Development and Implementation of an Emergent Documentation Aggression Rating Tool: Quality Improvement.

INTRODUCTION: Workplace violence is prevalent in the emergency department, putting patients and staff at risk for harm. An ED-specific standardized tool is needed to promote a consistent assessment process to strengthen documentation of escalating patient behaviors, give justification for de-escalating interventions, and reduce restraints. The purpose of this project was to design, implement, and evaluate feasibility of an ED-specific tool to help nurses proactively identify and intervene with patients' escalating behaviors, capture better documentation of aggressive/violent patient events, and reduce restraint usage. METHODS: A quality improvement design was used. The Emergent Documentation Aggression Rating Tool was constructed by combining evidence-based behavioral cues for potential aggression/violence with observed behaviors and successfully implemented interventions in patients. Nurses were trained on how to use the tool to rate patients' behaviors and take necessary action. Chart data were collected from August 2018 to December 2019 at a Midwestern suburban hospital emergency department. Chart audits and just-in-time education were conducted after implementation. Survey data were collected to evaluate nurses' perception of the tool's usefulness. RESULTS: Use of the novel Emergent Documentation Aggression Rating Tool increased over time (67.36% in Quarter 3 2018 to 97.55% in Quarter 4 2019). After Emergent Documentation Aggression Rating Tool implementation, visual inspection of the time series indicated a decrease in percent restraints, and there was an overall increase in documented escalations de-escalations over time. The patients that escalated most frequently had diagnoses of alcohol use, suicidal ideations, pain-related complaints, or mental health issues. CONCLUSION: The Emergent Documentation Aggression Rating Tool was feasible for emergency nurses to proactively identify and intervene with patients at risk for aggression/violence.

Conductive polyaniline hydrogel enhanced methane production from anaerobic wastewater treatment.

Three-dimensional polyaniline (PANI) hydrogel was used as the conductive medium to improve the methane (CH4) production from the anaerobic degradation of organics in wastewater. The porous structure and hydrophilic surface of the PANI hydrogel promoted the adhesion of the anaerobes. The PANI hydrogel existed as a conductive emeraldine base (EB) form with a conductivity of 0.42 S/cm, and had a good biocompatibility with the microorganisms in the anaerobic system. The conductive PANI hydrogel was added into the anaerobic sludge as the conductive medium of the direct interspecies electron transfer (DIET) between bacteria and archaea, accelerating CH4 production during the biodegradation of organic pollutants. The results indicated that the CH4 production rate was increased by 10.50%, 14.21%, 28.77% and 19.30% from the anaerobic system with adding 1000, 2000, 3000 and 4000 mg/L of PANI hydrogel. The proportion of Methanosaeta in the anaerobic sludge with the ability of DIET was increased to 64.74% after adding the PANI hydrogel. The conductive PANI hydrogel served as an electronic channel to enrich the microorganism with the DIET ability, which was responsible for PANI hydrogel improved CH4 production.

Bleeding, death, and costs of care during hospitalization for acute pulmonary embolism: Insights from the Saint Luke's Outcomes of Pulmonary Embolism (SLOPE) study.

Limited data exist that comprehensively describe the practical management, in-hospital outcomes, healthcare resource utilization, and rates of post-hospital readmission among patients with submassive and massive pulmonary embolism (PE). Consecutive discharges for acute PE were identified from a single health system over 3 years. Records were audited to confirm presence of acute PE, patient characteristics, disease severity, medical treatment, and PE-related invasive therapies. Rates of in-hospital major bleeding and death, hospital length of stay (LOS), direct costs, and hospital readmission are reported. From January 2016 to December 2018, 371 patients were hospitalized for acute massive or submassive PE. In-hospital major bleeding (12.1%) was common, despite low utilization of systemic thrombolysis (1.8%) or catheter-directed thrombolysis (3.0%). In-hospital death was 10-fold higher among massive PE compared to submassive PE (36.6% vs 3.3%, p < 0.001). Massive PE was more common during hospitalizations not primarily related to venous thromboembolism, including hospitalizations primarily for sepsis or infection (26.8% vs 8.2%, p = 0.001). Overall, the median LOS was 6.0 days (IQR, 3.0-11.0) and the median standardized direct cost of admissions was $10,032 (IQR, $4467-$20,330). Rates of all-cause readmission were relatively high throughout late follow-up but did not differ between PE subgroups. Despite low utilization of thrombolysis, in-hospital bleeding remains a common adverse event during hospitalizations for acute PE. Although massive PE is associated with high risk for in-hospital bleeding and death, those successfully discharged after a massive PE demonstrate similar rates of readmission compared to submassive PE into late follow-up.

Identification of Excipients for Stabilizing Fiberless Adenovirus as Biopharmaceuticals.

Reducing the promiscuous tropism of native adenovirus by using fiberless adenovirus is advantageous toward its use as a gene therapy vector or vaccine component. The removal of the fiber protein on native adenovirus abrogates several undesirable interactions; however, this approach decreases the particle's physical stability. To create stable fiberless adenovirus for pharmaceutical use, the effects of temperature and pH on the particle's stability profile must be addressed. Our results indicate that the stability of fiberless adenovirus is increased when it is stored in mildly acidic conditions around pH 6. The stability of fiberless adenovirus can be further enhanced by using excipients. Excipient screening results indicate that the nonionic surfactant Pluronic F-68 and the amino acid glycine are potential stabilizers because of their ability to increase the thermal transition temperature of the virus particle and promote retention of biological activity after exposure to prolonged thermal stress. Our data indicate that the instability of fiberless adenovirus can be ameliorated by storing the virus in the appropriate environment, and it should be possible to further optimize the virus so that it can be used as a biopharmaceutical.

Effects of cell-penetrating peptides on transduction efficiency of PEGylated adenovirus.

BACKGROUND: Adenovirus (Ad) is one of the viral vectors most widely used for gene delivery. The virus, however, has serious shortcomings such as immunogenicity, promiscuous tropism, and the inability to efficiently infect certain types of cells. The goal of this study was to improve the ability of an Ad-based vector to efficiently transform cells that lack the native coxsackie-adenovirus receptor (CAR(-)) by modifying the virus with CPP-PEG conjugates. METHODS: The vector was produced by PEGylating Ad, which packages a lacZ reporter gene, and then conjugating CPPs to form CPP-PEG-Ad particles. The study compared the effectiveness of four different CPPs: Pen, Tat, Pep1, and pArg. The effects of CPP amount per virus, degree of PEGylation, and PEG molecular weight on transduction efficiency were studied on CAR(-) NIH/3T3 cells. RESULTS: CPP-PEG-Ad particles transduced CAR(-) cells significantly better than unmodified Ad. Pen, the most effective CPP, produced an 80-fold improvement in transduction compared to the unmodified virus. The Pen peptide utilized a combination of electrostatic and hydrophobic interactions with the cell membrane to maximize cellular association while the other CPPs used only electrostatic or hydrophobic interactions but not both. Lastly, higher degrees of PEGylation, which prompted PEG to adopt a "brush" conformation, resulted in more efficient CPP-PEG-Ad particles because of both better conjugation of CPPs to the PEGylated virus and better exposure of the conjugated CPPs on the surface of the particle. CONCLUSIONS: CPP-PEG-Ad particles efficiently deliver genes to cells that Ad alone would not efficiently infect, thereby extending potential gene therapy treatments to a much broader range of cell types and diseases.

Protein impurities from cell culture dramatically impact transduction efficiency of polymer/virus hybrid vectors.

Polyethylenimine (PEI) was used recently with murine leukemia virus-like particles (MLV-VLPs) to produce a hybrid vector that possesses advantages over the native virus; the transduction efficiency of this vector, however, was less than the transduction efficiency of the native virus. The cause of the reduced efficiency was hypothesized to be related to the involvement of proteins in PEI/MLV-VLP complex formation and overall complex size. To test the hypothesis and potentially improve the efficiency of the hybrid vector, ultracentrifugation and size exclusion chromatography were used to purify MLV-VLP and to study the effect of proteins in cell culture medium on complex formation. Based on dynamic light scattering and electron microscopy, complexes formed from the purified MLV-VLPs were smaller, but surprisingly, less efficient than complexes formed from unpurified MLV-VLPs. The addition of protein to purified MLV-VLPs showed that the initial efficiency could be restored and that the purification strategy was not inactivating the MLV-VLPs. Further, by optimizing the amount of protein added to the purified MLV-VLPs, the level of transduction by PEI/MLV-VLP improved 1.6-fold. Particle characterization showed a correlation between the size of the PEI/MLV-VLP complex and the transduction efficiency, which is likely a result of greater sedimentation and cell contact during in vitro studies.

Evaluation of cell-penetrating peptide/adenovirus particles for transduction of CAR-negative cells.

Adenovirus (Ad) is a promising gene therapy vector, and is used currently in more than 23% of clinical gene therapy trials. The viral vector, however, has drawbacks such as immunogenicity, promiscuous tropism, and the inability to infect certain types of cells. The focus of this work was to develop an improved vector through electrostatic formation of a complex between negatively charged Ad and positively charged cell-penetrating peptides (CPPs), including Tat, Penetratin, polyarginine, and Pep1. The resulting complexes were demonstrated to be capable of transducing cells that lack the coxsackie-adenovirus receptor (CAR), and are otherwise difficult to infect with native Ad. The transduction efficiency of the complexes was optimized by varying the multiplicity of infection, complex formation time, and ratio of CPPs to Ad, which improved the transduction efficiency of CPP/Ad on CAR-negative cells more than 100-fold compared with unmodified Ad. The size of the CPP/Ad complex was initially less than 300 nm, but stability studies performed in the presence of serum indicate that the complex aggregates with serum after an extended period of time. The results of the current study indicate that electrostatic modification of Ad with CPPs provides a relevant platform for developing effective Ad-based gene therapy vectors.