there a Role for Gallium-67 Citrate SPECT/CT, in Patients with Renal Impairment or Who are Renal Transplant Recipients, in Identifying and Localizing Suspected Infection?

    PubMed Central

    Nowosinska, Ewa; Navalkissoor, Shaunak; Quigley, Ann Marie; Buscombe, John R.

    2015-01-01

    To assess the added value of single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with end-stage renal failure (ESRF) or renal transplant recipients in whom focal infection was suspected. Gallium-67 (Ga-67) citrate scintigrams of 18 patients (10 in ESRF and eight with renal transplants) were reviewed. Sites of abnormal uptake seen on the whole body and SPECT were noted. A SPECT/CT was also reviewed to see if additional information could be obtained. Imaging results were compared with the final diagnosis. Overall, 14 out of 18 (78%) patients had a proven cause to explain symptoms while four patients did not have a final cause identified. Infection was proven in the final diagnosis in 12 out of 14 (86%) patients. Of the 10 patients with ESRF, six had confirmed infection with the Ga-67 citrate study correctly identifying five out of six (83%) patients, and SPECT/CT providing additional information in four out of five (80%) patients. In the eight renal transplant recipients, six had a confirmed source of infection (all identified by the Ga-67 citrate study). SPECT/CT provided additional information in two out of six (33%) patients. Ga-67 citrate imaging had an overall sensitivity of 13/14 (93%), with one false negative. SPECT/CT provided an additional contribution in eight out of 18 (44%) patients by better defining the location/extent of infection and differentiating the physiological from the pathological uptake. PMID:26420989

  6. 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.

  7. NOTE: How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

    NASA Astrophysics Data System (ADS)

    Roberts, Ralph

    2001-09-01

    The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However, the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth, 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.

  8. 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

  9. 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.

  10. Accurate measurement of time

    NASA Astrophysics Data System (ADS)

    Itano, Wayne M.; Ramsey, Norman F.

    1993-07-01

    The paper discusses current methods for accurate measurements of time by conventional atomic clocks, with particular attention given to the principles of operation of atomic-beam frequency standards, atomic hydrogen masers, and atomic fountain and to the potential use of strings of trapped mercury ions as a time device more stable than conventional atomic clocks. The areas of application of the ultraprecise and ultrastable time-measuring devices that tax the capacity of modern atomic clocks include radio astronomy and tests of relativity. The paper also discusses practical applications of ultraprecise clocks, such as navigation of space vehicles and pinpointing the exact position of ships and other objects on earth using the GPS.

  11. 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.

  12. 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

  13. 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. PMID:26980748

  14. Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation

    PubMed Central

    Won, Brian M.; Patton, Kathryn Alexa; Villaflor, Victoria M.; Hoffman, Philip C.; Hensing, Thomas; Hogarth, D. Kyle; Malik, Renuka; MacMahon, Heber; Mueller, Jeffrey; Simon, Cassie A.; Vigneswaran, Wickii T.; Wigfield, Christopher H.; Ferguson, Mark K.; Husain, Aliya N.; Vokes, Everett E.; Salgia, Ravi

    2016-01-01

    This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular Intelligence, and Response Genetics Inc. For the entire adenocarcinoma cohort, 25% of patients were African Americans; 90% of KRAS mutations were detected in smokers, including current and former smokers; 46% of EGFR and 61% of ALK alterations were detected in never smokers. 99.4% of patients, whose samples were analyzed by next-generation sequencing (NGS), had genetic alterations identified with an average of 10.8 alterations/tumor throughout different tumor subtypes. However, mutations were not mutually exclusive. NGS in this study identified potentially targetable genetic alterations in the majority of patients tested, detected concurrent alterations and provided information on variants of unknown significance at this time but potentially targetable in the future. PMID:26934441

  15. Understanding the Code: keeping accurate records.

    PubMed

    Griffith, Richard

    2015-10-01

    In his continuing series looking at the legal and professional implications of the Nursing and Midwifery Council's revised Code of Conduct, Richard Griffith discusses the elements of accurate record keeping under Standard 10 of the Code. This article considers the importance of accurate record keeping for the safety of patients and protection of district nurses. The legal implications of records are explained along with how district nurses should write records to ensure these legal requirements are met. PMID:26418404

  16. Usefulness of cardiac meta-iodobenzylguanidine imaging to identify patients with chronic heart failure and left ventricular ejection fraction <35% at low risk for sudden cardiac death.

    PubMed

    Kawai, Tsutomu; Yamada, Takahisa; Tamaki, Shunsuke; Morita, Takashi; Furukawa, Yoshio; Iwasaki, Yusuke; Kawasaki, Masato; Kikuchi, Atsushi; Kondo, Takumi; Takahashi, Satoshi; Ishimi, Masashi; Hakui, Hideyuki; Ozaki, Tatsuhisa; Sato, Yoshihiro; Seo, Masahiro; Sakata, Yasushi; Fukunami, Masatake

    2015-06-01

    Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD) are often treated with implantable cardiac defibrillators (ICDs). However, current criteria for device use that is based largely on left ventricular ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver therapy. It is of clinical significance to identify patients who do not require ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information about CHF, whether it can identify patients with CHF who do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF <35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0 to 5, according to the degree of deviation from control values. The study patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and high (8 to 10), according to the MIBG scores defined as the sum of the H/M and washout rate scores. Sixteen patients died of SCD during a follow-up period. Patients with low MIBG score had a significantly lower risk of SCD than those with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%; high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score for identifying patients without SCD was 100%. In conclusion, the MIBG score can identify patients with CHF and LVEF <35% who have low risk of developing SCD. PMID:25851796

  17. 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

  18. Pediatric emergency department overcrowding: electronic medical record for identification of frequent, lower acuity visitors. Can we effectively identify patients for enhanced resource utilization?

    PubMed

    Simon, Harold K; Hirsh, Daniel A; Rogers, Alexander J; Massey, Robert; Deguzman, Michael A

    2009-04-01

    The objective of this study was to utilize the electronic medical record system to identify frequent lower acuity patients presenting to the Pediatric Emergency Department and to evaluate their impact on Pediatric Emergency Department overcrowding and resource utilization. The electronic medical records (EMR) of two pediatric emergency centers were reviewed from August 2002 to November 2004. Pediatric Emergency Department encounters that met any of the following criteria were classified as Visits Necessitating Pediatric Emergency Department care (VNEC): Disposition of admission, transfer or deceased; Intravenous fluids (IVF) or medications (excluding single antipyretic or antihistamine); Radiology or laboratory tests (excluding Rapid Strep); Fractures, dislocations, and febrile seizures. All other visits were classified as non-VNEC. ICD-9 (International Classification of Diseases, Ninth Revision) codes from the Pediatric Emergency Department encounters were defined as representing chronic or non-chronic conditions. Patients were then evaluated for utilization patterns, frequency of Emergency Department (ED) visits, chronic illness, and VNEC status. There were 153,390 patients identified, representing 255,496 visits (1.7 visits/patient, range 1-49). Overall, 189,998 visits (74%) required defined ED services and were categorized as VNEC, with the remaining 65,498 visits (26%) categorized as non-VNEC. With increasing visits, a steady decline in those requiring ED services was observed, with a plateau by visit six (VNEC 77% @ one visit, 64% @ six visits, p < 0.001). There were 141,765 patients seen fewer than four times, representing 92% of the patients and 74% of all visits (1.3 visits/patient, 225 visits/day). In contrast, 2664 patients disproportionately utilized the ED more than six times (maximum 49), representing 1.7% of patients and 9.8% of visits (9.4 visit/patient, 30 visits/day, p < 0.001). Excluding patients with chronic illness, 1074 patients also

  19. A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation

    PubMed Central

    2013-01-01

    Background Focal segmental glomerulosclerosis (FSGS) is a frequent cause of end-stage renal disease. Renal transplantation in patients with FSGS is often complicated by disease recurrence, which is associated with poor outcome. There are no tests that reliably predict recurrence of FSGS after transplantation. The aim of this study was to evaluate if clinical criteria can identify patients at high risk for recurrent disease. Methods We retrospectively studied 94 patients who received a first renal transplant at a median age of 37 years (range 5–69 years). Patients were assigned to one of three groups: familial or genetic FSGS (group I; n=18), secondary FSGS (group II; n=10) and idiopathic FSGS (group III; n=66). Pretransplant clinical characteristics were analyzed to determine predictors of a recurrence after transplantation. Results FSGS only recurred in patients with idiopathic FSGS (group III; 42%). Patients with a recurrence had a significantly lower serum albumin, higher 24-hour proteinuria and higher estimated glomerular filtration rate at diagnosis. Serum albumin at diagnosis was the only independent predictor of a recurrence in patients with idiopathic FSGS. Patients with recurrent FSGS had more acute rejection episodes (54% vs. 27%, P =0.02) and lower five year graft survival compared to patients without a recurrence (50 vs. 82%, P <0.01). Conclusions Clinical criteria allow identification of patients at high risk of recurrent FSGS after renal transplantation. This information can be used in the counseling and management of patients with FSGS. PMID:23433074

  20. A computer-based interview to identify HIV risk behaviors and to assess patient preferences for HIV-related health states.

    PubMed Central

    Sanders, G. D.; Owens, D. K.; Padian, N.; Cardinalli, A. B.; Sullivan, A. N.; Nease, R. F.

    1994-01-01

    We developed a computer-based utility assessment tool to assess the preferences of patients towards HIV-related health states and identify risk behaviors (both sexual and drug related) of the patient being interviewed. The reliability of the computer-based interview was assessed through comparison with person-to-person interviews. Our pilot study included 22 patients. Twelve of these patients were also interviewed by the research assistants in person-to-person interviews. The agreement between the person-to-person and computer-based interviews was excellent (3 discrepancies of 180 compared answers), and the majority of the patients preferred to use the computer to disclose sensitive information regarding risk behaviors. Our study suggests that assessment of patient preferences and risk factors can be performed reliably through a computer-based interview. PMID:7949919

  1. Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases

    PubMed Central

    Naessens, James M; Visscher, Sue L; Peterson, Stephanie M; Swanson, Kristi M; Johnson, Matthew G; Rahman, Parvez A; Schindler, Joe; Sonneborn, Mark; Fry, Donald E; Pine, Michael

    2015-01-01

    Objective Assess algorithms for linking patients across de-identified databases without compromising confidentiality. Data Sources/Study Setting Hospital discharges from 11 Mayo Clinic hospitals during January 2008–September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). Study Design Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. Data Collection/Extraction Methods De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). Principal Findings Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. Conclusion Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications. PMID:26073819

  2. Magnetic Resonance Imaging after Completion of Neoadjuvant Chemotherapy Can Accurately Discriminate between No Residual Carcinoma and Residual Ductal Carcinoma In Situ in Patients with Triple-Negative Breast Cancer

    PubMed Central

    Park, Seho; Yoon, Jung Hyun; Sohn, Joohyuk; Park, Hyung Seok; Moon, Hee Jung; Kim, Min Jung; Kim, Eun-Kyung; Kim, Seung Il; Park, Byeong-Woo

    2016-01-01

    Background The accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT) is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0) from residual ductal carcinoma in situ (ypTis) in breast cancer patients who received NCT. Patients and Methods Parameters of 117 patients attaining pathological complete response (CR) in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI) before and after NCT. Results There were 67 (57.3%) patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2)-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR), 4.23; 95% confidence interval (CI), 1.11–16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53–17.85). Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5%) were ypT0 after NCT. Conclusion Among imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2

  3. Sleep Disordered Breathing in Heart Failure: Identifying and Treating an Important but Often Unrecognized Comorbidity in Heart Failure Patients

    PubMed Central

    Khayat, Rami; Small, Roy; Rathman, Lisa; Krueger, Steven; Gocke, Becky; Clark, Linda; Yamokoski, Laura; Abraham, William T.

    2013-01-01

    Sleep disordered breathing (SDB) is the most common co-morbidity in patients with heart failure (HF) and has a significant impact on quality of life, morbidity, and mortality. A number of therapeutic options have become available in recent years that can improve quality of life and potentially the outcomes of HF patients with SDB. Unfortunately, SDB is not part of the routine evaluation and management of HF, thus it remains untreated in most HF patients. While recognition of the role of SDB in HF is increasing, clinical guidelines for the management of SDB in HF patients continue to be absent. In this article we provide an overview of SDB in HF and propose a clinical care pathway to help clinicians better recognize and treat SDB in their HF patients. PMID:23743494

  4. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients

    PubMed Central

    Hu, Donglei; Martino, Alessandro; Serie, Daniel; Curtin, Karen; Campa, Daniele; Aftab, Blake; Bracci, Paige; Buda, Gabriele; Zhao, Yi; Caswell-Jin, Jennifer; Diasio, Robert; Dumontet, Charles; Dudziński, Marek; Fejerman, Laura; Greenberg, Alexandra; Huntsman, Scott; Jamroziak, Krzysztof; Jurczyszyn, Artur; Kumar, Shaji; Atanackovic, Djordje; Glenn, Martha; Cannon-Albright, Lisa A.; Jones, Brandt; Lee, Adam; Marques, Herlander; Martin, Thomas; Martinez-Lopez, Joaquin; Rajkumar, Vincent; Sainz, Juan; Vangsted, Annette Juul; Wątek, Marzena; Wolf, Jeffrey; Slager, Susan; Camp, Nicola J; Canzian, Federico; Vachon, Celine

    2015-01-01

    Here we perform the first genome wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; p=6 × 10−10). Patients with the minor allele are at increased risk for mortality (HR 2.65; 95% CI: 1.94 – 3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 p=0.044). Using publically available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival.. Polymorphisms at the FOPNL locus are associated with survival among MM patients. PMID:26198393

  5. Usefulness of Decrease in Oxygen Uptake Efficiency to Identify Gas Exchange Abnormality in Patients with Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Yang, Wenlan; Guo, Jian; Zhang, Yan; Sapkota, Rikesh; Kushwaha, Shailendra Prasad; Gong, Sugang; Sun, Xingguo; Liu, Jinming

    2014-01-01

    Background Decline in oxygen uptake efficiency (OUE), especially during exercise, is found in patients with chronic heart failure. In this study we aimed to test the validity and usefulness of OUE in evaluating gas exchange abnormality of patients with idiopathic pulmonary arterial hypertension (IPAH). Methods We retrospectively investigated the cardiopulmonary exercise test (CPET) with gas exchange measurements in 32 patients with confirmed IPAH. All patients also had resting hemodynamic measurements and pulmonary function test (PFT). Sixteen healthy subjects, matched by age, sex, and body size were used as controls, also had CPET and PFT measurements. Results In IPAH patients, the magnitude of absolute and percentage of predicted (%pred) oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP), as well as several other CPET parameters, were strikingly worse than healthy subjects (P<0.0001). Pattern of changes in OUE in patients is similar to that in controls, In IPAH patients, OUE values at rest, warming up, anaerobic threshold and peak exercise were all significantly lower than in normal (P<0.0001). OUEP%pred, better than OUES%pred, correlated significantly with New York Heart Association (NYHA) functional Class (r = −0.724, P<0.005), Total Pulmonary Vascular Resistance (TPVR) (r = −0.694, P<0.005), diffusing capacity for carbon monoxide (DLCO) (r = 0.577, P<0.05), and the lowest ventilation versus CO2 output ratio during exercise (LowestV˙E/V˙CO2) (r = −0.902, P<0.0001). In addition, the coefficient of variation (COV) of OUEP was lower (20.9%) markedly than OUES (34.3%) (P<0.0001). Conclusions In patients with IPAH, OUES and OUEP are both significantly lower than the healthy subjects. OUEP is a better physiological parameter than OUES in evaluating the gas exchange abnormality of patients with IPAH. PMID:24905576

  6. 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. PMID:27086989

  7. Clinical Prediction Rule for Patient Outcome after In-Hospital CPR: A New Model, Using Characteristics Present at Hospital Admission, to Identify Patients Unlikely to Benefit from CPR after In-Hospital Cardiac Arrest

    PubMed Central

    Merja, Satyam; Lilien, Ryan H; Ryder, Hilary F

    2015-01-01

    BACKGROUND Physicians and patients frequently overestimate likelihood of survival after in-hospital cardiopulmonary resuscitation. Discussions and decisions around resuscitation after in-hospital cardiopulmonary arrest often take place without adequate or accurate information. METHODS We conducted a retrospective chart review of 470 instances of resuscitation after in-hospital cardiopulmonary arrest. Individuals were randomly assigned to a derivation cohort and a validation cohort. Logistic Regression and Linear Discriminant Analysis were used to perform multivariate analysis of the data. The resultant best performing rule was converted to a weighted integer tool, and thresholds of survival and nonsurvival were determined with an attempt to optimize sensitivity and specificity for survival. RESULTS A 10-feature rule, using thresholds for survival and nonsurvival, was created; the sensitivity of the rule on the validation cohort was 42.7% and specificity was 82.4%. In the Dartmouth Score (DS), the features of age (greater than 70 years of age), history of cancer, previous cardiovascular accident, and presence of coma, hypotension, abnormal PaO2, and abnormal bicarbonate were identified as the best predictors of nonsurvival. Angina, dementia, and chronic respiratory insufficiency were selected as protective features. CONCLUSIONS Utilizing information easily obtainable on admission, our clinical prediction tool, the DS, provides physicians individualized information about their patients’ probability of survival after in-hospital cardiopulmonary arrest. The DS may become a useful addition to medical expertise and clinical judgment in evaluating and communicating an individual’s probability of survival after in-hospital cardiopulmonary arrest after it is validated by other cohorts. PMID:26448686

  8. A novel rare copy number variant of the ABCF1 gene identified among dengue fever patients from Peninsular Malaysia.

    PubMed

    Hoh, B P; Sam, S S; Umi, S H; Mahiran, M; Nik Khairudin, N Y; Rafidah Hanim, S; Abubakar, S

    2014-01-01

    Copy number variation (CNV) is a form of genetic variation in addition to single nucleotide polymorphisms. The significance of CNV in the manifestation of a number of diseases is only recently receiving considerable attention. We genotyped 163 dengue patients from Peninsular Malaysia for genes possibly linked to dengue infection using quantitative real-time PCR. Here, we report a serendipitous discovery of a novel rare CNV of the ABCF1 gene among the dengue patients. Among these patients, two had a gain of 1 copy (CN = 3) and one had lost 1 copy (CN = 1), indicating that a rare CNV of the ABCF1 gene was detected among dengue patients from Peninsular Malaysia. Although the gene is suspected to regulate inflammatory responses and pathogen-induced cytokine storm, its relevance to dengue requires further investigation. PMID:24634119

  9. Preferences of diabetes patients and physicians: A feasibility study to identify the key indicators for appraisal of health care values

    PubMed Central

    2010-01-01

    Background Evidence-based medicine, the Institute of Medicine (IOM) and the German Institute for Quality and Efficiency in Health Care (IQWiG), support the inclusion of patients' preferences in health care decisions. In fact there are not many trials which include an assessment of patient's preferences. The aim of this study is to demonstrate that preferences of physicians and of patients can be assessed and that this information may be helpful for medical decision making. Method One of the established methods for assessment of preferences is the conjoint analysis. Conjoint analysis, in combination with a computer assisted telephone interview (CATI), was used to collect data from 827 diabetes patients and 60 physicians, which describe the preferences expressed as levels of four factors in the management and outcome of the disease. The first factor described the main treatment effect (reduction of elevated HbA1c, improved well-being, absence of side effects, and no limitations of daily life). The second factor described the effect on the body weight (gain, no change, reduction). The third factor analyzed the mode of application (linked to meals or flexible application). The fourth factor addressed the type of product (original brand or generic product). Utility values were scaled and normalized in a way that the sum of utility points across all levels is equal to the number of attributes (factors) times 100. Results The preference weights confirm that the reduction of body weight is at least as important for patients - especially obese patients - and physicians as the reduction of an elevated HbA1c. Original products were preferred by patients while general practitioners preferred generic products. Conclusion Using the example of diabetes, the difference between patients' and physicians' preferences can be assessed. The use of a conjoint analysis in combination with CATI seems to be an effective approach for generation of data which are needed for policy and medical

  10. Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy.

    PubMed

    He, Bo; Zheng, Yuhuang; Liu, Meng; Zhou, Guoqiang; Chen, Xia; Mamadou, Diallo; He, Yan; Zhou, Huaying; Chen, Zi

    2013-01-01

    Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy. PMID:23434049

  11. 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

  12. 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. PMID:16133412

  13. Patient perceptions of severe COPD and transitions towards death: a qualitative study identifying milestones and developing key opportunities

    PubMed Central

    Landers, Amanda; Wiseman, Rachel; Pitama, Suzanne; Beckert, Lutz

    2015-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is a slowly disabling illness, with functional limitations and a high burden of symptoms. Palliative care services focus on quality of life for those facing life-limiting illness. Patients with COPD often see their illness as a ‘way of life’, not as a life-threatening illness, which makes the interface difficult. Aims: The aim of this study was to explore the experience of patients with advanced COPD after a life-threatening event, particularly focusing on end-of-life issues. Methods: Qualitative methods were used to capture patient experiences. Patients admitted for noninvasive ventilation for COPD were recruited and interviewed in their homes following discharge. The interview schedule explored the participants' understanding of their illness, concerns and plans, exploring end-of-life issues and perceptions of palliative care. Results: Participants were recruited until themes were saturated. Six transition points or milestones emerged: loss of recreation, home environment, episodes of acute care, long-term oxygen treatment, panic attacks, and assistance with self-care were common themes throughout the narratives. Conclusions: Milestones accumulate in no particular order. They can be easily recognised and allow health professionals to develop a common language with their patients. In advancing COPD, milestones may trigger the reassessment of goals of care and integration of a palliative approach. PMID:26158886

  14. 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.

  15. 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

  16. 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. PMID:25304102

  17. Using the Reverse Shock Index at the Injury Scene and in the Emergency Department to Identify High-Risk Patients: A Cross-Sectional Retrospective Study

    PubMed Central

    Lai, Wei-Hung; Rau, Cheng-Shyuan; Hsu, Shiun-Yuan; Wu, Shao-Chun; Kuo, Pao-Jen; Hsieh, Hsiao-Yun; Chen, Yi-Chun; Hsieh, Ching-Hua

    2016-01-01

    Background: The ratio of systolic blood pressure (SBP) to heart rate (HR), called the reverse shock index (RSI), is used to evaluate the hemodynamic stability of trauma patients. A SBP lower than the HR (RSI < 1) indicates the probability of hemodynamic shock. The objective of this study was to evaluate whether the RSI as evaluated by emergency medical services (EMS) personnel at the injury scene (EMS RSI) and the physician in the emergency department (ED RSI) could be used as an additional variable to identify patients who are at high risk of more severe injury. Methods: Data obtained from all 16,548 patients added to the trauma registry system at a Level I trauma center between January 2009 and December 2013 were retrospectively reviewed. Only patients transferred by EMS were included in this study. A total of 3715 trauma patients were enrolled and subsequently divided into four groups: group I patients had an EMS RSI ≥1 and an ED RSI ≥1 (n = 3485); group II an EMS RSI ≥ 1 and an ED RSI < 1 (n = 85); group III an EMS RSI < 1 and an ED RSI ≥ 1 (n = 98); and group IV an EMS RSI < 1 and a ED RSI < 1 (n = 47). A Pearson’s χ2 test, Fisher’s exact test, or independent Student’s t-test was conducted to compare trauma patients in groups II, III, and IV with those in group I. Results: Group II and IV patients had a higher injury severity score, a higher incidence of commonly associated injuries, and underwent more procedures (including intubation, chest tube insertion, and blood transfusion in the ED) than patients in group I. Group II and IV patients were also more likely to receive a severe injury to the thoracoabdominal area. These patients also had worse outcomes regarding the length of stay in hospital and intensive care unit (ICU), the proportion of patients admitted to ICU, and in-hospital mortality. Group II patients had a higher adjusted odds ratio for mortality (5.8-times greater) than group I patients. Conclusions: Using an RSI < 1 as a threshold

  18. Microcirculatory changes identified by photoacoustic microscopy in patients with complex regional pain syndrome type I after stellate ganglion blocks

    PubMed Central

    Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

    2014-01-01

    Abstract. Complex regional pain syndrome (CRPS) is a chronic pain syndrome that causes intractable pain, disability, and poor quality of life for patients. The etiology and pathophysiology of CRPS are still poorly understood. Due to a lack of proper diagnostic tools, the prognosis of CRPS is primarily based on clinical observation. The objective of this work is to evaluate a new imaging modality, photoacoustic microscopy (PAM), for assisting diagnoses and monitoring the progress and treatment outcome of CRPS. Blood vasculature and oxygen saturation (sO2) were imaged by PAM from eight adult patients with CRPS-1. Patients’ hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB. The results show that PAM can help diagnose and monitor CRPS. PMID:25144451

  19. Rapid 13C Urea Breath Test to Identify Helicobacter pylori Infection in Emergency Department Patients with Upper Abdominal Pain

    PubMed Central

    Meltzer, Andrew C.; Pierce, Rebecca; Cummings, Derek A.T.; Pines, Jesse M.; May, Larissa; Smith, Meaghan A.; Marcotte, Joseph; McCarthy, Melissa L.

    2013-01-01

    Introduction: In emergency department (ED) patients with upper abdominal pain, management includes ruling out serious diseases and providing symptomatic relief. One of the major causes of upper abdominal pain is an ulcer caused by Helicobacter pylori (H. pylori), which can be treated and cured with antibiotics. We sought to estimate the prevalence of H. pylori infection in symptomatic patients using a convenience sample at a single urban academic ED and demonstrate the feasibility of ED-based testing. Methods: We prospectively enrolled patients with a chief complaint of pain or discomfort in the upper abdomen for 1 year from February 2011 until February 2012 at a single academic urban ED. Enrolled subjects were tested for H. pylori using a rapid point of care 13C Urea Breath Test (UBT) [Exalenz Bioscience]. We compared patient characteristics between those who tested positive versus negative for the disease. Results: A total of 205 patients with upper abdominal pain were tested over 12 months, and 24% (95% confidence interval: 19% to 30%) tested positive for H. pylori. Black subjects were more likely to test positive than white subjects (28% v. 6%, P < 0.001). Other factors, such as age and sex, were not different between the 2 groups. Conclusion: In our ED, H. pylori infection was present in 1 in 4 patients with epigastric pain, and testing with a UBT was feasible. Further study is needed to determine the risk factors associated with infection, the prevalence of H. pylori in other EDs, the effect of the test on ED length of stay and the costeffectiveness of an ED-based test-and-treat strategy. PMID:23687549

  20. Application of a human factors classification framework for patient safety to identify precursor and contributing factors to adverse clinical incidents in hospital.

    PubMed

    Mitchell, Rebecca J; Williamson, Ann; Molesworth, Brett

    2016-01-01

    This study aimed to identify temporal precursor and associated contributing factors for adverse clinical incidents in a hospital setting using the Human Factors Classification Framework (HFCF) for patient safety. A random sample of 498 clinical incidents were reviewed. The framework identified key precursor events (PE), contributing factors (CF) and the prime causes of incidents. Descriptive statistics and correspondence analysis were used to examine incident characteristics. Staff action was the most common type of PE identified. Correspondence analysis for all PEs that involved staff action by error type showed that rule-based errors were strongly related to performing medical or monitoring tasks or the administration of medication. Skill-based errors were strongly related to misdiagnoses. Factors relating to the organisation (66.9%) or the patient (53.2%) were the most commonly identified CFs. The HFCF for patient safety was able to identify patterns of causation for the clinical incidents, highlighting the need for targeted preventive approaches, based on an understanding of how and why incidents occur. PMID:26360210

  1. Simple Prognostic Criteria can Definitively Identify Patients who Develop Severe Versus Non-Severe Dengue Disease, or Have Other Febrile Illnesses

    PubMed Central

    Falconar, Andrew K.I.; Romero-Vivas, Claudia M.E.

    2012-01-01

    Background Severe dengue disease (SDD) (DHF/DSS: dengue hemorrhagic fever/dengue shock syndrome) results from either primary or secondary dengue virus (DENV) infections, which occur 4 - 6 days after the onset of fever. As yet, there are no definitive clinical or hematological criteria that can specifically identify SDD patients during the early acute febrile-phase of disease (day 0 - 3: < 72 hours). This study was performed during a SDD (DHF/DSS) epidemic to: 1) identify the DENV serotypes that caused SDD during primary or secondary DENV infections; 2) identify simple clinical and hematological criteria that could significantly discriminate between patients who subsequently developed SDD versus non-SDD (N-SDD), or had a non-DENV fever of unknown origin (FUO) during day 0 - 3 of fever; 3) assess whether DENV serotype co-infections resulted in SDD. Methods First serum samples, with clinical and hematological criteria, were collected from 100 patients during the early acute febrile-phase (day 0 - 3: < 72 hours), assessed for DENV or FUO infections by IgM- and IgG-capture ELISAs on paired serum samples and by DENV isolations, and subsequently graded as SDD, N-SDD or FUO patients. Results In this study: 1) Thirty-three patients had DENV infections, predominantly secondary DENV-2 infections, including each SDD (DHF/DSS) case; 2) Secondary DENV-2/-3 and DENV-2/-4 serotype co-infections however resulted in N-SDD; 3) Each patient who subsequently developed SDD, but none of the others, displayed three clinical criteria: abdominal pain, conjunctival injection and veni-puncture bleeding, therefore each of these criteria provided definitively significant prognostic (P < 0.001) values; 4) Petechia, positive tourniquet tests and hepatomegaly, and neutrophilia or leukopenia also significantly identified those who: a) subsequently developed SDD versus N-SDD, or had a FUO; b) subsequently developed SDD versus N-SDD; c) subsequently developed N-SDD versus FUOs, respectively

  2. 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

  3. 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

    2016-01-01

    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. PMID:27210893

  4. 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…

  5. The dilemma of complicated shunt valves: How to identify patients with posthemorrhagic hydrocephalus after aneurysmatic subarachnoid hemorrhage who will benefit from a simple valve?

    PubMed Central

    von der Brelie, Christian; Meier, Ullrich; Gräwe, Alexander; Lemcke, Johannes

    2016-01-01

    Background: Sophisticated shunt valves provide the possibility of pressure adjustment and antisiphon control but have a higher probability of valve dysfunction especially in a posthemorrhagic setting. The aim of the present study is to analyze the clinical outcome of patients with shunt dependent posthemorrhagic hydrocephalus after aneurysmatic subarachnoid hemorrhage (SAH) in order to identify patients who would benefit from a simple differential pressure valve. Methods: From 2000 to 2013, 547 patients with aneurysmatic SAH were treated at our institution, 114 underwent ventricular shunt placement (21.1%). 47 patients with available pre- and post-operative computed tomography scans, and an available follow-up of minimum 6 months were included. In order to measure the survival time which a nonprogrammable differential pressure valve would have had in an individual patient we defined the initial equalized shunt survival time (IESS). IESS is the time until surgical revisions of fixed differential pressure or flow-regulated valves for the treatment of over- or under-drainage as well as re-programming of adjustable valves due to over- or under-drainage. Results: Twenty patients were treated with fixed differential pressure valves, 15 patients were treated with flow-regulated valves, and 12 underwent ventriculoperitoneal (VP) shunt placement with differential pressure valves assisted by a gravitational unit. Patients who reacted with remarkable changes of the ventricular width after the insertion of external ventricular drainage (EVD), before shunt placement, showed a significantly longer IESS. Conclusions: Decline of the ventricular width after EVD placement was a predictor for successful VP shunt therapy in the later course of disease. Possibly, this could allow identifying patients who benefit from a simple differential pressure valve or a flow-regulated valve, and thus could possibly avoid valve-associated complications of a programmable valve in the later course of

  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. PMID:25548667

  7. An Estimation for Availability of Battery less LF Band RFID Tag to Identify Patients in Operation Room from Viewpoint of Engineering

    NASA Astrophysics Data System (ADS)

    Hosaka, Ryosuke

    Nowadays, medical accidents increase in Japanese patient environment. Especially, misidentification of the patients occurred in operation room of higher level hospitals. It is considered that the great deals of accidents are due to mistakes by nurse. However, the accidents are prevented by management of patients. If a suitable patient identification system is developed, the accidents are prevented. In this study, new patient identification system using battery less LF band RFID(Radio Frequency Identification) is proposed. In the method, battery less RFID tag is attached to patient. In operation room, patient is identified before operation using the proposed system. However, identification distance of RFID is small. It is important that extension of the distance. In this study, antennas of RFID tag and sensor are designed. Two types of tag are proposed. One of them is set on wristband. An antenna for the tag is designed as a circular shape with 30mm in diameter. The other one is shaped like a necklace. The antenna is also designed 220mm, 240mm and 260mm in diameter. Using necklace type new antenna, sufficient identification distance for detection of the tag in the operation room is realized. The patient identification is realized using the proposed system

  8. 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

  9. Plasma Proteomic Analysis May Identify New Markers for Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer

    SciTech Connect

    Cai Xuwi; Shedden, Kerby; Ao Xiaoping; Davis, Mary

    2010-07-01

    Purpose: To study whether radiation induces differential changes in plasma proteomics in patients with and without radiation-induced lung toxicity (RILT) of Grade {>=}2 (RILT2). Methods and Materials: A total of 57 patients with NSCLC received radiation therapy (RT) were eligible. Twenty patients, 6 with RILT2 with tumor stage matched to 14 without RILT2, were enrolled for this analysis. Platelet-poor plasma was obtained before RT, at 2, 4, 6 weeks during RT, and 1 and 3 months after RT. Plasma proteomes were compared using a multiplexed quantitative proteomics approach involving ExacTag labeling, reverse-phase high-performance liquid chromatography and nano-LC electrospray tandem mass spectrometry. Variance components models were used to identify the differential protein expression between patients with and without RILT2. Results: More than 100 proteins were identified and quantified. After excluding proteins for which there were not at least 2 subjects with data for at least two time points, 76 proteins remained for this preliminary analysis. C4b-binding protein alpha chain, Complement C3, and Vitronectin had significantly higher expression levels in patients with RILT2 compared with patients without RILT2, based on both the data sets of RT start to 3 months post-RT (p < 0.01) and RT start to the end of RT (p < 0.01). The expression ratios of patients with RILT2 vs. without RILT2 were 1.60, 1.36, 1.46, and 1.66, 1.34, 1.46, for the above three proteins, respectively. Conclusions: This proteomic approach identified new plasma protein markers for future studies on RILT prediction.

  10. 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

  11. Identifying factors associated with clinical success in patients treated with NASHA®/Dx injection for fecal incontinence

    PubMed Central

    Franklin, Howard; Barrett, Andrew C; Wolf, Ray

    2016-01-01

    Purpose Injection with the bulking agent consisting of non-animal stabilized hyaluronic acid/dextranomer (NASHA®/Dx) is well tolerated and efficacious for the treatment of fecal incontinence (FI); however, the patient population that may derive maximum benefit has not been established. This post hoc responder analysis assessed demographic and baseline characteristics predictive of responsiveness to NASHA/Dx treatment. Methods Adults with a Cleveland Clinic Florida fecal incontinence score (CCFIS) ≥10 were randomized to receive NASHA/Dx or sham treatment. The primary end point was response to treatment (ie, decrease from baseline of ≥50% in number of FI episodes) at 6 months; a prespecified secondary end point was change in fecal incontinence quality of life (FIQL) score at 6 months. Post hoc subgroup analyses were performed for baseline and demographic characteristics and prior FI treatments. Results Overall, response to treatment was significantly greater with NASHA/Dx versus sham injection (52.7% vs 32.1%; P=0.0089). All subgroups analyzed demonstrated evidence of improvement, favoring NASHA/Dx versus sham treatment for both response to treatment and change in the FIQL coping/behavior subscale score. For the primary end point, a significantly greater percentage of patients with CCFIS ≤15, FI symptoms ≤5 years’ duration, or obstetric causes of FI responded to NASHA/Dx treatment versus patients receiving sham treatment (51.1% vs 28.3%, P=0.0169; 55.4% vs 25.7%, P=0.0026; and 53.6% vs 23.1%, P=0.0191, respectively). The mean change in the FIQL coping/behavior score significantly favored NASHA/Dx versus sham treatment for patients with CCFIS ≤15 (P=0.0371), FI symptoms ≤5 years’ duration (P=0.0289), or obstetric causes of FI (P=0.0384). Patients without a history of specific FI treatments (eg, antidiarrheal medications, biofeedback, surgery) were more likely to respond to NASHA/Dx versus sham treatment for both end points. Conclusion Although all

  12. A novel hemizygous SACS mutation identified by whole exome sequencing and SNP array analysis in a Chinese ARSACS patient.

    PubMed

    Liu, L; Li, X B; Zi, X H; Shen, L; Hu, Zh M; Huang, Sh X; Yu, D L; Li, H B; Xia, K; Tang, B S; Zhang, R X

    2016-03-15

    The array of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has expanded worldwide after the first description in the Charlevoix-Saguenay region of Québec. Here, we report a Chinese ARSACS patient presenting progressive peripheral neuropathy (CMTNS2=15) with horizontal gaze nystagmus and mild spastic gait. Genetic studies including whole exome sequencing (WES), Sanger sequencing and single nucleotide polymorphism (SNP) array analysis revealed a novel hemizygous nonsense mutation (c.11803C>T, p.Gln3935X) of SACS and a 1.33Mb deletion involved in SACS on chromosome 13q12.12 in the patient. Our findings highlight the necessity of SACS mutation screening in the gene panel of inherited peripheral neuropathies, and stress the need of testing copy number variation (CNV) in SACS mutation screening. PMID:26944128

  13. Identifying Engineering, Clinical and Patient's Metrics for Evaluating and Quantifying Performance of Brain-Machine Interface (BMI) Systems

    PubMed Central

    Contreras-Vidal, Jose L.

    2015-01-01

    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. PMID:26330746

  14. Ebenezer Hopkins Frost (1824-1866): William T.G. Morton's first identified patient and why he was invited to the Ether demonstration of October 16, 1846.

    PubMed

    LeVasseur, Ryan; Desai, Sukumar P

    2012-08-01

    Although he was not the first to use ether as an anesthetic, it was not until William Thomas Green Morton's demonstration of the efficacy of ether anesthesia that its use spread rapidly throughout the world. Full identities of the first anesthetized patients of William Edward Clarke and Horace Wells are not known, but we are quite certain that Crawford Williamson Long correctly identified James Venable as his first patient to receive anesthesia. Using municipal records, historical accounts, and recent analyses of Morton's unsavory side, we undertook this study to explore three questions. First, we examine how Morton refined the technique of administering anesthesia based on Wells' failed attempt. Second, we describe the circumstances under which Morton encountered his first patient to receive anesthesia. Third, we offer an explanation as to why Morton insisted on bringing along this patient to attend the grand event we celebrate as Ether Day. This is an essay about William Thomas Green Morton and Ebenezer Hopkins Frost. PMID:22728779

  15. Highly Immunoreactive IgG Antibodies Directed against a Set of Twenty Human Proteins in the Sera of Patients with Amyotrophic Lateral Sclerosis Identified by Protein Array

    PubMed Central

    May, Caroline; Nordhoff, Eckhard; Casjens, Swaantje; Turewicz, Michael; Eisenacher, Martin; Gold, Ralf; Brüning, Thomas; Pesch, Beate; Stephan, Christian; Woitalla, Dirk; Penke, Botond; Janáky, Tamás; Virók, Dezső; Siklós, László

    2014-01-01

    Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is characterized by the progressive and selective loss of upper and lower motor neurons. Diagnosis of this disorder is based on clinical assessment, and the average survival time is less than 3 years. Injections of IgG from ALS patients into mice are known to specifically mark motor neurons. Moreover, IgG has been found in upper and lower motor neurons in ALS patients. These results led us to perform a case-control study using human protein microarrays to identify the antibody profiles of serum samples from 20 ALS patients and 20 healthy controls. We demonstrated high levels of 20 IgG antibodies that distinguished the patients from the controls. These findings suggest that a panel of antibodies may serve as a potential diagnostic biomarker for ALS. PMID:24586901

  16. Incidence and predictors of pacemaker dysfunction with unipolar ventricular lead configuration. Can we identify patients who benefit from bipolar electrodes?

    PubMed

    Wiegand, U K; Bode, F; Bonnemeier, H; Tölg, R; Peters, W; Katus, H A

    2001-09-01

    Unipolar ventricular leads were implanted in a considerable percentage of pacemaker recipients. There is little information on incidence and risk factors for unipolar pacemaker dysfunction using modern lead designs. Included in a cross-sectional analysis were 682 patients who fulfilled the following criteria: chronically implanted bipolar ventricular leads (> 1 year), intraoperative stimulation threshold < 1.0 V/0.5 ms, and potential amplitude > 6 mV. Incidences of chest wall stimulation (CWS) at an output of twice the amplitude threshold and of myopotential oversensing (MPO) at a sensitivity of half the sensing threshold were assessed. Energy (0.60 [0.72] vs 0.63 [0.81] microJ) and sensing thresholds (8.31 [3.18] mV vs 8.47 [3.47] mV) did not differ between uni- and bipolar modes. While all pacemakers worked properly during bipolar configuration, malfunctions were observed in 5.9% of patients during unipolar configuration (CWS = 1.9%, MPO = 4.2%). Patient age > 76 years (hazard ratio HR 8.2; P < 0.001), heart failure > or = NYHA Class II (HR 3.8; P < 0.001), and an antiarrhythmic therapy with Class I or III drugs (HR 3.3; P = 0.002) were independently associated with the occurrence of unipolar pacemaker dysfunction. Use of steroid-eluting leads reduced the probability of pacemaker dysfunction (HR 0.45; P = 0.03). Risk factors for unipolar ventricular pacemaker malfunction were higher age, heart failure, and antiarrhythmic drug therapy. Particularly in these patients, use of bipolar ventricular leads is beneficial. PMID:11584461

  17. Network-based approach identified cell cycle genes as predictor of overall survival in lung adenocarcinoma patients.

    PubMed

    Li, Yafei; Tang, Hui; Sun, Zhifu; Bungum, Aaron O; Edell, Eric S; Lingle, Wilma L; Stoddard, Shawn M; Zhang, Mingrui; Jen, Jin; Yang, Ping; Wang, Liang

    2013-04-01

    Lung adenocarcinoma is the most common type of primary lung cancer. The purpose of this study was to delineate gene expression patterns for survival prediction in lung adenocarcinoma. Gene expression profiles of 82 (discovery set) and 442 (validation set 1) lung adenocarcinoma tumor tissues were analyzed using a systems biology-based network approach. We also examined the expression profiles of 78 adjacent normal lung tissues from 82 patients. We found a significant correlation of an expression module with overall survival (adjusted hazard ratio or HR=1.71; 95% CI=1.06-2.74 in discovery set; adjusted HR=1.26; 95% CI=1.08-1.49 in validation set 1). This expression module contained genes enriched in the biological process of the cell cycle. Interestingly, the cell cycle gene module and overall survival association were also significant in normal lung tissues (adjusted HR=1.91; 95% CI, 1.32-2.75). From these survival-related modules, we further defined three hub genes (UBE2C, TPX2, and MELK) whose expression-based risk indices were more strongly associated with poor 5-year survival (HR=3.85, 95% CI=1.34-11.05 in discovery set; HR=1.72, 95% CI=1.21-2.46 in validation set 1; and HR=3.35, 95% CI=1.08-10.04 in normal lung set). The 3-gene prognostic result was further validated using 92 adenocarcinoma tumor samples (validation set 2); patients with a high-risk gene signature have a 1.52-fold increased risk (95% CI, 1.02-2.24) of death than patients with a low-risk gene signature. These results suggest that a network-based approach may facilitate discovery of key genes that are closely linked to survival in patients with lung adenocarcinoma. PMID:23357462

  18. A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

    PubMed Central

    2010-01-01

    Background Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification. PMID:20624283

  19. Drug resistant strains of Mycobacterium tuberculosis identified through PCR-RFLP from patients of Central Punjab, Pakistan.

    PubMed

    Riaz, Muhammad; Mahmood, Zahed; Javed, Muhammad Tariq; Javed, Irum; Shahid, Muhammad; Abbas, Mazhar; Ehtisham-Ul-Haque, Syed

    2016-09-01

    The study was carried out to determine, by PCR-RFLP, the magnitude of drug resistance in Mycobacterium tuberculosis The study was carried out on 221 random sputum samples collected from patients and 120 suspected cases of drug resistance. Genetic variation in drug-resistant strains was evaluated through PCR-RFLP for isoniazid, ethambutol, streptomycin, and ofloxacin. Out of 341 patients, 91.5% were confirmed as M. tuberculosis complex infected on the basis of PCR. The random samples revealed resistance in 8.2% cases, while 73.3% of those with suspected drug resistance were found resistant. Among drug-resistant isolates, 56.1% were resistant to a single drug, 33.3% to two drugs, and 10.6% to more than two drugs. Ofloxacin resistance was observed along with isoniazid, ethambutol, and streptomycin in 6.5% cases. Resistance to isoniazid was observed in 61% cases, to ethambutol in 50.4%, and to streptomycin in 43.1% cases. It was concluded that PCR-RFLP is a useful molecular technique for the rapid detection of mutations in drug-resistant tuberculosis patients and may be used to diagnose drug resistance at the earliest. PMID:27069023

  20. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

    PubMed

    Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

    2015-07-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  1. A prediction rule to identify severe cases among adult patients hospitalized with pandemic influenza A (H1N1) 2009.

    PubMed

    Oh, Won Sup; Lee, Seung-Joon; Lee, Chang-Seop; Hur, Ji-An; Hur, Ae-Chung; Park, Yoon Seon; Heo, Sang-Taek; Bae, In-Gyu; Park, Sang Won; Kim, Eu Suk; Kim, Hong Bin; Song, Kyoung-Ho; Lee, Kkot Sil; Lee, Sang-Rok; Yeom, Joon Sup; Lee, Su Jin; Kim, Baek-Nam; Kwak, Yee Gyung; Lee, Jae Hoon; Kim, Yong Keun; Kim, Hyo Youl; Kim, Nam Joong; Oh, Myoung-Don

    2011-04-01

    The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO(2)/FiO(2) ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009. PMID:21468256

  2. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease.

    PubMed

    Wang, Yingchun; Doshi, Mona; 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-associated renal injury in allograft kidney from other etiologies. PMID:26697257

  3. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

    PubMed Central

    Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

    2016-01-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  4. Differentially expressed lncRNAs and mRNAs identified by microarray analysis in GBS patients vs healthy controls

    PubMed Central

    Xu, Jing; Gao, Chao; Zhang, Fang; Ma, Xiaofeng; Peng, Xiaolin; Zhang, Rongxin; Kong, Dexin; Simard, Alain R.; Hao, Junwei

    2016-01-01

    The aim of our present study was to determine whether message RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in patients with Guillain-Barré syndrome (GBS) compared with healthy controls. The mRNA and lncRNA profiles of GBS patients and healthy controls were generated by using microarray analysis. From microarray analysis, we listed 310 mRNAs and 114 lncRNAs with the mRMR software classed into two sample groups, GBS patients and healthy controls. KEGG mapping demonstrated that the top seven signal pathways may play important roles in GBS development. Several GO terms, such as cytosol, cellular macromolecular complex assembly, cell cycle, ligase activity, protein catabolic process, etc., were enriched in gene lists, suggesting a potential correlation with GBS development. Co-expression network analysis indicated that 113 lncRNAs and 303 mRNAs were included in the co-expression network. Our present study showed that these differentially expressed mRNAs and lncRNAs may play important roles in GBS development, which provides basic information for defining the mechanism(s) that promote GBS. PMID:26898505

  5. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients.

    PubMed

    Mori, Kentaro; Moteki, Hideaki; Miyagawa, Maiko; Nishio, Shin-Ya; Usami, Shin-Ichi

    2016-01-01

    Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500-1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434) and the total numbers of cases associated with at least one mutation was 44.07% (316/717). Among these, we were able to diagnose 212 (30%) patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8%) had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall) were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes. PMID:27627659

  6. The AFFORD Clinical Decision Aid To Identify Emergency Department Patients With Atrial Fibrillation At Low Risk For 30-Day Adverse Events

    PubMed Central

    Barrett, Tyler W.; Storrow, Alan B.; Jenkins, Cathy A.; Abraham, Robert L.; Liu, Dandan; Miller, Karen F.; Moser, Kelly M.; Russ, Stephan; Roden, Dan M.; Harrell, Frank E.; Darbar, Dawood

    2015-01-01

    There is wide variation in the management of emergency department (ED) patients with atrial fibrillation (AF). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated, tertiary-care, ED. Patients were enrolled from June 9, 2010 to February 28, 2013 and followed for 30 days. We enrolled a convenience sample of ED patients presenting with symptomatic AF. Candidate predictors were based on ED data available in the first two hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We utilized an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (<1%) patients, respectively. The decision aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement); medical history (heart failure, home sotalol use, prior percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms); ED data (2 hour heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid’s c-statistic in predicting any 30-day adverse event was 0.7 (95% CI, 0.65, 0.76). In conclusion, among ED patients with AF, AFFORD provides the first evidence based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. PMID:25633190

  7. In vitro lymphoproliferative assays with HgCl2 cannot identify patients with systemic symptoms attributed to dental amalgam.

    PubMed

    Cederbrant, K; Gunnarsson, L G; Hultman, P; Norda, R; Tibbling-Grahn, L

    1999-08-01

    Dental amalgam is suspected, by some exposed individuals, to cause various systemic psychological, sensory, and neurological symptoms. Since not all amalgam-bearers experience such reactions, an individual characteristic--for example, a susceptible immune system--might explain these conditions. In vitro lymphocyte proliferation is a valuable tool in the diagnosis of allergy. With HgCl2 as the antigen, however, the test is hampered, because Hg2+ can cause unspecific lymphocyte proliferation, optimal at 1.4 to 9.5 micrograms HgCl2/mL. Recently, the use of suboptimal HgCl2 concentrations (< or = 0.5 microgram/mL) has been suggested to circumvent these problems. The main aim of this study was to investigate whether patients with systemic symptoms alleged to result from the presence of dental amalgam differ from healthy controls, with reference to in vitro lymphoproliferative responses to HgCl2 < or = 0.5 microgram/mL. Three different test protocols--lymphocyte transformation test (LTT) in micro- and macro-cultures, and the memory lymphocyte immunostimulation assay (MELISA)--were used. Other immune parameters--such as a standard patch test for dental materials, the number of T- and B-lymphocytes, monocytes, granulocytes, and NK cells in peripheral blood, allergic symptoms, and predisposition--were also investigated. Twenty-three amalgam patients, 30 healthy blood donors with amalgam, ten healthy subjects without amalgam, and nine patients with oral lichen planus (OLP) adjacent to dental amalgam and a positive patch test to Hg0 were tested. None of the investigated immune parameters revealed any significant differences between amalgam patients and controls. The sensitivity of in vitro lymphocyte proliferation ranged from 33 to 67%, with the OLP patients as a positive control group, and the specificity from 0 to 70% for healthy controls with a negative patch test to Hg0. Thus, despite the use of HgCl2 < or = 0.5 microgram/mL, a high frequency of positive results was

  8. Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas.

    PubMed

    Caverzasi, Eduardo; Hervey-Jumper, Shawn L; Jordan, Kesshi M; Lobach, Iryna V; Li, Jing; Panara, Valentina; Racine, Caroline A; Sankaranarayanan, Vanitha; Amirbekian, Bagrat; Papinutto, Nico; Berger, Mitchel S; Henry, Roland G

    2016-07-01

    OBJECT Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection. METHODS The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery. RESULTS This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a

  9. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.

    PubMed

    Bhatnagar, Pallav; Purvis, Shirley; Barron-Casella, Emily; DeBaun, Michael R; Casella, James F; Arking, Dan E; Keefer, Jeffrey R

    2011-04-01

    Fetal hemoglobin (HbF) level has emerged as an important prognostic factor in sickle-cell disease (SCD) and can be measured by the proportion of HbF-containing erythrocytes (F-cells). Recently, BCL11A (zinc-finger protein) was identified as a regulator of HbF, and the strongest association signals were observed either directly for rs766432 or for correlated single-nucleotide polymorphisms (SNPs). To identify additional independently associated genetic variants, we performed a genome-wide association study (GWAS) on the proportion of F-cells in individuals of African ancestry with SCD from the Silent Infarct Transfusion (SIT) Trial cohort. Our study not only confirms the association of rs766432 (P-value <3.32 × 10(-13)), but also identifies an independent novel intronic SNP, rs7606173, associated with F-cells (P-value <1.81 × 10(-15)). The F-cell variances explained independently by these two SNPs are ∼13% (rs7606173) and ∼11% (rs766432), whereas, together they explain ∼16%. Additionally, in men, we identify a novel locus on chromosome 17, glucagon-like peptide-2 receptor (GLP2R), associated with F-cell regulation (rs12103880; P-value <3.41 × 10(-8)). GLP2R encodes a G protein-coupled receptor and involved in proliferative and anti-apoptotic cellular responses. These findings highlight the importance of denser genetic screens and suggest further exploration of the BCL11A and GLP2R loci to gain additional insight into HbF/F-cell regulation. PMID:21326311

  10. Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives.

    PubMed Central

    Sahmoud, T; Hoctin-Boes, G; Modigliani, R; Bitoun, A; Colombel, J F; Soule, J C; Florent, C; Gendre, J P; Lerebours, E; Sylvester, R

    1995-01-01

    No reliable identification of quiescent Crohn's disease (CD) patients with a high risk of relapse is available. The aim of this study was to develop a prognostic index to identify those patients. Untreated adult patients with quiescent disease (not induced by surgery) included in three phase III clinical trials were analysed retrospectively with respect to time to relapse. Nineteen factors related to biology, disease history, and topography were investigated. A relapse was defined as either a CD Activity Index (CDAI) > or = 200, a CDAI > or = 150 but over the baseline value by more than 100, or acute complications requiring surgery. The inclusion criteria were fulfilled by 178 patients. The median follow up was 23 months. The Cox model retained the following bad prognostic factors: age < or = 25 years, interval since first symptoms > 5 years, interval since previous relapse < or = 6 months, and colonic involvement (p < 0.001). Bootstrapping confirmed the variable selection. Patients were classified into three groups with an increasing risk of relapse (p < 0.001). The worst risk group was composed of patients presenting at least three of the four bad prognostic factors. These results make possible the design of clinical trials in quiescent CD patients with a high risk of relapse. PMID:8537053

  11. Prognosis Can Be Predicted More Accurately Using Pre- and Postchemoradiotherapy Carcinoembryonic Antigen Levels Compared to Only Prechemoradiotherapy Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer Patients Who Received Neoadjuvant Chemoradiotherapy

    PubMed Central

    Sung, SooYoon; Son, Seok Hyun; Kay, Chul Seung; Lee, Yoon Suk

    2016-01-01

    Abstract We aimed to evaluate the prognostic value of a change in the carcinoembryonic antigen (CEA) level during neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. A total of 110 patients with clinical T3/T4 or node-positive disease underwent nCRT and curative total mesorectal resection from February 2006 to December 2013. Serum CEA level was measured before nCRT, after nCRT, and then again after surgery. A cut-off value for CEA level to predict prognosis was determined using the maximally selected log-rank test. According to the test, patients were classified into 3 groups, based on their CEA levels (Group A: pre-CRT CEA ≤3.2; Group B: pre-CRT CEA level >3.2 and post-CRT CEA ≤2.8; and Group C: pre-CRT CEA >3.2 and post-CRT CEA >2.8). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) rates of Group A and Group B were similar, while Group C showed a significantly lower 3-year DFS rate (82.5% vs. 89.5% vs. 55.1%, respectively, P = 0.001). Other clinicopathological factors that showed statistical significance on univariate analysis were pre-CRT CEA, post-CRT CEA, tumor distance from the anal verge, surgery type, downstage, pathologic N stage, margin status and perineural invasion. The CEA group (P = 0.001) and tumor distance from the anal verge (P = 0.044) were significant prognostic factors for DFS on multivariate analysis. Post-CRT CEA level may be a useful prognostic factor in patients whose prognosis cannot be predicted exactly by pre-CRT CEA levels alone in the neoadjuvant treatment era. Combined pre-CRT CEA and post-CRT CEA levels enable us to predict prognosis more accurately and determine treatment and follow-up policies. Further large-scale studies are necessary to validate the prognostic value of CEA levels. PMID:26962798

  12. Accurate ab Initio Spin Densities

    PubMed Central

    2012-01-01

    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]. PMID:22707921

  13. Wide mutation spectrum and frequent variant Ala27Thr of FBN1 identified in a large cohort of Chinese patients with sporadic TAAD

    PubMed Central

    Guo, Jun; Cai, Lun; Jia, Lixin; Li, Xiaoyan; Xi, Xin; Zheng, Shuai; Liu, Xuxia; Piao, Chunmei; Liu, Tingting; Sun, Zhongsheng; Cai, Tao; Du, Jie

    2015-01-01

    Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at −1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD. PMID:26272055

  14. Diagnostic Performance of Endoscopic and Microscopic Procedures for Identifying Different Middle Ear Structures and Remaining Disease in Patients with Chronic Otitis Media: A Prospective Cohort Study

    PubMed Central

    Farahani, Farhad; Shariatpanahi, Elnaz; Jahanshahi, Javane; Poorolajal, Jalal

    2015-01-01

    Background The diagnostic performance of endoscopic and microscopic procedures for detecting diseases of the middle ear in patients with chronic otitis media (COM) has rarely been investigated. This study was conducted to compare the performance of these procedures for identifying middle ear structures and their associated diseases in COM patients. Methods In this prospective cohort study, 58 patients with chronic COM, who were candidates for tympanoplasty with or without a mastoidectomy, were enrolled. Before the surgical intervention, the middle ear was examined via an operating microscope and then through an endoscope to identify the middle ear structures as well as diseases associated with the middle ear. Results The patients were 15 years of age or older. The anatomical parts of the middle ear – the epitympanic, posterior mesotympanic, and hypotympanic structures – were more visible through an endoscope than through a microscope. In addition, the various segments of the mesotympanum, oval window, round window, and Eustachian tube were more visible via endoscopy. The post-operative endoscopic reevaluation of the middle ear revealed that a cholesteatoma had remained in four of 13 patients after surgery. Conclusion According to the results of this study, in cases in which there is poor visibility with the operating microscope or the surgeon suspects remaining disease within the middle ear, endoscopy could be utilized to improve the evaluation of more hidden middle ear pits and structures, particularly if there is a potentially recrudescent pathology. PMID:26167935

  15. 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 st