Glenn Gobbel - Academia.edu (original) (raw)

Papers by Glenn Gobbel

Research paper thumbnail of Automating Quality Measures for Heart Failure Using Natural Language Processing: A Descriptive Study in the Department of Veterans Affairs

JMIR medical informatics, Jan 15, 2018

Background: We developed an accurate, stakeholder-informed, automated, natural language processin... more Background: We developed an accurate, stakeholder-informed, automated, natural language processing (NLP) system to measure the quality of heart failure (HF) inpatient care, and explored the potential for adoption of this system within an integrated health care system. Objective: To accurately automate a United States Department of Veterans Affairs (VA) quality measure for inpatients with HF. Methods: We automated the HF quality measure Congestive Heart Failure Inpatient Measure 19 (CHI19) that identifies whether a given patient has left ventricular ejection fraction (LVEF) <40%, and if so, whether an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was prescribed at discharge if there were no contraindications. We used documents from 1083 unique inpatients from eight VA medical centers to develop a reference standard (RS) to train (n=314) and test (n=769) the Congestive Heart Failure Information Extraction Framework (CHIEF). We also conducted semi-structured interviews (n=15) for stakeholder feedback on implementation of the CHIEF.

Research paper thumbnail of Leveraging structured and unstructured electronic health record data to detect reasons for suboptimal statin therapy use in patients with atherosclerotic cardiovascular disease

American Journal of Preventive Cardiology, 2021

Objective To determine whether natural language processing (NLP) of unstructured medical text can... more Objective To determine whether natural language processing (NLP) of unstructured medical text can improve identification of ASCVD patients not using high-intensity statin therapy (HIST) due to statin-associated side effects (SASEs) and other reasons. Methods Reviewers annotated reasons for not prescribing HIST in notes of 1152 randomly selected patients from across the VA healthcare system treated for ASCVD but not receiving HIST. Developers used reviewer annotations to train the Canary NLP tool to detect and extract notes containing one or more of these reasons. Negative predictive value (NPV), sensitivity, specificity and Area Under the Curve (AUC) were used to assess accuracy at detecting documents containing reasons when using structured data, NLP-extracted unstructured data, or both data sources combined. Results At least one documented reason for not prescribing HIST occurred in 47% of notes. The most frequent reasons were SASEs (41%) and general intolerance (20%). When identifying notes containing any documented reason for not using HIST, adding NLP-extracted, unstructured data significantly (p<0.05) increased sensitivity (0.69 (95% confidence interval [CI] 0.60–0.76) to 0.89 (95% CI 0.81–0.93)), NPV (0.90 (95% CI 0.87 to 0.93) to 0.96 (95% CI 0.93–0.98)), and AUC (0.84 (95% confidence interval [CI] 0.81–0.88) to 0.91 (95% CI 0.90–0.93)) compared to structured data alone. Conclusions NLP extraction of data from unstructured text can improve identification of reasons for patients not being on HIST over structured data alone. The additional information provided through NLP of unstructured free text should help in tailoring and implementing system-level interventions to improve HIST use in patients with ASCVD.

Research paper thumbnail of Facility Level Variation in the Reporting of Statin-Associated Side Effects Among Patients with Atherosclerotic Cardiovascular Disease

Journal of the American College of Cardiology, 2021

Research paper thumbnail of Impact of decaying dose rate in gamma knife radiosurgery: in vitro study on 9L rat gliosarcoma cells

Journal of radiosurgery and SBRT, 2012

Purpose Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corr... more Purpose Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corresponding to one two Co-60 half-lives. Between source replacements the dose rate gradually declines. The purpose of this study was to assess whether the decreasing dose rates associated with radioactive decay of Co-60 may affect the radiobiological response of a given dose delivered to 9L rat gliosarcoma cells. Method and Materials 9L rat gliosarcoma cells were irradiated using LGK U, LGK 4C, and LGK Perfexion providing three different dose rates of 0.770 Gy/ min (sources reloaded 12.0 years ago), 1.853 Gy/min (sources reloaded 5.0 years ago) and 2.937 Gy/min (sources reloaded 1.6 years ago), respectively. After irradiation of cell samples to 4.0 Gy, 8.0 Gy and 16.0 Gy using each of the LGK units, the irradiated cells were plated into petri dishes. Two weeks later cell colonies with greater than 50 cells were counted. The survival of cells was plotted as a function of dose over the range...

Research paper thumbnail of Assisted annotation of medical free text using RapTAT

Journal of the American Medical Informatics Association, 2014

Objective To determine whether assisted annotation using interactive training can reduce the time... more Objective To determine whether assisted annotation using interactive training can reduce the time required to annotate a clinical document corpus without introducing bias. Materials and methods A tool, RapTAT, was designed to assist annotation by iteratively pre-annotating probable phrases of interest within a document, presenting the annotations to a reviewer for correction, and then using the corrected annotations for further machine learning-based training before preannotating subsequent documents. Annotators reviewed 404 clinical notes either manually or using RapTAT assistance for concepts related to quality of care during heart failure treatment. Notes were divided into 20 batches of 19-21 documents for iterative annotation and training. Results The number of correct RapTAT pre-annotations increased significantly and annotation time per batch decreased by ∼50% over the course of annotation. Annotation rate increased from batch to batch for assisted but not manual reviewers. Pre-annotation F-measure increased from 0.5 to 0.6 to >0.80 (relative to both assisted reviewer and reference annotations) over the first three batches and more slowly thereafter. Overall inter-annotator agreement was significantly higher between RapTAT-assisted reviewers (0.89) than between manual reviewers (0.85). Discussion The tool reduced workload by decreasing the number of annotations needing to be added and helping reviewers to annotate at an increased rate. Agreement between the pre-annotations and reference standard, and agreement between the pre-annotations and assisted annotations, were similar throughout the annotation process, which suggests that pre-annotation did not introduce bias. Conclusions Pre-annotations generated by a tool capable of interactive training can reduce the time required to create an annotated document corpus by up to 50%.

Research paper thumbnail of Development and evaluation of RapTAT: A machine learning system for concept mapping of phrases from medical narratives

Journal of Biomedical Informatics, 2014

Rapid, automated determination of the mapping of free text phrases to pre-defined concepts could ... more Rapid, automated determination of the mapping of free text phrases to pre-defined concepts could assist in the annotation of clinical notes and increase the speed of natural language processing systems. The aim of this study was to design and evaluate a token-order-specific naïve Bayes-based machine learning system (RapTAT) to predict associations between phrases and concepts. Performance was assessed using a reference standard generated from 2860 VA discharge summaries containing 567,520 phrases that had been mapped to 12,056 distinct Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) concepts by the MCVS natural language processing system. It was also assessed on the manually annotated, 2010 i2b2 challenge data. Performance was established with regard to precision, recall, and F-measure for each of the concepts within the VA documents using bootstrapping. Within that corpus, concepts identified by MCVS were broadly distributed throughout SNOMED CT, and the token-order-specific language model achieved better performance based on precision, recall, and F-measure (0.95 ± 0.15, 0.96 ± 0.16, and 0.95 ± 0.16, respectively; mean ± SD) than the bag-of-words based, naïve Bayes model (0.64 ± 0.45, 0.61 ± 0.46, and 0.60 ± 0.45, respectively) that has previously been used for concept mapping. Precision, recall, and F-measure on the i2b2 test set were 92.9%, 85.9%, and 89.2% respectively, using the token-order-specific model. RapTAT required just 7.2 ms to map all phrases within a single discharge summary, and mapping rate did not decrease as the number of processed documents increased. The high performance attained by the tool in terms of both accuracy and speed was encouraging, and the mapping rate should be sufficient to support near-real-time, interactive annotation of medical narratives. These results demonstrate the feasibility of rapidly and accurately mapping phrases to a wide range of medical concepts based on a token-order-specific naïve Bayes model and machine learning. Published by Elsevier Inc.

Research paper thumbnail of Survival of transplanted neural progenitor cells enhanced by brain irradiation

Journal of …, 2007

HE discovery of NSCs within the adult CNS has provoked an intense and rapidly growing interest in... more HE discovery of NSCs within the adult CNS has provoked an intense and rapidly growing interest in the potential use of such cells for tissue repair and gene product delivery. 2,4,6,10,28-31,38 The interest was generated because of two important features of NSCs. First, they are multipotent and can therefore generate neurons, oligodendrocytes, and astrocytes to replace damaged tissue. Second, they are capable of self-renewal so that they can be continually expanded as a source of neurons and glia. Although there are a number of existing reports of the use of transplanted NSCs or their descendants (NPCs), authors of most studies have used either embryonic or immortalized cells. In the present study we investigate the behavior of adult rat-derived, nontransformed NPCs when implanted into allogeneic hosts. We presume that such cells will also easily implant and integrate into the brain and even track growing tumors. There have been only a few previous studies of transplantation of this form. 24,26 We also investigate the impact of various mechanical factors (such as route and method of administration) and biological factors (for example, internal milieu of host and graft tissue) on cell survival. Defining these factors and their impact is critical to the successful clinical use of cell therapy. Despite numerous reports of the amenability of the CNS to transplanted cells, no clinical trial investigating feasibility and efficacy of stem cell transplantation into the human brain has been reported. In this report, we describe the impact of cell type, delivery method, delivery site, and immunological status on the survival and integration of neural progenitors after transplantation. In addition, we report that brain irradiation before transplantation can enhance NPC integration.

Research paper thumbnail of Association of Patient, Provider and Facility Related Characteristics with Statin Associated Side Effects and Statin Use: Insight from the Veteran's Affairs Healthcare System

Journal of Clinical Lipidology

Research paper thumbnail of Facility-Level Variation in Reported Statin-Associated Side Effects Among Patients with Atherosclerotic Cardiovascular Disease—Perspective from the Veterans Affair Healthcare System

Cardiovascular Drugs and Therapy

Research paper thumbnail of Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

Pain Research and Management

Objectives. This research describes the prevalence and covariates associated with opioid-induced ... more Objectives. This research describes the prevalence and covariates associated with opioid-induced constipation (OIC) in an observational cohort study utilizing a national veteran cohort and integrated data from the Center for Medicare and Medicaid Services (CMS). Methods. A cohort of 152,904 veterans with encounters between 1 January 2008 and 30 November 2010, an exposure to opioids of 30 days or more, and no exposure in the prior year was developed to establish existing conditions and medications at the start of the opioid exposure and determining outcomes through the end of exposure. OIC was identified through additions/changes in laxative prescriptions, all-cause constipation identification through diagnosis, or constipation related procedures in the presence of opioid exposure. The association of time to constipation with opioid use was analyzed using Cox proportional hazard regression adjusted for patient characteristics, concomitant medications, laboratory tests, and comorbidit...

Research paper thumbnail of Prototype System for Detecting Interactions between Current Plant Configuration States and Component Manipulations Directed by In-Use Procedures

Research paper thumbnail of {"__content__"=>"Impact of decaying dose rate in gamma knife radiosurgery: study on 9L rat gliosarcoma cells.", "i"=>{"__content__"=>"in vitro"}}

Journal of radiosurgery and SBRT, 2012

Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years correspondin... more Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corresponding to one two Co-60 half-lives. Between source replacements the dose rate gradually declines. The purpose of this study was to assess whether the decreasing dose rates associated with radioactive decay of Co-60 may affect the radiobiological response of a given dose delivered to 9L rat gliosarcoma cells. 9L rat gliosarcoma cells were irradiated using LGK U, LGK 4C, and LGK Perfexion providing three different dose rates of 0.770 Gy/ min (sources reloaded 12.0 years ago), 1.853 Gy/min (sources reloaded 5.0 years ago) and 2.937 Gy/min (sources reloaded 1.6 years ago), respectively. After irradiation of cell samples to 4.0 Gy, 8.0 Gy and 16.0 Gy using each of the LGK units, the irradiated cells were plated into petri dishes. Two weeks later cell colonies with greater than 50 cells were counted. The survival of cells was plotted as a function of dose over the range of delivered doses and fitte...

Research paper thumbnail of Determining post-test risk in a national sample of stress nuclear myocardial perfusion imaging reports: Implications for natural language processing tools

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, Jan 25, 2018

Reporting standards promote clarity and consistency of stress myocardial perfusion imaging (MPI) ... more Reporting standards promote clarity and consistency of stress myocardial perfusion imaging (MPI) reports, but do not require an assessment of post-test risk. Natural Language Processing (NLP) tools could potentially help estimate this risk, yet it is unknown whether reports contain adequate descriptive data to use NLP. Among VA patients who underwent stress MPI and coronary angiography between January 1, 2009 and December 31, 2011, 99 stress test reports were randomly selected for analysis. Two reviewers independently categorized each report for the presence of critical data elements essential to describing post-test ischemic risk. Few stress MPI reports provided a formal assessment of post-test risk within the impression section (3%) or the entire document (4%). In most cases, risk was determinable by combining critical data elements (74% impression, 98% whole). If ischemic risk was not determinable (25% impression, 2% whole), inadequate description of systolic function (9% impress...

Research paper thumbnail of Apoptosisis induced in the subependyma of young adult rats by ionizing radiation

Clin Neurol Neurosurg, 1997

To determine if radiation-induced apoptosis occurred in young adult brain, we exposed 2-3-month o... more To determine if radiation-induced apoptosis occurred in young adult brain, we exposed 2-3-month old rats to single x-ray doses of 5 or 30 Gy. Apoptosis was quantified using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method and a morphologic assessment of nuclear fragmentation. Apoptosis occurred primarily in the subependyma but also in the corpus callosum, peaking 6 h after irradiation. At 48 h there were no apoptotic nuclei observed. These data are the first to show that apoptosis occurs in the young adult rat brain after ionizing irradiation. Further studies are required to define the particular cell type(s) involved and to address the role of this process in the pathogenesis of late radiation injury.

Research paper thumbnail of Detecting temporal expressions in medical narratives

Clinical practice and epidemiological information aggregation require knowing when, how long, and... more Clinical practice and epidemiological information aggregation require knowing when, how long, and in what sequence medically relevant events occur. The Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI) Toolkit (TTK) is a complete, open source software package for the temporal ordering of events within narrative text documents. TTK was developed on newspaper articles. We extended TTK to support medical notes using veterans&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; affairs (VA) clinical notes and compared it to TTK. We used a development set consisting of 200 VA clinical notes to modify and append rules to TTK&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s time tagger, creating Med-TTK. We then evaluated the performances of TTK and Med-TTK on an independent random selection of 100 clinical notes. Evaluation tasks were to identify and classify time-referring expressions as one of four temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this test set was generated by dual human manual review with disagreements resolved by a third reviewer. Outcome measures included recall and precision for each class, and inter-rater agreement scores. There were 3146 temporal expressions in the reference standard. TTK identified 1595 temporal expressions. Recall was 0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25-0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84-0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK. The algorithms for identifying and classifying temporal expressions in medical narratives developed within Med-TTK significantly improved performance compared to TTK. Natural language processing applications such as Med-TTK provide a foundation for meaningful longitudinal mapping of patient history events among electronic health records. The tool can be accessed at the following site: http://code.google.com/p/med-ttk/.

Research paper thumbnail of Molecular Mechanisms of DNA Damage and Repair in Ischemic Neuronal Injury

Handbook of Neurochemistry and Molecular Neurobiology, 2007

ABSTRACT Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemi... more ABSTRACT Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemic neuronal injury. The accumulation of DNA lesions, such as oxidative base damage, AP sites, and strand breaks, is an important trigger of both neuronal apoptosis and necrosis. Emerging data suggest that base excision repair (BER), the predominant mechanism for the repair of most types of oxidative DNA damage in neurons, is inducible after oxidative stress and constitutes a novel endogenous mechanism for neuroprotection. This chapter will: (1) review the importance of DNA damage in ischemic neuronal injury; (2) review the signaling pathways leading to cell death triggered by oxidative DNA damage; (3) review the DNA repair mechanisms in the brain; and (4) evaluate the importance of inducible BER as a mechanism for endogenous neuroprotection.

Research paper thumbnail of An in vivo model of DNA double strand break induction and repair after x-irradiation: The rat brain (abs)

Bellinzona, M., Hu, S., Ross, G., Gobbel, G.T., Chen, C.-Z., Deen, D.F. and Fike, J.R., 1993, An ... more Bellinzona, M., Hu, S., Ross, G., Gobbel, G.T., Chen, C.-Z., Deen, D.F. and Fike, J.R., 1993, An in vivo model of DNA double strand break induction and repair after x-irradiation: The rat brain (abs). 41st Annu. Meet. Radiat. Res. Soc. March 20-25, Dallas, Texas.

Research paper thumbnail of Age-related memory deficits in Swiss mice

Behavioral and neural biology, 1981

T h e performance of young (3-5 months) and aged (20-21 months) Swiss mice on a step-down passive... more T h e performance of young (3-5 months) and aged (20-21 months) Swiss mice on a step-down passive-avoidance task was compared in two separate experimental paradigms. Preliminary shock sensitivity testing demonstrated that response thresholds did not differ significantly between young and aged mice. Aged mice trained on a single-trial step-down procedure demonstrated significant retention deficits compared to young mice at a 24-hr training-testing interval, but not a 2-hr interval. Separate groups of mice were trained to a 180-sec criterion of avoidance and tested daily for retention over 10 days following acquisition training. Aged mice tended to step-down sooner than young animals. These data suggest agerelated retention deficits in the Swiss mouse for step-down passive avoidance without significant alterations in shock sensitivity.

Research paper thumbnail of Neuronal death is an active, caspase-dependent process after moderate but not severe DNA damage

Journal of Neurochemistry, 2001

Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults ... more Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults induce non apoptotic death, such as necrosis. The molecular targets that are damaged by these insults and ultimately induce cell death are not fully established. To determine if DNA damage can induce apoptotic or non apoptotic death depending on the severity, neurons were treated with up to 128 Gy of ionizing radiation. Such treatment induced a dose-related increase in DNA single-strand breaks but no immediate membrane disruption or lipid peroxidation. Following moderate doses of < 32 Gy, neuronal death had many characteristics of apoptosis including nuclear fragmentation and DNA laddering. Nuclear fragmentation and membrane breakdown after moderate DNA damage could be blocked by inhibition of active protein synthesis with cycloheximide and by inhibition of caspases. In contrast, cell death after doses of . 32 Gy was not blocked by cycloheximide or caspase inhibitors, and membrane breakdown occurred relatively early in the cell death process. These data suggest that cell death after high dose irradiation and severe DNA damage can occur by non apoptotic mechanisms and that blocking apoptotic pathways may not prevent death after severe damage.

Research paper thumbnail of Stereoscopic MR Imaging

Journal of Computer Assisted Tomography, 1989

The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at tw... more The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at two oblique angles imparts three-dimensional (3D) information within the projection or slice. This approach to 3D MR is rapid and straightforward, requiring only two oblique images and, at most, only a simple optical stereoscope for viewing. Stereoscopic images of the vascular system of a rat were obtained using the intravascular contrast agent albumin-(Gd-diethylenetriaminepentaacetic acid). Stereoscopic images of the human head showing CSF distribution were acquired using a long echo time sequence. These images illustrate the potential clinical applications of this technique.

Research paper thumbnail of Automating Quality Measures for Heart Failure Using Natural Language Processing: A Descriptive Study in the Department of Veterans Affairs

JMIR medical informatics, Jan 15, 2018

Background: We developed an accurate, stakeholder-informed, automated, natural language processin... more Background: We developed an accurate, stakeholder-informed, automated, natural language processing (NLP) system to measure the quality of heart failure (HF) inpatient care, and explored the potential for adoption of this system within an integrated health care system. Objective: To accurately automate a United States Department of Veterans Affairs (VA) quality measure for inpatients with HF. Methods: We automated the HF quality measure Congestive Heart Failure Inpatient Measure 19 (CHI19) that identifies whether a given patient has left ventricular ejection fraction (LVEF) <40%, and if so, whether an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was prescribed at discharge if there were no contraindications. We used documents from 1083 unique inpatients from eight VA medical centers to develop a reference standard (RS) to train (n=314) and test (n=769) the Congestive Heart Failure Information Extraction Framework (CHIEF). We also conducted semi-structured interviews (n=15) for stakeholder feedback on implementation of the CHIEF.

Research paper thumbnail of Leveraging structured and unstructured electronic health record data to detect reasons for suboptimal statin therapy use in patients with atherosclerotic cardiovascular disease

American Journal of Preventive Cardiology, 2021

Objective To determine whether natural language processing (NLP) of unstructured medical text can... more Objective To determine whether natural language processing (NLP) of unstructured medical text can improve identification of ASCVD patients not using high-intensity statin therapy (HIST) due to statin-associated side effects (SASEs) and other reasons. Methods Reviewers annotated reasons for not prescribing HIST in notes of 1152 randomly selected patients from across the VA healthcare system treated for ASCVD but not receiving HIST. Developers used reviewer annotations to train the Canary NLP tool to detect and extract notes containing one or more of these reasons. Negative predictive value (NPV), sensitivity, specificity and Area Under the Curve (AUC) were used to assess accuracy at detecting documents containing reasons when using structured data, NLP-extracted unstructured data, or both data sources combined. Results At least one documented reason for not prescribing HIST occurred in 47% of notes. The most frequent reasons were SASEs (41%) and general intolerance (20%). When identifying notes containing any documented reason for not using HIST, adding NLP-extracted, unstructured data significantly (p<0.05) increased sensitivity (0.69 (95% confidence interval [CI] 0.60–0.76) to 0.89 (95% CI 0.81–0.93)), NPV (0.90 (95% CI 0.87 to 0.93) to 0.96 (95% CI 0.93–0.98)), and AUC (0.84 (95% confidence interval [CI] 0.81–0.88) to 0.91 (95% CI 0.90–0.93)) compared to structured data alone. Conclusions NLP extraction of data from unstructured text can improve identification of reasons for patients not being on HIST over structured data alone. The additional information provided through NLP of unstructured free text should help in tailoring and implementing system-level interventions to improve HIST use in patients with ASCVD.

Research paper thumbnail of Facility Level Variation in the Reporting of Statin-Associated Side Effects Among Patients with Atherosclerotic Cardiovascular Disease

Journal of the American College of Cardiology, 2021

Research paper thumbnail of Impact of decaying dose rate in gamma knife radiosurgery: in vitro study on 9L rat gliosarcoma cells

Journal of radiosurgery and SBRT, 2012

Purpose Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corr... more Purpose Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corresponding to one two Co-60 half-lives. Between source replacements the dose rate gradually declines. The purpose of this study was to assess whether the decreasing dose rates associated with radioactive decay of Co-60 may affect the radiobiological response of a given dose delivered to 9L rat gliosarcoma cells. Method and Materials 9L rat gliosarcoma cells were irradiated using LGK U, LGK 4C, and LGK Perfexion providing three different dose rates of 0.770 Gy/ min (sources reloaded 12.0 years ago), 1.853 Gy/min (sources reloaded 5.0 years ago) and 2.937 Gy/min (sources reloaded 1.6 years ago), respectively. After irradiation of cell samples to 4.0 Gy, 8.0 Gy and 16.0 Gy using each of the LGK units, the irradiated cells were plated into petri dishes. Two weeks later cell colonies with greater than 50 cells were counted. The survival of cells was plotted as a function of dose over the range...

Research paper thumbnail of Assisted annotation of medical free text using RapTAT

Journal of the American Medical Informatics Association, 2014

Objective To determine whether assisted annotation using interactive training can reduce the time... more Objective To determine whether assisted annotation using interactive training can reduce the time required to annotate a clinical document corpus without introducing bias. Materials and methods A tool, RapTAT, was designed to assist annotation by iteratively pre-annotating probable phrases of interest within a document, presenting the annotations to a reviewer for correction, and then using the corrected annotations for further machine learning-based training before preannotating subsequent documents. Annotators reviewed 404 clinical notes either manually or using RapTAT assistance for concepts related to quality of care during heart failure treatment. Notes were divided into 20 batches of 19-21 documents for iterative annotation and training. Results The number of correct RapTAT pre-annotations increased significantly and annotation time per batch decreased by ∼50% over the course of annotation. Annotation rate increased from batch to batch for assisted but not manual reviewers. Pre-annotation F-measure increased from 0.5 to 0.6 to >0.80 (relative to both assisted reviewer and reference annotations) over the first three batches and more slowly thereafter. Overall inter-annotator agreement was significantly higher between RapTAT-assisted reviewers (0.89) than between manual reviewers (0.85). Discussion The tool reduced workload by decreasing the number of annotations needing to be added and helping reviewers to annotate at an increased rate. Agreement between the pre-annotations and reference standard, and agreement between the pre-annotations and assisted annotations, were similar throughout the annotation process, which suggests that pre-annotation did not introduce bias. Conclusions Pre-annotations generated by a tool capable of interactive training can reduce the time required to create an annotated document corpus by up to 50%.

Research paper thumbnail of Development and evaluation of RapTAT: A machine learning system for concept mapping of phrases from medical narratives

Journal of Biomedical Informatics, 2014

Rapid, automated determination of the mapping of free text phrases to pre-defined concepts could ... more Rapid, automated determination of the mapping of free text phrases to pre-defined concepts could assist in the annotation of clinical notes and increase the speed of natural language processing systems. The aim of this study was to design and evaluate a token-order-specific naïve Bayes-based machine learning system (RapTAT) to predict associations between phrases and concepts. Performance was assessed using a reference standard generated from 2860 VA discharge summaries containing 567,520 phrases that had been mapped to 12,056 distinct Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) concepts by the MCVS natural language processing system. It was also assessed on the manually annotated, 2010 i2b2 challenge data. Performance was established with regard to precision, recall, and F-measure for each of the concepts within the VA documents using bootstrapping. Within that corpus, concepts identified by MCVS were broadly distributed throughout SNOMED CT, and the token-order-specific language model achieved better performance based on precision, recall, and F-measure (0.95 ± 0.15, 0.96 ± 0.16, and 0.95 ± 0.16, respectively; mean ± SD) than the bag-of-words based, naïve Bayes model (0.64 ± 0.45, 0.61 ± 0.46, and 0.60 ± 0.45, respectively) that has previously been used for concept mapping. Precision, recall, and F-measure on the i2b2 test set were 92.9%, 85.9%, and 89.2% respectively, using the token-order-specific model. RapTAT required just 7.2 ms to map all phrases within a single discharge summary, and mapping rate did not decrease as the number of processed documents increased. The high performance attained by the tool in terms of both accuracy and speed was encouraging, and the mapping rate should be sufficient to support near-real-time, interactive annotation of medical narratives. These results demonstrate the feasibility of rapidly and accurately mapping phrases to a wide range of medical concepts based on a token-order-specific naïve Bayes model and machine learning. Published by Elsevier Inc.

Research paper thumbnail of Survival of transplanted neural progenitor cells enhanced by brain irradiation

Journal of …, 2007

HE discovery of NSCs within the adult CNS has provoked an intense and rapidly growing interest in... more HE discovery of NSCs within the adult CNS has provoked an intense and rapidly growing interest in the potential use of such cells for tissue repair and gene product delivery. 2,4,6,10,28-31,38 The interest was generated because of two important features of NSCs. First, they are multipotent and can therefore generate neurons, oligodendrocytes, and astrocytes to replace damaged tissue. Second, they are capable of self-renewal so that they can be continually expanded as a source of neurons and glia. Although there are a number of existing reports of the use of transplanted NSCs or their descendants (NPCs), authors of most studies have used either embryonic or immortalized cells. In the present study we investigate the behavior of adult rat-derived, nontransformed NPCs when implanted into allogeneic hosts. We presume that such cells will also easily implant and integrate into the brain and even track growing tumors. There have been only a few previous studies of transplantation of this form. 24,26 We also investigate the impact of various mechanical factors (such as route and method of administration) and biological factors (for example, internal milieu of host and graft tissue) on cell survival. Defining these factors and their impact is critical to the successful clinical use of cell therapy. Despite numerous reports of the amenability of the CNS to transplanted cells, no clinical trial investigating feasibility and efficacy of stem cell transplantation into the human brain has been reported. In this report, we describe the impact of cell type, delivery method, delivery site, and immunological status on the survival and integration of neural progenitors after transplantation. In addition, we report that brain irradiation before transplantation can enhance NPC integration.

Research paper thumbnail of Association of Patient, Provider and Facility Related Characteristics with Statin Associated Side Effects and Statin Use: Insight from the Veteran's Affairs Healthcare System

Journal of Clinical Lipidology

Research paper thumbnail of Facility-Level Variation in Reported Statin-Associated Side Effects Among Patients with Atherosclerotic Cardiovascular Disease—Perspective from the Veterans Affair Healthcare System

Cardiovascular Drugs and Therapy

Research paper thumbnail of Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort

Pain Research and Management

Objectives. This research describes the prevalence and covariates associated with opioid-induced ... more Objectives. This research describes the prevalence and covariates associated with opioid-induced constipation (OIC) in an observational cohort study utilizing a national veteran cohort and integrated data from the Center for Medicare and Medicaid Services (CMS). Methods. A cohort of 152,904 veterans with encounters between 1 January 2008 and 30 November 2010, an exposure to opioids of 30 days or more, and no exposure in the prior year was developed to establish existing conditions and medications at the start of the opioid exposure and determining outcomes through the end of exposure. OIC was identified through additions/changes in laxative prescriptions, all-cause constipation identification through diagnosis, or constipation related procedures in the presence of opioid exposure. The association of time to constipation with opioid use was analyzed using Cox proportional hazard regression adjusted for patient characteristics, concomitant medications, laboratory tests, and comorbidit...

Research paper thumbnail of Prototype System for Detecting Interactions between Current Plant Configuration States and Component Manipulations Directed by In-Use Procedures

Research paper thumbnail of {"__content__"=>"Impact of decaying dose rate in gamma knife radiosurgery: study on 9L rat gliosarcoma cells.", "i"=>{"__content__"=>"in vitro"}}

Journal of radiosurgery and SBRT, 2012

Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years correspondin... more Leksell Gamma Knife (LGK) installations replace their Co-60 sources every 5-10 years corresponding to one two Co-60 half-lives. Between source replacements the dose rate gradually declines. The purpose of this study was to assess whether the decreasing dose rates associated with radioactive decay of Co-60 may affect the radiobiological response of a given dose delivered to 9L rat gliosarcoma cells. 9L rat gliosarcoma cells were irradiated using LGK U, LGK 4C, and LGK Perfexion providing three different dose rates of 0.770 Gy/ min (sources reloaded 12.0 years ago), 1.853 Gy/min (sources reloaded 5.0 years ago) and 2.937 Gy/min (sources reloaded 1.6 years ago), respectively. After irradiation of cell samples to 4.0 Gy, 8.0 Gy and 16.0 Gy using each of the LGK units, the irradiated cells were plated into petri dishes. Two weeks later cell colonies with greater than 50 cells were counted. The survival of cells was plotted as a function of dose over the range of delivered doses and fitte...

Research paper thumbnail of Determining post-test risk in a national sample of stress nuclear myocardial perfusion imaging reports: Implications for natural language processing tools

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, Jan 25, 2018

Reporting standards promote clarity and consistency of stress myocardial perfusion imaging (MPI) ... more Reporting standards promote clarity and consistency of stress myocardial perfusion imaging (MPI) reports, but do not require an assessment of post-test risk. Natural Language Processing (NLP) tools could potentially help estimate this risk, yet it is unknown whether reports contain adequate descriptive data to use NLP. Among VA patients who underwent stress MPI and coronary angiography between January 1, 2009 and December 31, 2011, 99 stress test reports were randomly selected for analysis. Two reviewers independently categorized each report for the presence of critical data elements essential to describing post-test ischemic risk. Few stress MPI reports provided a formal assessment of post-test risk within the impression section (3%) or the entire document (4%). In most cases, risk was determinable by combining critical data elements (74% impression, 98% whole). If ischemic risk was not determinable (25% impression, 2% whole), inadequate description of systolic function (9% impress...

Research paper thumbnail of Apoptosisis induced in the subependyma of young adult rats by ionizing radiation

Clin Neurol Neurosurg, 1997

To determine if radiation-induced apoptosis occurred in young adult brain, we exposed 2-3-month o... more To determine if radiation-induced apoptosis occurred in young adult brain, we exposed 2-3-month old rats to single x-ray doses of 5 or 30 Gy. Apoptosis was quantified using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method and a morphologic assessment of nuclear fragmentation. Apoptosis occurred primarily in the subependyma but also in the corpus callosum, peaking 6 h after irradiation. At 48 h there were no apoptotic nuclei observed. These data are the first to show that apoptosis occurs in the young adult rat brain after ionizing irradiation. Further studies are required to define the particular cell type(s) involved and to address the role of this process in the pathogenesis of late radiation injury.

Research paper thumbnail of Detecting temporal expressions in medical narratives

Clinical practice and epidemiological information aggregation require knowing when, how long, and... more Clinical practice and epidemiological information aggregation require knowing when, how long, and in what sequence medically relevant events occur. The Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI) Toolkit (TTK) is a complete, open source software package for the temporal ordering of events within narrative text documents. TTK was developed on newspaper articles. We extended TTK to support medical notes using veterans&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; affairs (VA) clinical notes and compared it to TTK. We used a development set consisting of 200 VA clinical notes to modify and append rules to TTK&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s time tagger, creating Med-TTK. We then evaluated the performances of TTK and Med-TTK on an independent random selection of 100 clinical notes. Evaluation tasks were to identify and classify time-referring expressions as one of four temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this test set was generated by dual human manual review with disagreements resolved by a third reviewer. Outcome measures included recall and precision for each class, and inter-rater agreement scores. There were 3146 temporal expressions in the reference standard. TTK identified 1595 temporal expressions. Recall was 0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25-0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84-0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK. The algorithms for identifying and classifying temporal expressions in medical narratives developed within Med-TTK significantly improved performance compared to TTK. Natural language processing applications such as Med-TTK provide a foundation for meaningful longitudinal mapping of patient history events among electronic health records. The tool can be accessed at the following site: http://code.google.com/p/med-ttk/.

Research paper thumbnail of Molecular Mechanisms of DNA Damage and Repair in Ischemic Neuronal Injury

Handbook of Neurochemistry and Molecular Neurobiology, 2007

ABSTRACT Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemi... more ABSTRACT Oxidative DNA damage is a severe consequence of oxidative stress associated with ischemic neuronal injury. The accumulation of DNA lesions, such as oxidative base damage, AP sites, and strand breaks, is an important trigger of both neuronal apoptosis and necrosis. Emerging data suggest that base excision repair (BER), the predominant mechanism for the repair of most types of oxidative DNA damage in neurons, is inducible after oxidative stress and constitutes a novel endogenous mechanism for neuroprotection. This chapter will: (1) review the importance of DNA damage in ischemic neuronal injury; (2) review the signaling pathways leading to cell death triggered by oxidative DNA damage; (3) review the DNA repair mechanisms in the brain; and (4) evaluate the importance of inducible BER as a mechanism for endogenous neuroprotection.

Research paper thumbnail of An in vivo model of DNA double strand break induction and repair after x-irradiation: The rat brain (abs)

Bellinzona, M., Hu, S., Ross, G., Gobbel, G.T., Chen, C.-Z., Deen, D.F. and Fike, J.R., 1993, An ... more Bellinzona, M., Hu, S., Ross, G., Gobbel, G.T., Chen, C.-Z., Deen, D.F. and Fike, J.R., 1993, An in vivo model of DNA double strand break induction and repair after x-irradiation: The rat brain (abs). 41st Annu. Meet. Radiat. Res. Soc. March 20-25, Dallas, Texas.

Research paper thumbnail of Age-related memory deficits in Swiss mice

Behavioral and neural biology, 1981

T h e performance of young (3-5 months) and aged (20-21 months) Swiss mice on a step-down passive... more T h e performance of young (3-5 months) and aged (20-21 months) Swiss mice on a step-down passive-avoidance task was compared in two separate experimental paradigms. Preliminary shock sensitivity testing demonstrated that response thresholds did not differ significantly between young and aged mice. Aged mice trained on a single-trial step-down procedure demonstrated significant retention deficits compared to young mice at a 24-hr training-testing interval, but not a 2-hr interval. Separate groups of mice were trained to a 180-sec criterion of avoidance and tested daily for retention over 10 days following acquisition training. Aged mice tended to step-down sooner than young animals. These data suggest agerelated retention deficits in the Swiss mouse for step-down passive avoidance without significant alterations in shock sensitivity.

Research paper thumbnail of Neuronal death is an active, caspase-dependent process after moderate but not severe DNA damage

Journal of Neurochemistry, 2001

Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults ... more Mild insults to neurons caused by ischemia or glutamate induce apoptosis, whereas severe insults induce non apoptotic death, such as necrosis. The molecular targets that are damaged by these insults and ultimately induce cell death are not fully established. To determine if DNA damage can induce apoptotic or non apoptotic death depending on the severity, neurons were treated with up to 128 Gy of ionizing radiation. Such treatment induced a dose-related increase in DNA single-strand breaks but no immediate membrane disruption or lipid peroxidation. Following moderate doses of < 32 Gy, neuronal death had many characteristics of apoptosis including nuclear fragmentation and DNA laddering. Nuclear fragmentation and membrane breakdown after moderate DNA damage could be blocked by inhibition of active protein synthesis with cycloheximide and by inhibition of caspases. In contrast, cell death after doses of . 32 Gy was not blocked by cycloheximide or caspase inhibitors, and membrane breakdown occurred relatively early in the cell death process. These data suggest that cell death after high dose irradiation and severe DNA damage can occur by non apoptotic mechanisms and that blocking apoptotic pathways may not prevent death after severe damage.

Research paper thumbnail of Stereoscopic MR Imaging

Journal of Computer Assisted Tomography, 1989

The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at tw... more The visual fusion of two projection or slice-selective magnetic resonance (MR) images taken at two oblique angles imparts three-dimensional (3D) information within the projection or slice. This approach to 3D MR is rapid and straightforward, requiring only two oblique images and, at most, only a simple optical stereoscope for viewing. Stereoscopic images of the vascular system of a rat were obtained using the intravascular contrast agent albumin-(Gd-diethylenetriaminepentaacetic acid). Stereoscopic images of the human head showing CSF distribution were acquired using a long echo time sequence. These images illustrate the potential clinical applications of this technique.