Improving Time to Antibiotics for Long-Bone Open Fractures: A Quality Improvement Initiative.

ABSTRACT: Open fractures, which are exposed to the external environment, are at a high risk of infection. Administering antibiotics within 60 minutes of emergency department (ED) arrival is crucial to prevent infection. However, this is difficult to achieve due to high ED patient volumes. The purpose of our project was to improve time to antibiotics for patients presenting with long-bone open fractures at a Level 1 trauma center ED. We used the Lean Six Sigma Define, Measure, Analyze, Improve, and Control project framework to guide our efforts. Our interventions composed of developing educational initiatives, creating an electronic medical record order set, and restructuring the ED workflow to prioritize long-bone open fractures for immediate evaluation and antibiotic administration in our critical care zone. After our intervention, the time to antibiotics for long-bone open fractures improved significantly, decreasing from 76 to 40 minutes (p < .001), with the percentage of patients receiving antibiotics within 60 minutes of ED arrival increasing from 64% to 92% (p < .001). Age, sex, mechanism of injury, antibiotic choice, and location of the open fracture remained consistent between the two groups. Our results highlight the successful application of process improvement methodologies in improving antibiotic administration time for long-bone open fractures.

microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model.

Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been linked to stress reactivity, and the presence of the SERT short (S)-allele has been shown to mediate the association between maternal stress exposure and ASD. In a mouse model, we investigated the effects of prenatal stress exposure and maternal SERT genotype on offspring behavior and explored its association with maternal microRNA (miRNA) expression during pregnancy. Pregnant female mice were divided into four groups based on genotype (wildtype or SERT heterozygous knockout (Sert-het)) and the presence or absence of chronic variable stress (CVS) during pregnancy. Offspring behavior was assessed at 60 days old (PD60) using the three-chamber test, open field test, elevated plus-maze test, and marble-burying test. We found that the social preference index (SPI) of SERT-het/stress offspring was significantly lower than that of wildtype control offspring, indicating a reduced preference for social interaction on social approach, specifically for males. SERT-het/stress offspring also showed significantly more frequent grooming behavior compared to wildtype controls, specifically for males, suggesting elevated repetitive behavior. We profiled miRNA expression in maternal blood samples collected at embryonic day 21 (E21) and identified three miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) that were differentially expressed in the SERT-het/stress group compared to all other groups. These findings suggest that maternal SERT genotype and prenatal stress exposure interact to influence offspring behavior, and that maternal miRNA expression late in pregnancy may serve as a potential marker of a particular subtype of ASD pathogenesis.

Licensed Practical Nurses in Team Triage: A Safe Way to Address Nursing Shortages in the Emergency Department.

Background There is a Registered Nurse (RN) shortage across the United States that is predicted to intensify in the upcoming years. RNs are an integral part of Emergency Departments (EDs) and perform many vital tasks, including IV placement, blood draws, medication administration, acute assessments, and patient hand-offs. Thus, RN staffing is a crucial part of ED operations, and ED initiatives should account for RN workforce shortages. Given the increase in ED visits and crowding, throughput initiatives that can expedite patient care are integral to the functioning of an ED. Team Triage is a throughput initiative that has been shown to improve ED time to provider, length of stay, and left without being seen rates. In our institution, we created a Team Triage model where advanced practice providers (APPs) perform a patient's initial evaluation in triage and place orders for labs, intravenous (IV) catheters, and imaging. Given the RN staffing shortage, we incorporated Licensed Practical Nurses (LPNs) in Team Triage to place IV catheters and draw blood work for laboratory tests. The objective of this investigation was to describe a Team Triage model that incorporated LPNs and to report the patient safety and productivity of this model. Methods This was a single-site retrospective study at a large, academic, tertiary care center with over 100,000 annual visits. Adult patients who self-presented to the ED and went through Team Triage (11 am-11 pm) between Jan 1, 2020, and Jan 31, 2020, were included in this study. LPNs staffed the Team Triage, along with APPs. LPNs placed IV catheters and drew blood specimens for the Team Triage patients. The primary outcomes studied were the proportion of specimens mislabeled by LPNs, the proportion of patients receiving IV catheters, the proportion of patients receiving blood work, blood tubes drawn per hour, and IVs inserted per hour in Team Triage. Results During the study period, 1355 patients went through Team Triage. Of these patients, 1075 (79%) were ordered for blood work, and 1017 (75%) were ordered for an IV catheter. All Team Triage blood work and IV catheter placements were completed by LPNs, who staffed 372 hours of Team Triage. A total of 2558 blood tubes were collected by LPNs. The LPNs cared for 2.9 patients per hour, collected 6.9 blood tubes per hour, inserted 2.7 IV catheters per hour, and collected 2.4 blood tubes per patient. The LPNs had a 0% specimen mislabeling rate. Conclusion Due to the significant RN workforce shortage impacting Emergency Medicine coupled with increased ED crowding, there is a significant need to evaluate the integration of LPNs into Team Triage to place IV catheters and perform blood draws. This study shows that incorporating LPNs in Team Triage is a productive and safe way to address nursing shortages in Emergency Medicine.

Team triage increases discharges and decreases time to discharge without increasing test ordering.

OBJECTIVES: Emergency department (ED) crowding is detrimental to patients and staff. During traditional triage, nurses evaluate patients and identify their level of emergency. During team triage, physicians and/or nurse practitioners (NPs) and physician assistants (PAs) place orders, laboratory results, intravenous lines (IVs), and imaging in triage. Team triage improves access to testing and decreases length of stay. However, ordering practices in team triage may lead to overtesting. METHODS: This is a retrospective review of patients seen before and after a team triage process was established. Percentage of patients receiving testing and the diagnostic yields of troponins, lactates, international normalized ratios (INRs), blood cultures, glomerular filtration rates (GFR), and head computed tomography (CT) images were studied. RESULTS: A total of 704 traditionally triaged patients and 862 team triaged patients met inclusion criteria. Comparing traditional versus team triaged patients, the proportion of patients discharged was 0.44 versus 0.53 (P < 0.001), and the length of stay to discharge was 417 versus 375 minutes (P = 0.003). Comparing traditional versus team triage, a head CT was obtained 12.5% versus 5.7% (P < 0.001) of the time with diagnostic yield 45.5% versus 52% (not significant), troponin was obtained 51.3% versus 45.9% (not significant) of the time with diagnostic yield 14.9% versus 13.9% (not significant), lactate was obtained 41.6% versus 32.1% (P = 0.011) of the time with diagnostic yield 18.4% versus 12.3% (not significant), INR was obtained 70.2% versus 55.8% (P = 0.007) of the time with diagnostic yield 15.8% versus 10.5% (P = 0. 042), GFR was obtained 99.3% versus 98.4% (not significant) of the time with diagnostic yield 18.9% versus 13.7% (P = 0.02), and blood cultures were obtained 23.4% versus 7.3% (P < 0.001) of the time with diagnostic yield 7.3% versus 9.3% (not significant). CONCLUSION: Compared with traditional triage, the team triage process increased discharges and decreased time to discharge, but did not lead to increased testing or decreased diagnostic yield.

Team Triage Intervention, Including Licensed Practical Nurse, to Increase HIV Testing Rates in the Emergency Department: A Quality Improvement Project.

INTRODUCTION: Emergency departments have an important role in screening for human immunodeficiency virus infection and reducing the morbidity, mortality, and transmission of the human immunodeficiency virus. There are debates about human immunodeficiency virus screening, including opt-in, opt-out, and active choice models. Previous studies have shown that multiple factors affect the patient rate of acceptance, including where, when, and by whom the screening is offered. The purpose of this quality improvement project was to test a team-based triage intervention to improve the amount of HIV testing done in our emergency department. METHODS: The design was a single site quality improvement intervention with post-intervention monthly rates compared to historic monthly rate controls. The intervention focused on the introduction of a Licensed Practical Nurse in addition to the current triage process and personnel. The percentage of patients receiving human immunodeficiency virus testing and the number of tests sent per month before and after the implementation of the intervention were measured. RESULTS: Our results show that 0.6% (SD < 0.01) and 2.5% (SD 2.2) of patients received human immunodeficiency virus testing before and after implementation of the intervention, respectively (χ2 = 501.76, P < 0.05). A mean of 37.4 (SD = 12.91) and 151.3 (SD = 33.34) human immunodeficiency virus tests were sent per month before and after implementation of the intervention, respectively (t = 8.53, P < 0.001). DISCUSSION: This process intervention, in which licensed practical nurses offered human immunodeficiency virus screening tests during team triage, resulted in a 3-fold increase in the percentage of patients being tested for human immunodeficiency virus.

Flanking bases influence the nature of DNA distortion by platinum 1,2-intrastrand (GG) cross-links.

The differences in efficacy and molecular mechanisms of platinum anti-cancer drugs cisplatin (CP) and oxaliplatin (OX) are thought to be partially due to the differences in the DNA conformations of the CP and OX adducts that form on adjacent guanines on DNA, which in turn influence the binding of damage-recognition proteins that control downstream effects of the adducts. Here we report a comprehensive comparison of the structural distortion of DNA caused by CP and OX adducts in the TGGT sequence context using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. When compared to our previous studies in other sequence contexts, these structural studies help us understand the effect of the sequence context on the conformation of Pt-GG DNA adducts. We find that both the sequence context and the type of Pt-GG DNA adduct (CP vs. OX) play an important role in the conformation and the conformational dynamics of Pt-DNA adducts, possibly explaining their influence on the ability of many damage-recognition proteins to bind to Pt-DNA adducts.

Development of an ultraperformance liquid chromatography/mass spectrometry method to quantify cisplatin 1,2 intrastrand guanine-guanine adducts.

Platinum chemotherapeutic agents have been widely used in the treatment of cancer. Cisplatin was the first of the platinum-based chemotherapeutic agents and therefore has been extensively studied as an antitumor agent since the late 1960s. Because this agent forms several DNA adducts, a highly sensitive and specific quantitative assay is needed to correlate the molecular dose of individual adducts with the effects of treatment. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for quantification of 1,2 guanine-guanine intrastrand cisplatin adducts [CP-d(GpG)], using (15)N(10) CP-d(GpG) as an internal standard, was developed. The internal standard was characterized by MS/MS, and its concentration was validated by inductively coupled plasma mass spectrometry. Samples containing CP-d(GpG) in DNA were purified by enzyme hydrolysis, centrifugal filtration, and HPLC with fraction collection prior to quantification by UPLC-MS/MS in the selective reaction monitoring mode [m/z 412.5-->248.1 for CP-d(GpG); m/z 417.5-->253.1 for [(15)N(10)] CP-d(GpG)]. The recovery of standards was >90%, and quantification was unaffected by increasing concentrations of calf thymus DNA. This method utilizes 25 mug of DNA per injection. The limit of quantification was 3 fmol or 3.7 adducts per 10(8) nucleotides, which approaches the sensitivity of the (32)P postlabeling method for this adduct. These data suggested that this method is suitable for in vitro and in vivo assessment of CP-d(GpG) adducts formed by cisplatin and carboplatin. Subsequently, the method was applied to studies using ovarian carcinoma cell lines and C57/BL6 mice to illustrate that this method is capable of quantifying CP-d(GpG) adducts using biologically relevant systems and doses. The development of biomarkers to determine tissue-specific molecular dosimetry during treatment will lead to a more complete understanding of both therapeutic and adverse effects of cisplatin and carboplatin. This will support the refinement of therapeutic regimes and appropriate individualized treatment protocols.

The neurotoxic effects of manganese on the dopaminergic innervation of the gill of the bivalve mollusc, Crassostrea virginica.

We examined effects of manganese on the nervous system and innervation of lateral cilia of Crassostrea virginica. While essential in trace amounts, tissue manganese accumulation is neurotoxic, inducing Manganism, a Parkinson's-like disease in humans. Lateral cilia of the gill of C. virginica are controlled by a reciprocal serotonergic-dopaminergic innervation from their ganglia. Oysters were incubated 3 days in the presence of up to 1 mM manganese, followed by superfusion of the cerebral ganglia, visceral ganglia or gill with dopamine or serotonin. Beating rates of cilia were measured by stroboscopic microscopy of isolated gill preparations or gill preparations with the ipsilateral cerebral and/or visceral ganglia attached. Acute manganese treatments impaired the dopaminergic, cilio-inhibitory system, while having no effect on the serotonergic, cilio-excitatory system, which is in agreement with the proposed mechanism of manganese toxicity in humans. Manganese treatments also decreased endogenous dopamine levels in the cerebral and visceral ganglia, and gills, but not serotonin levels. We demonstrated that manganese disrupts the animal's dopaminergic system, and also that this preparation can be used to investigate mechanisms that underlie manganese neurotoxicity. It also may serve as a model in pharmacological studies of drugs to treat or prevent Manganism and other dopaminergic cell disorders.

Effects of p-Aminosalicylic acid on the Neurotoxicity of Manganese and Levels of Dopamine and Serotonin in the Nervous System and Innervated Organs of Crassostrea virginica.

Manganese is a neurotoxin causing Manganism in individuals chronically exposed to elevated levels in their environment. Toxic manganese exposure causes mental and emotional disturbances, and a movement disorder similar to Idiopathic Parkinsons Disease. Manganese interferes with dopamine neurons involved in control of body movements. Recently, p-aminosalicylic acid (PAS) is being used to alleviate symptoms of Manganism, but its mechanism of action is unknown. The eastern oyster, Crassostrea virginica, possesses a dopaminergic innervation of its gill. Oysters exposed to manganese have reduced levels of dopamine in the cerebral ganglia, visceral ganglia and gill, but not of norepinephrine, octopamine or serotonin. Those results are consistent with reported mechanisms of action of manganese in human and mammalian systems. In this study we determined the effects of PAS treatments on dopamine and serotonin levels in oysters exposed to manganese. Adult C. virginica were exposed to 500 µM and 1 mM of manganese with and without 500 µM and 1 mM of PAS by removing one shell and maintaining the animals in individual containers of aerated artificial sea water at 18° C for 3 days. Control animals were similarly treated without manganese or PAS. Dopamine and serotonin levels were measured by HPLC with fluorescence detection. PAS protected the ganglia and gill against the effects of 500 µM manganese, but not against the 1 mM manganese treatments. Serotonin levels were not affected by the treatments. The study demonstrates PAS can protect against reductions in dopamine levels caused by neurotoxic manganese exposure, but is concentration dependent. These findings may provide insights into the actions of PAS in therapeutic treatments of Manganism.

Solution structures of a DNA dodecamer duplex with and without a cisplatin 1,2-d(GG) intrastrand cross-link: comparison with the same DNA duplex containing an oxaliplatin 1,2-d(GG) intrastrand cross-link.

Proteins that discriminate between cisplatin-DNA adducts and oxaliplatin-DNA adducts are thought to be responsible for the differences in tumor range, toxicity, and mutagenicity of these two important chemotherapeutic agents. However, the structural basis for differential protein recognition of these adducts has not been determined and could be important for the design of more effective platinum anticancer agents. We have determined high-resolution NMR structures for cisplatin-GG and undamaged DNA dodecamers in the AGGC sequence context and have compared these structures with the oxaliplatin-GG structure in the same sequence context determined previously in our laboratory. This structural study allows the first direct comparison of cisplatin-GG DNA and oxaliplatin-GG DNA solution structures referenced to undamaged DNA in the same sequence context. Non-hydrogen atom rmsds of 0.81 and 1.21 were determined for the 15 lowest-energy structures for cisplatin-GG DNA and undamaged DNA, respectively, indicating good structural convergence. The theoretical NOESY spectra obtained by back-calculation from the final average structures showed excellent agreement with the experimental data, indicating that the final structures are consistent with the NMR data. Several significant conformational differences were observed between the cisplatin-GG adduct and the oxaliplatin-GG adduct, including buckle at the 5' G6.C19 base pair, opening at the 3' G7.C18 base pair, twist at the A5G6.T20C19 base pair step, slide, twist, and roll at the G6G7.C19C18 base pair step, slide at the G7C8.C18G17 base pair step, G6G7 dihedral angle, and overall bend angle. We hypothesize that these conformational differences may be related to the ability of various DNA repair proteins, DNA binding proteins, and DNA polymerases to discriminate between cisplatin-GG and oxaliplatin-GG adducts.