Development and Evaluation of an Open Source Software Tool for Deidentification of Pathology Reports

Background: Electronic medical records, including pathology reports, are often used for research purposes. Currently, there are few programs freely available to remove identifiers while leaving the remainder of the pathology report text intact. Our goal was to produce an open source, Health Insurance Portability and Accountability Act (HIPAA) compliant, deidentification tool tailored for pathology reports. We designed a three-step process for removing potential identifiers. The first step is to look for identifiers known to be associated with the patient, such as name, medical record number, pathology accession number, etc. Next, a series of pattern matches look for predictable patterns likely to represent identifying data; such as dates, accession numbers and addresses as well as patient, institution and physician names. Finally, individual words are compared with a database of proper names and geographic locations. Pathology reports from three institutions were used to design and test the algorithms. The software was improved iteratively on training sets until it exhibited good performance. 1800 new pathology reports were then processed. Each report was reviewed manually before and after deidentification to catalog all identifiers and note those that were not removed. Results: 1254 (69.7 %) of 1800 pathology reports contained identifiers in the body of the report. 3439 (98.3%) of 3499 unique identifiers in the test set were removed. Only 19 HIPAA-specified identifiers (mainly consult accession numbers and misspelled names) were missed. Of 41 non-HIPAA identifiers missed, the majority were partial institutional addresses and ages. Outside consultation case reports typically contain numerous identifiers and were the most challenging to deidentify comprehensively. There was variation in performance among reports from the three institutions, highlighting the need for site-specific customization, which is easily accomplished with our tool. Conclusion: We have demonstrated that it is possible to create an open-source deidentification program which performs well on free-text pathology reports

FTIR Measurements of Greenhouse Gases over Thessaloniki, Greece in the Framework of COCCON and Comparison with S5P/TROPOMI Observations

In this work, column-averaged dry-air mole fractions of carbon dioxide (XCO2), methane (XCH4) and carbon monoxide (XCO) are presented for the first time at a mid-latitude urban station, Thessaloniki, Greece, using the Bruker EM27/SUN ground-based low-resolution Fourier Transform spectrometer operated according to the requirements of the Collaborative Carbon Column Observing Network (COCCON). Two years of measurements are presented and examined for seasonal variability. The observed XCO2 levels show the expected seasonal cycle (spring maximum, late summer minimum) with a peak-to-peak amplitude of 12 ppm, with maximum values reported for winter 2021 exceeding 416 ppm. The XCH4 values are shown to increase in the second half of the year, with autumn showing the highest mean value of 1.878 ± 0.01 ppm. The XCO levels, following anthropogenic sources, show high winter and low summer values, exhibiting a rise again in August and September with a maximum value of 114 ± 3 ppb and a minimum in summer 2020 of 76 ± 3 ppb. Additionally, methane and carbon monoxide products obtained from the TROPOspheric Monitoring Instrument (TROPOMI), Sentinel-5P space borne sensor, are compared with the ground-based measurements. We report a good agreement between products. The relative mean bias for methane and carbon monoxide are −0.073 ± 0.647% and 3.064 ± 5.566%, respectively. Furthermore, a 15-day running average is subtracted from the original daily mean values to provide ΔXCO2, ΔXCO and ΔXCH4 residuals, so as to identify local sources at a synoptic scale. ΔXCO and ΔXCO2 show the best correlation in the winter (R2 = 0.898, slope = 0.007) season due to anthropogenic emissions in this period of the year (combustion of fossil fuels or industrial activities), while in summer no correlation is found. ΔXCO and ΔXCH4 variations are similar through both years of measurements and have a very good correlation in all seasons including winter (R2 = 0.804, slope = 1.209). The investigation of the X-gases comparison is of primary importance in order to identify local sources and quantify the impact of these trace gases to the deregulation of earth-climate system balance

Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates

PURPOSE: P-glycoprotein (Pgp) is a transmembrane drug efflux pump that is expressed in multidrug-resistant cancer cells and in a variety of normal tissues, including brain capillary endothelial cells which comprise the blood-brain barrier. We studied the effects of the Pgp inhibitor, cyclosporin A (CsA), on the cerebrospinal fluid (CSF) penetration of the Pgp substrate, doxorubicin, in non-human primates. METHODS: The animals received doxorubicin alone (2.0 mg/kg i.v. over 60 min) or doxorubicin (1 mg/kg i.v. over 60 min) and CsA (loading dose 4.0 mg/kg i.v. over 2 h, followed by continuous infusion of 12 mg/kg per day over 48 h). Plasma and CSF were collected over 48 h and the doxorubicin concentration was measured by reverse-phase high-pressure liquid chromatography (HPLC) with fluorescence detection (detection limit 5 nM). A two-compartment model was fitted to the plasma concentration-time data. RESULTS: Pgp was demonstrated to be present in the epithelium of the choroid plexus by immunohistochemical methods, indicating that CSF drug penetration could be used as a surrogate for blood-brain barrier penetration. Steady state whole blood CsA concentrations, which were measured with a fluorescence-polarization immunoassay (TDX) that detects both CsA and its metabolites, ranged from 551-1315 microg/l at 24 h. The clearance of doxorubicin in four animals was reduced by 34%, 38%, 45% and 49% when given with CsA. The doxorubicin concentration in the CSF was <5 nM in all animals, both after doxorubicin alone and doxorubicin with CsA. CONCLUSIONS: The Pgp inhibitor, CsA, at a concentration that alters systemic clearance of doxorubicin, does not appear to significantly increase the CSF penetration of doxorubicin

First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children’s Oncology Group Phase 1/Pilot Consortium

Characterize the pharmacokinetics of oral crizotinib in children with cancer

Development and evaluation of an open source software tool for deidentification of pathology reports

BACKGROUND: Electronic medical records, including pathology reports, are often used for research purposes. Currently, there are few programs freely available to remove identifiers while leaving the remainder of the pathology report text intact. Our goal was to produce an open source, Health Insurance Portability and Accountability Act (HIPAA) compliant, deidentification tool tailored for pathology reports. We designed a three-step process for removing potential identifiers. The first step is to look for identifiers known to be associated with the patient, such as name, medical record number, pathology accession number, etc. Next, a series of pattern matches look for predictable patterns likely to represent identifying data; such as dates, accession numbers and addresses as well as patient, institution and physician names. Finally, individual words are compared with a database of proper names and geographic locations. Pathology reports from three institutions were used to design and test the algorithms. The software was improved iteratively on training sets until it exhibited good performance. 1800 new pathology reports were then processed. Each report was reviewed manually before and after deidentification to catalog all identifiers and note those that were not removed. RESULTS: 1254 (69.7 %) of 1800 pathology reports contained identifiers in the body of the report. 3439 (98.3%) of 3499 unique identifiers in the test set were removed. Only 19 HIPAA-specified identifiers (mainly consult accession numbers and misspelled names) were missed. Of 41 non-HIPAA identifiers missed, the majority were partial institutional addresses and ages. Outside consultation case reports typically contain numerous identifiers and were the most challenging to deidentify comprehensively. There was variation in performance among reports from the three institutions, highlighting the need for site-specific customization, which is easily accomplished with our tool. CONCLUSION: We have demonstrated that it is possible to create an open-source deidentification program which performs well on free-text pathology reports

Haptoglobin Gene Expression and Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A COG-ALTE03N1 Report

Article describes how anthracycline-related cardiomyopathy is a leading cause of premature death in childhood cancer survivors. The authors interrogated differentially expressed genes (DEGs) to identify genetic variants serving regulatory functions or genetic variants not easily identified when using genomewide array platforms

Synaptic and Intrinsic Activation of GABAergic Neurons in the Cardiorespiratory Brainstem Network

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in close apposition to cardioinhibitory parasympathetic cardiac neurons in the nucleus ambiguus (NA). These neurons fire in synchronization with inspiratory activity. Although they receive excitatory glutamatergic synaptic inputs during inspiration, this excitatory neurotransmission was not altered by blocking nicotinic receptors, and many of these GABAergic neurons continue to fire after synaptic blockade. The spontaneous firing in these GABAergic neurons was not altered by the voltage-gated calcium channel blocker cadmium chloride that blocks both neurotransmission to these neurons and voltage-gated Ca2+ currents, but spontaneous firing was diminished by riluzole, demonstrating a role of persistent sodium channels in the spontaneous firing in these cardiorespiratory GABAergic neurons that possess a pacemaker phenotype. The spontaneously firing GABAergic neurons identified in this study that increase their activity during inspiration would support respiratory rhythm generation if they acted primarily to inhibit post-inspiratory neurons and thereby release inspiration neurons to increase their activity. This population of inspiratory-modulated GABAergic neurons could also play a role in inhibiting neurons that are most active during expiration and provide a framework for respiratory sinus arrhythmia as there is an increase in heart rate during inspiration that occurs via inhibition of premotor parasympathetic cardioinhibitory neurons in the NA during inspiration