PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MotivationElectronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge.ResultsWe present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes.Availability and implementationPatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu.Supplementary informationSupplementary data are available at Bioinformatics online

Study of antioxidant activity and free radical scavenging power of Physalis alkekengi flower extract

According to the undesirable effects of many chemical preservatives in food products such as oilseed extraction industry, the possibility of substituting these materials with effective compounds of herbal plants have been considered by the researchers. In this study, at first, the Physalis Alkekengi flower extract was extracted by using maceration method with methanol. The Phenolic compounds and the amount of free radical scavenging activity of the flower extract were investigated in different concentrations (200, 400, 600, 800 and 1000 ppm), respectively by Folin–Ciocalteu method and DPPH test and were compared with the synthetic antioxidant activity (BHT) at 200 ppm. The results showed a significant difference between different concentrations of Physalis Alkekengi flower extract, in terms of the rate of Phenolic compounds and free radical scavenging activity of flower extract (p < 0.05). In general, the results of this study showed that the methanol extract of Physalis Alkekengi flower, as a source of cheap and available natural antioxidant, after conducting supplementary experiments can be used in food industry.Keywords: Physalis Alkekengi flower, Free radical scavenging power, Natural antioxidants,Phenolic compounds

Stable Knockdown of Adenosine Kinase by Lentiviral Anti-ADK miR-shRNAs in Wharton�s Jelly Stem Cells

Objective: In this study, we describe an efficient approach for stable knockdown of adenosine kinase (ADK) using lentiviral system, in an astrocytoma cell line and in human Wharton�s jelly mesenchymal stem cells (hWJMSCs). These sources of stem cells besides having multilineage differentiation potential and immunomodulatory activities, are easily available in unlimited numbers, do not raise ethical concerns and are attractive for gene manipulation and cell-based gene therapy. Materials and Methods: In this experimental study, we targeted adenosine kinase mRNA at 3' and performed coding sequences using eight miR-based expressing cassettes of anti-ADK short hairpin RNA (shRNAs). First, these cassettes with scrambled control sequences were cloned into expressing lentiviral pGIPZ vector. Quantitative real time-polymerase chain reaction (qRT-PCR) was used to screen multi-cassettes anti-ADK miR-shRNAs in stably transduced U-251 MG cell line and measuring ADK gene expression at mRNA level. Extracted WJMSCs were characterized using flow cytometry for expressing mesenchymal specific marker (CD44+) and lack of expression of hematopoietic lineage marker (CD45-). Then, the lentiviral vector that expressed the most efficient anti-ADK miR-shRNA, was employed to stably transduce WJMSCs. Results: Transfection of anti-ADK miR-shRNAs in HEK293T cells using CaPO4 method showed high efficiency. We successfully transduced U-251 cell line by recombinant lentiviruses and screened eight cassettes of anti-ADK miR-shRNAs in stably transduced U-251 MG cell line by qRT-PCR. RNAi-mediated down-regulation of ADK by lentiviral system indicated up to 95 down-regulation of ADK. Following lentiviral transduction of WJMSCs with anti-ADK miR-shRNA expression cassette, we also implicated, down-regulation of ADK up to 95 by qRT-PCR and confirmed it by western blot analysis at the protein level. Conclusion: Our findings indicate efficient usage of shRNA cassette for ADK knockdown. Engineered WJMSCs with genome editing methods like CRISPR/cas9 or more safe viral systems such as adeno-associated vectors (AAV) might be an attractive source in cell-based gene therapy and may have therapeutic potential for epilepsy

Stable Knockdown of Adenosine Kinase by Lentiviral Anti-ADK miR-shRNAs in Wharton�s Jelly Stem Cells

Objective: In this study, we describe an efficient approach for stable knockdown of adenosine kinase (ADK) using lentiviral system, in an astrocytoma cell line and in human Wharton�s jelly mesenchymal stem cells (hWJMSCs). These sources of stem cells besides having multilineage differentiation potential and immunomodulatory activities, are easily available in unlimited numbers, do not raise ethical concerns and are attractive for gene manipulation and cell-based gene therapy. Materials and Methods: In this experimental study, we targeted adenosine kinase mRNA at 3' and performed coding sequences using eight miR-based expressing cassettes of anti-ADK short hairpin RNA (shRNAs). First, these cassettes with scrambled control sequences were cloned into expressing lentiviral pGIPZ vector. Quantitative real time-polymerase chain reaction (qRT-PCR) was used to screen multi-cassettes anti-ADK miR-shRNAs in stably transduced U-251 MG cell line and measuring ADK gene expression at mRNA level. Extracted WJMSCs were characterized using flow cytometry for expressing mesenchymal specific marker (CD44+) and lack of expression of hematopoietic lineage marker (CD45-). Then, the lentiviral vector that expressed the most efficient anti-ADK miR-shRNA, was employed to stably transduce WJMSCs. Results: Transfection of anti-ADK miR-shRNAs in HEK293T cells using CaPO4 method showed high efficiency. We successfully transduced U-251 cell line by recombinant lentiviruses and screened eight cassettes of anti-ADK miR-shRNAs in stably transduced U-251 MG cell line by qRT-PCR. RNAi-mediated down-regulation of ADK by lentiviral system indicated up to 95 down-regulation of ADK. Following lentiviral transduction of WJMSCs with anti-ADK miR-shRNA expression cassette, we also implicated, down-regulation of ADK up to 95 by qRT-PCR and confirmed it by western blot analysis at the protein level. Conclusion: Our findings indicate efficient usage of shRNA cassette for ADK knockdown. Engineered WJMSCs with genome editing methods like CRISPR/cas9 or more safe viral systems such as adeno-associated vectors (AAV) might be an attractive source in cell-based gene therapy and may have therapeutic potential for epilepsy

Enoxaparin May Be Associated With Lower Rates of Mortality Than Unfractionated Heparin in Neurocritical and Surgical Patients

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), and hospital length of stay (LOS). Initially 2228 patients in the cohort were included for analysis, 1836 (82%) patients received UFH, and 392 (18%) patients received enoxaparin. After propensity score matching, a well-balanced cohort of 618 patients remained in the study (309 patients receiving UFH; 309 patients receiving enoxaparin). The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of all-cause mortality compared with enoxaparin [RR 0.73; 95% CI 0.43-1.24, p = 0.310]. There were no differences in the prevalence of DVT, prevalence of PE or hospital LOS between the two groups, DVT [RR 0.93; 95% CI 0.56-1.53, p = 0.889], PE [RR 1.50; 95% CI 0.78-2.90, p = 0.296] and LOS [9 ± 9 days vs 9 ± 8; p = 0.857]. A trend toward mortality benefit was observed in NICU [RR 0.37; 95% CI 0.13-1.07, p = 0.062] and surgical patients [RR 0.43; 95% CI 0.17-1.02, p = 0.075] favoring the enoxaparin group. The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of VTE, all-cause mortality and LOS compared to enoxaparin. In subgroup analysis, neuro-critical and surgical patients who received UFH had a higher rate of mortality than those who received enoxaparin

Validation of an internationally derived patient severity phenotype to support COVID-19 analytics from electronic health record data

ObjectiveThe Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity.Materials and methodsTwelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site.ResultsThe full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review.DiscussionWe developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions.ConclusionsWe developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites

Measurement of Family-centered care perception and parental stress in a neonatal unit

ABSTRACT Objective: to evaluate the effects of the implementation of the Patient and Family-Centered Care Model on parents and healthcare perceptions and parental stress. Method: a quasi-experimental study developed in a neonatal unit of a university hospital in the municipality of São Paulo, Brazil, with the implementation of this model of care. Data collection were performed by two sample groups, one using non-equivalent groups of parents, and another using equivalent groups of healthcare professionals. The instruments Perceptions of Family-Centered Care-Parent Brazilian Version, Perceptions of Family-Centered Care-Staff Brazilian Version and Parental Stress Scale: Neonatal Intensive Care Unit, were applied to 132 parents of newborns hospitalized and to 57 professionals. Results: there was a statistically significant improvement in the perceptions of the parents in most items assessed (p ≤0,05) and for the staff in relation to the family welcome in the neonatal unit (p = 0.041) and to the comprehension of the family's experience with the infant´s hospitalization (p = 0,050). There was a reduction in the average scores of parental stress, with a greater decrease in the Alteration in Parental Role from 4,2 to 3,8 (p = 0,048). Conclusion: the interventions improved the perceptions of parents and healthcare team related to patient and family-centered care and contributed to reducing parental stress

A Cohort Location Model of household sorting in US metropolitan regions

In this paper we propose a household sorting model for the 50 largest US metropolitan regions and evaluate the model using 2010 Census data. To approximate residential locations for household cohorts, we specify a Cohort Location Model (CLM) built upon two principle assumptions about housing consumption and metropolitan development/land use patterns. According to our model, the expected distance from the household’s residential location to the city centre(s) increases with the age of the householder (as a proxy for changes in housing career over life span). The CLM provides a flexible housing-based explanation for household sorting patterns in US metropolitan regions. Results from our analysis on US metropolitan regions show that households headed by individuals under the age of 35 are the most common cohort in centrally located areas. We also found that households over 35 are most prevalent in peripheral locations, but their sorting was not statistically different across space