Effectiveness of Screen-Based Simulation as a Strategy to Improve Nurse Practitioner Students' Access to Electronic Health Records in Clinical Education.

Learning to use electronic health records is essential for family nurse practitioner students to inform practice and clinical decision-making. Limited access to electronic health records during clinical training can lead to suboptimal use. Academic programs often rely on healthcare organizations to provide opportunities for students to learn electronic health record skills. However, clinical experiences are highly individualized, and students may not have access to electronic health records. Alternatives are needed to develop this critical competency. This study compared self-reported ratings regarding comfort and access to electronic health record documentation between students who participated in screen-based simulation and students who completed traditional clinical experiences with a preceptor during the last 70 hours of clinical training in one family nurse practitioner program. There was a significant difference in electronic health record access between students who participated in simulated versus traditional clinical experiences ( P = .002). There were no significant differences in ratings of comfort using electronic health records between groups. Both groups reported limited access to electronic health records in the first 500 hours of clinical experience. However, students who participated in screen-based simulation reported a quarter-fold increase in electronic health record access during their last 70 hours of clinical training.

Robust humoral immune response against rabies virus in rabbits and guinea pigs immunized with plasmid DNA vectors encoding rabies virus glycoproteins - An approach to the production of polyclonal antibody reagents.

DNA-based immunization has been previously shown to be an efficient approach to induce robust immunity against infectious diseases in animals and humans. The advantages of DNA vaccines are simplicity of their construction and production, low cost, high stability, and ability to elicit a full spectrum of immune responses to target antigens. The goals of this study were (i) to assess the antibody immune response to rabies virus glycoproteins (rGPs) in rabbits and guinea pigs after intramuscular immunization with pTargeT and pVAC2-mcs mammalian expression vectors encoding either the wild-type (WT) or codon-optimized (cOPT) rGP genes; and (ii) to prepare in-house rabbit anti-rGP polyclonal antibody reagents suitable for in Single Radial Immunodiffusion (SRID) and Indirect Fluorescent Antibody (IFA) assays. The maximum antibody responses against rabies virus in rabbits and guinea pigs were observed after immunization series with 500 µg/dose of pVAC2-mcs vector encoding either the WT or cOPT rGP genes adjuvanted with Emulsigen-D. No significant difference in the anti-rabies virus neutralizing antibody titers was observed in rabbits immunized with the WT and cOPT rGPs. The in-house rabbit anti-rGP polyclonal antibody reagents reacted comparable to the current reference reagents in SRID and IFA assays. The results of the study demonstrated that the DNA immunization of animals with the WT or cOPT rGPs is a promising approach to either induction of high anti-rabies virus neutralizing antibody titers in vivo or for production of polyclonal antibody reagents against rabies.

Achieving scientific and regulatory success in implementing non-animal approaches to human and veterinary rabies vaccine testing: A NICEATM and IABS workshop report.

This two-day workshop, co-sponsored by NICEATM and IABS-NA, brought together over 60 international scientists from government, academia, and industry to advance alternative methods for human and veterinary Rabies Virus Vaccine (RVV) potency testing. On day one, workshop presentations focused on regulatory perspectives related to in vitro potency testing, including recent additions to the European Pharmacopoeia (5.2.14) that provide a scientific rationale for why in vivo methods may be less suitable for vaccine quality control than appropriately designed in vitro methods. Further presentations reviewed the role of the consistency approach to manufacturing and vaccine batch comparison to provide supportive data for the substitution of existing animal-based methods with in vitro assays. In addition, updates from research programs evaluating and validating RVV glycoprotein (G) quantitation by ELISA as an in vitro potency test were presented. On the second day, RVV stakeholders participated in separate human and veterinary vaccine discussion groups focused on identifying potential obstacles or additional requirements for successful implementation of non-animal alternatives to the in vivo potency test. Workshop outcomes and proposed follow up activities are discussed herein.

The use of electronic health records in advanced practice nursing education: a scoping review.

Electronic health records are integral to the advanced practice registered nurse role, yet access and training during academic preparation are profoundly limited. Lack of exposure to electronic health records prevents students from becoming fully prepared for the responsibilities of clinical practice and potentially impacts quality of care, patient safety, and communication among patients and providers. This scoping review of 20 articles on electronic health record use in advanced practice registered nursing student education shows significant gaps in current research. Nine articles were classified as research. The remaining 11 were non-research reports of teaching innovations describing the use of simulated electronic health records in graduate nursing education or the use of an electronic health record in interprofessional education activities. Most of the limited research did not use valid and reliable instruments or robust designs, employed disparate approaches and tools to study the phenomenon, and measured low-level outcomes such as student navigation and confidence in using electronic health records. The non-research literature draws attention to the deficits in educational resources, including unaffordable electronic health records for academic use. Although rigorous evidence is lacking, a common theme throughout the reviewed literature was the benefit of simulation to develop electronic health record skills.

Assessment of Seroprevalence of SARS-CoV-2 and Risk Factors Associated With COVID-19 Infection Among Outpatients in Virginia.

Importance: Data from seroepidemiologic surveys measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in diverse communities and ascertaining risk factors associated with infection are important to guide future prevention strategies. Objective: To assess the prevalence of previous SARS-CoV-2 infection across Virginia and the risk factors associated with infection after the first wave of coronavirus disease 2019 (COVID-19) infections in the US. Design, Setting, and Participants: In this statewide cross-sectional surveillance study, 4675 adult outpatients presenting for health care not associated with COVID-19 in Virginia between June 1 and August 14, 2020, were recruited to participate in a questionnaire and receive venipuncture to assess SARS-CoV-2 serology. Eligibility was stratified to meet age, race, and ethnicity quotas that matched regional demographic profiles. Main Outcomes and Measures: The main outcome was SARS-CoV-2 seropositivity, as measured by the Abbott SARS-CoV-2 immunoglobulin G assay. Results: Among 4675 adult outpatients (mean [SD] age, 48.8 [16.9] years; 3119 women [66.7%]; 3098 White [66.3%] and 4279 non-Hispanic [91.5%] individuals) presenting for non-COVID-19-associated health care across Virginia, the weighted seroprevalence was 2.4% (95% CI, 1.8%-3.1%) and ranged from 0% to 20% by zip code. Seroprevalence was notably higher among participants who were Hispanic (10.2%; 95% CI, 6.1%-14.3%), residing in the northern region (4.4%; 95% CI, 2.8%-6.1%), aged 40 to 49 years (4.4%; 95% CI, 1.8%-7.1%), and uninsured (5.9%; 95% CI, 1.5%-10.3%). Higher seroprevalence was associated with Hispanic ethnicity (adjusted odds ratio [aOR], 3.56; 95% CI, 1.76-7.21), residence in a multifamily unit (aOR, 2.55; 95% CI, 1.25-5.22), and contact with an individual with confirmed COVID-19 infection (aOR, 4.33; 95% CI, 1.77-10.58). The sensitivity of serology results was 94% (95% CI, 70%-100%) among those who reported receiving a previous polymerase chain reaction test for COVID-19 infection. Among 101 participants with seropositive results, 67 individuals (66.3%) were estimated to have asymptomatic infection. These data suggested a total estimated COVID-19 burden that was 2.8-fold higher than that ascertained by PCR-positive case counts. Conclusions and Relevance: This large statewide serologic study estimated that 2.4% of adults in Virginia had exposure to SARS-CoV-2, which was 2.8-fold higher than confirmed case counts. Hispanic ethnicity, residence in a multifamily unit, and contact with an individual with confirmed COVID-19 infection were significant risk factors associated with exposure. Most infections were asymptomatic. As of August 2020, the population in Virginia remained largely immunologically naive to the virus.

A Replicable and Sustainable Whole Person Care Model for Chronic Pain.

BACKGROUND: Integrative health is an expanding field that is increasingly called upon by conventional medicine to provide care for patients with chronic pain and disease. Although evidence has mounted for delivering integrative therapies individually, there is little consensus on how best to deliver these therapies in tandem as part of whole person care. While many models exist, few are financially sustainable. METHODS AND RESULTS: This article describes a conceptual and logistical model for providing integrative outpatient health care within an academic medical center or hospital system to patients with chronic pain and disease. In hopes that the model will be replicated, administrative details are provided to explain how the model operates and has been maintained over nine years. The details include the intentional building of a particular work culture. CONCLUSION: This whole person care model that addresses chronic pain and disease in an outpatient integrative clinic has been successful, sustainable and can be replicated in other academic medical centers or hospital clinics.

SIAH and EGFR, Two RAS Pathway Biomarkers, are Highly Prognostic in Locally Advanced and Metastatic Breast Cancer.

BACKGROUND: Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS "pathway" activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine. METHODS: In this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer. FINDINGS: SIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases. INTERPRETATION: The discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy. FUNDING: This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT)-Commonwealth Research Commercialization Fund (CRCF) (MF14S-009-LS to A.H. Tang), and National Cancer Institute (CA140550 to A.H. Tang).

Targeted photodynamic therapy via receptor mediated delivery systems.

Targeted photodynamic therapy (PDT) offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. While antibody-conjugates have received the most attention, cellular transformations offer numerous other potent targets to exploit during the delivery of photosensitizers (PSs) for PDT. Alterations in receptor expression, increased levels of specific cell surface membrane lipids and proteins as well as changes in the cellular microenvironment all occur in diseased cells. Along with other biochemical and physiological changes that occur during diseased and malignant cell transformation, these factors have been utilized in order to improve the efficacy of PDT. Attempts have been made to either increase the uptake of the dye by the target cells and tissues or to improve subcellular localization so as to deliver the dye to photosensitive sites within the cells. This review discusses various PS bioconjugates that utilize these factors and summarizes the results obtained to date.

Photodynamic properties of amphiphilic derivatives of aluminum tetrasulfophthalocyanine.

Photodynamic therapy (PDT) is a promising treatment modality that has recently been accepted in clinics as a curative or palliative therapy for cancer and other nonmalignant conditions. Phthalocyanines (Pc) are attractive photosensitizers for PDT because of their enhanced photophysical and photochemical properties. The overall charge and solubility of Pc play a major role in their potential usefulness for PDT. A series of amphiphilic derivatives of tetrasulfonated aluminum Pc (AlPcS4) was prepared by substituting one of the four sulfonate groups with aliphatic side chains of 4, 8, 12 and 16 carbon atoms. The photodynamic properties of the derivatives were compared with those of AlPcS4 and the adjacent disulfonated aluminum Pc. Parameters studied included reversed-phase high-performance liquid chromatography (HPLC) retention times, capacity to generate singlet oxygen (1O2), in vitro cell uptake and phototoxicity, as well as PDT response of transplantable EMT-6 tumors in mice. The monomerized AlPcS4 derivatives showed similar or higher capacities to generate 1O2 as compared with the parent AlPcS4 as measured from relative L-tryptophan photooxidation yields. A549 cell uptake of the AlPcS4 derivatives decreased in the following order: AlPcS4(C16) > AlPcS4(C12) > AlPcS4(C8) > AlPcS4(C4). Human low-density lipoprotein at high concentrations (40 micrograms/mL) completely prevented uptake, whereas at 4 micrograms/mL uptake was decreased for the more lipophilic compounds and yet remained unaffected for the more hydrophilic dyes. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, A549 cell survival was assessed; it showed that photocytotoxic activity varied directly with the HPLC retention times, i.e. more hydrophilic compounds were less phototoxic. As 1O2 yields were similar for the four substituted AlPcS4 derivatives, it was postulated that the increased cytotoxic activity was caused by enhanced subcellular localization as a result of the long aliphatic side chains. These amphiphilic compounds proved to be photodynamically potent against the EMT-6 mouse mammary tumor model implanted in Balb/c mice. At dye doses of 0.2 mumol/kg and a fluence of 400 J/cm2 complete tumor regression was observed with no morbidity. The substitution of AlPcS4 with long aliphatic chains on the macrocycle greatly enhances its photodynamic efficacy both in vitro and in vivo.

Endothelial cell seeding of a 4-mm I.D. polyurethane vascular graft.

We evaluated the extent (luminal coverage) of the endothelial cell (EC) lining/neointimal development and the thromboresistance of electrostatically EC seeded small diameter ChronoFlex-polyurethane vascular grafts. The evaluation consisted of harvesting autologous, canine jugular vein ECs, electrostatically seeding the polyurethane grafts (4-mm I.D., length = 6 cm) with the harvested ECs, implanting the grafts in a canine femoral artery model for four to six weeks, and excising the grafts for histological and scanning electron microscopy evaluations. Results of the histological evaluation (mid-graft region only) indicated that electrostatic EC seeding led to neointimal development and to minimal to no thrombus formation within the EC seeded grafts. The unseeded control grafts resulted in no neointimal development and substantial thrombus formation on the graft luminal surfaces. Scanning electron microscopy examination demonstrated a mature, confluent endothelium with a "cobblestone" appearance on the EC seeded graft luminal surface after six weeks. We conclude that electrostatic EC seeding enhanced the development of a neointima and reduced the incidence of thrombosis in polyurethane grafts implanted in a canine femoral artery model.

Evaluation of electrostatically endothelial cell seeded expanded polytetrafluoroethylene grafts in a canine femoral artery model.

PURPOSE: The purpose of this study was to evaluate the extent (luminal coverage) of the endothelial cell (EC) lining/neointimal development and the thromboresistance of electrostatically EC seeded small diameter e-PTFE vascular grafts. METHODS: This evaluation consisted of harvesting autologous, canine jugular vein ECs, electrostatically EC seeding the e-PTFE grafts (4 mm GORE-TEX, Length = 6 cm), implanting the grafts in a canine femoral artery model for six weeks, and excising the graft for histological and scanning electron microscopy evaluations. RESULTS: The results of the histological evaluation (mid-graft region only) indicated that the electrostatic EC seeding significantly affected neointimal development (p < 0.01) and the degree of thrombus formation (p < 0.001) within the EC seeded grafts versus the untreated control grafts. Scanning electron microscopy examination demonstrated a mature, confluent endothelium with a "cobblestone" appearance on the EC seeded graft luminal surface. The control grafts demonstrated an equal distribution of SMCs through the graft wall while the electrostatically EC seeded graft sections exhibited an uneven SMC cellular distribution which was skewed toward the graft luminal surface. CONCLUSIONS: The presence of electrostatic EC seeding significantly (p < 0.01) enhanced the development of a neointima and reduced the incidence of thrombosis in e-PTFE grafts implanted in a canine femoral artery model. Results of the mid-graft SMC migration measurements indicate that the electrostatic EC seeding had a significant (p < 0.001) impact on the acute healing of the standard wall e-PTFE vascular graft specimens.

Dilemmas in providing patient-focused care.

The provision of patient-focused care to the elderly is often fraught with many ethical and challenging dilemmas. However, for health care professionals, these dilemmas can be magnified when the chronic disease is accompanied by dementia. Such was the case of Mrs. A. The multidisciplinary team of a 36-bed acute care unit identified the challenges they experienced while caring for a 65-year-old female with multiple medical problems: diabetes; hypertension; cardiovascular disease; end stage renal disease and dementia probably due to cardiovascular and metabolic causes. Mrs. A. was admitted to start hemodialysis treatments. Her care was complicated by frequent outbursts of verbal and physical aggression towards staff. Mrs. A. was deemed incapable with regard to personal care and property. Her son believed she required long-term placement, and control of her property was assumed by the Public Guardian and Trustee. Mrs. A. vehemently objected to this total loss of control. This paper will describe how the multidisciplinary team implemented a variety of strategies to help staff intervene more effectively in meeting the care needs of Mrs. A.

Optimization and qualification of a quantitative reversed-phase HPLC method for hemagglutinin in influenza preparations and its comparative evaluation with biochemical assays.

A previously described reversed-phase HPLC (RP-HPLC) method based on fast separations on a non-porous silica stationary phase [1] was optimized and qualified for the quantitative determination of hemagglutinin (HA) in influenza vaccine preparations. Optimization of the gradient elution conditions led to improved separation of the HA1 subunit from other vaccine constituents. The sensitivity of the method was significantly increased by using native fluorescence detection, resulting in an approximately 10-fold increase as compared to UV-vis detection. This enabled the elimination of the concentration step described in the original method and allowed direct analysis of vaccine preparations. The method was qualified for linearity, range, limit of detection, limit of quantitation and precision. Overall, it was found to be linear over the range of 2.5-100 µg HA/mL for all subtypes examined. This range covered 50-150% of the concentration found for individual strains in seasonal influenza vaccines and in the pandemic H1N1 vaccine. The limit of detection and limit of quantitation for each subtype were found to be suitable for the method's intended purpose and compared well to values found by the single radial immunodiffusion (SRID). The repeatability of the method gave RSD values below 5% for both retention time and peak areas. As expected for intermediate precision, larger RSD values for peak area were obtained but were below 10% and deemed acceptable. The RP-HPLC results were compared to Western blot analysis using a HA universal antibody for a set of 15 monovalent A/California H1N1 preparations and showed good correlation. Similarly, the quantitative nature of the RP-HPLC method was assessed in relation to the SRID assay currently used for the determination of the HA content in bulk antigen and final vaccine preparations. Thus, for a series of 23 monovalent A/Brisbane/59/2007 H1N1 bulks, ranging between 12.7 and 15.9 µg HA/mL by SRID, the RP-HPLC values were found to be in very good agreement, ranging between 11.9 and 14.1 µg HA/mL (n=5) for five determinations carried out on 5 different days. During the 2009-10 H1N1 influenza pandemic the quantitative RP-HPLC method was used alongside several other test methods for the analysis of pandemic H1N1 vaccine preparations that included bulk antigen and final vaccines. The HA content of vaccines formulated at 15 or 30 µg/mL was measured by RP-HPLC and SRID and results showed that the HA content determined by RP-HPLC correlated well to that determined by SRID and to values determined by Western blot. Overall, the results provided further evidence of the usefulness of RP-HPLC for the detection and quantitation of the HA content once a reference standard has been established.

Attenuation of photodynamically induced apoptosis by an RGD containing peptide.

Research efforts have focused on the improvement of already established photodynamic therapy (PDT) protocols. The use of adjunct therapies is one such route. The integrin class of receptors mediates extracellular matrix signals through a complex maze of intertwining cellular pathways. The Arg-Gly-Asp (RGD) motif is known to bind to several of the 25 known integrin receptor types. Soluble RGD peptides under most circumstances induce apoptosis in a number of cell lines In this study, the effect of an RGD-containing peptide on the photodynamic action of aluminium disulfophthalocyanine (A1PcS(2adj)) was investigated. Adenocarcinoma lung cancer cells (A549) and murine mammary cancer cells (EMT-6) were treated with A1PcS(2adj) in the presence of soluble RGD. At elevated RGD concentrations (10 mM) apoptosis was induced by the peptide alone. It was shown that at lower concentrations, RGD abrogated the apoptotic effect of PDT in both cell lines, as assessed by an MTT cytotoxicity assay, nucleosomal DNA laddering and the formation of apoptotic bodies. RGD protection against apoptosis was more pronounced in the A549 receptor positive cell line which exhibits over 70% cell survival when using 100 microM RGD peptide under LD90 conditions. Different parameters were investigated to clearly establish that the attenuation of cell killing was not solely due to quenching of the excited species by the peptide. Indeed, the phenomenon is not photophysical but biological.