The impact on thirty day readmissions for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease admitted to an observation unit versus an inpatient medical unit: A retrospective observational study.

OBJECTIVES: We aimed to evaluate the utility of an Observation Unit (OU) in management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and to identify the clinical characteristics of patients readmitted within 30-days for AECOPD following index admission to the OU or inpatient floor from the OU. METHODS: This is a retrospective observational study of patients admitted from January to December 2017 for AECOPD to an OU in an urban-based tertiary care hospital. Primary outcome was rate of 30-day readmission after admission for AECOPD for patients discharged from the OU versus inpatient service after failing OU management. Regression analyses were used to define risk factors. RESULTS: 163 OU encounters from 92 unique patients were included. There was a lower readmission rate (33%) for patients converted from OU to inpatient care versus patients readmitted after direct discharge from the OU (44%). Patients with 30-day readmissions were more likely to be undomiciled, with history of congestive heart failure (CHF), pulmonary embolism (PE), or had previous admissions for AECOPD. Patients with >6 annual OU visits for AECOPD had higher rates of substance abuse, psychiatric diagnosis, and prior PE; when these patients were excluded, the 30-day readmission rate decreased to 13.5%. CONCLUSION: Patients admitted for AECOPD with a history of PE, CHF, prior AECOPD admissions, and socioeconomic deprivation are at higher risk of readmission and should be prioritized for direct inpatient admission. Further prospective studies should be conducted to determine the clinical impact of this approach on readmission rates.

Predicting Impact of Prone Position on Oxygenation in Mechanically Ventilated Patients with COVID-19.

OBJECTIVES: Prone positioning is widely used in mechanically ventilated patients with COVID-19; however, the specific clinical scenario in which the individual is most poised to benefit is not fully established. In patients with COVID-19 respiratory failure requiring mechanical ventilation, how effective is prone positioning in improving oxygenation and can that response be predicted? DESIGN: This is a retrospective observational study from two tertiary care centers including consecutive patients mechanically ventilated for COVID-19 from 3/1/2020 - 7/1/2021. The primary outcome is improvement in oxygenation as measured by PaO2/FiO2. We describe oxygenation before, during and after prone episodes with a focus on identifying patient, respiratory or ventilator variables that predict prone positioning success. SETTING: 2 Tertiary Care Academic Hospitals. PATIENTS: 125 patients mechanically ventilated for COVID-19 respiratory failure. INTERVENTIONS: Prone positioning. MAIN RESULTS: One hundred twenty-five patients underwent prone positioning a total of 309 times for a median duration of 23 hours IQR (14 - 49). On average, PaO2/FiO2 improved 19%: from 115 mm Hg (80 - 148) immediately before proning to 137 mm Hg (95 - 197) immediately after returning to the supine position. Prone episodes were more successful if the pre-prone PaO2/FiO2 was lower and if the patient was on inhaled epoprostenol (iEpo). For individuals with severe acute respiratory distress syndrome (ARDS) (PaO2/FiO2 < 100 prior to prone positioning) and on iEpo, the median improvement in PaO2/FiO2 was 27% in both instances. CONCLUSIONS: Prone positioning in mechanically ventilated patients with COVID-19 is generally associated with sustained improvements in oxygenation, which is made more likely by the concomitant use of iEpo and is more impactful in those who are more severely hypoxemic prior to prone positioning.

The Impact of a Comprehensive Simulation-Based Training and Certification Program on Resident Central Venous Catheter Complication Rates.

INTRODUCTION: Millions of central venous catheters (CVCs) are placed annually in the United States, many by resident physicians. Simulation training has been proposed as a means to increase resident physician competence with CVC placement and decrease the incidence of line-associated mechanical complications. We aimed to evaluate the impact of a novel simulation-based CVC training program for resident physicians on CVC-associated mechanical complication rates. We hypothesized that the CVC-related mechanical complication rates would be lower among simulation-trained residents (STRs) compared with nonsimulation, traditionally trained residents (TTRs). METHODS: A retrospective chart review was performed of patients with a CVC placed by a resident physician between October 2014 and January 2017 at MedStar Georgetown University Hospital in Washington, DC. Incidence of CVC mechanical complications, including pneumothorax, hemothorax, arterial injury, or retained guidewire, were extracted from the electronic medical record and compared between STR and TTR cohorts. In contrast to TTRs who were trained to place CVCs in a supervised clinical setting, STRs underwent a CVC training program using online modules, a hands-on simulation training and testing checklist, and a series of successful supervised insertions before being credentialed to place lines independently. RESULTS: Nine hundred twenty-four CVCs placed by resident physicians during the study period were analyzed. There was no statistically significant difference in total mechanical complication rates between the STRs and TTRs in this study period (2.4% vs. 2.2%, P = 1). Simulation-trained residents were more likely to use ultrasound guidance when indicated during CVC insertion compared with TTRs (94.8% vs. 70.5%, P < 0.001). CONCLUSIONS: Mechanical complication rates associated with CVC insertion were similar between the simulation and TTRs and were consistent with previously published literature. These findings suggest that residents who underwent simulation training and certification demonstrated performance on par with more experienced TTRs. In addition, they were more likely to use best practices including ultrasound guidance in line placement.

Pharmacist Interventions to Improve Specialty Medication Adherence: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: The effectiveness of specialty medications in complicated clinical conditions depends on adherence to therapy. However, specialty medications pose unique barriers to adherence. OBJECTIVE: This study aims to determine whether pharmacist interventions improve specialty medication adherence. METHODS: This is a single-center, pragmatic, randomized controlled trial ongoing since 10 May 2019 at an integrated health system specialty pharmacy. This study evaluates usual care compared with usual care plus patient-tailored adherence interventions. Study design and procedures were informed by focus groups with patients and specialty pharmacists. Patients at Vanderbilt Specialty Pharmacy with a proportion of days covered (PDC) < 90% in the previous 4 months are identified by a daily query of the electronic pharmacy database. A pharmacist reviews these patients' electronic health records to identify and exclude ineligible patients. Eligible patients are randomized evenly to the control or intervention arm and stratified by historical clinic nonadherence rates. Patients randomized to the intervention arm undergo a baseline assessment to clarify reasons for nonadherence and subsequently receive patient-tailored interventions based on their specific reasons. Interventions and follow-up are provided at the discretion of the intervening pharmacist. The primary outcome is PDC calculated at 8 months post-enrollment. Enrollment of 438 participants will provide 90% power to detect a 5% difference in PDC between the two arms within each nonadherence risk stratum. DISCUSSION: This trial will evaluate the effect of patient-tailored interventions on specialty medication adherence and will inform how often and why patients are misidentified as nonadherent. REGISTRATION: The trial was deemed a quality improvement initiative by the Vanderbilt University Institutional Review Board. It was registered in ClinicalTrials.gov (NCT03709277) on 17 October 2018.

Pharmacist Interventions to Improve Specialty Medication Adherence: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: The effectiveness of specialty medications in complicated clinical conditions depends on adherence to therapy. However, specialty medications pose unique barriers to adherence. OBJECTIVE: This study aims to determine whether pharmacist interventions improve specialty medication adherence. METHODS: This is a single-center, pragmatic, randomized controlled trial ongoing since 10 May 2019 at an integrated health system specialty pharmacy. This study evaluates usual care compared with usual care plus patient-tailored adherence interventions. Study design and procedures were informed by focus groups with patients and specialty pharmacists. Patients at Vanderbilt Specialty Pharmacy with a proportion of days covered (PDC) < 90% in the previous 4 months are identified by a daily query of the electronic pharmacy database. A pharmacist reviews these patients' electronic health records to identify and exclude ineligible patients. Eligible patients are randomized evenly to the control or intervention arm and stratified by historical clinic nonadherence rates. Patients randomized to the intervention arm undergo a baseline assessment to clarify reasons for nonadherence and subsequently receive patient-tailored interventions based on their specific reasons. Interventions and follow-up are provided at the discretion of the intervening pharmacist. The primary outcome is PDC calculated at 8 months post-enrollment. Enrollment of 438 participants will provide 90% power to detect a 5% difference in PDC between the two arms within each nonadherence risk stratum. DISCUSSION: This trial will evaluate the effect of patient-tailored interventions on specialty medication adherence and will inform how often and why patients are misidentified as nonadherent. REGISTRATION: The trial was deemed a quality improvement initiative by the Vanderbilt University Institutional Review Board. It was registered in ClinicalTrials.gov (NCT03709277) on 17 October 2018.

Anatomic Site-Specific Complication Rates for Central Venous Catheter Insertions.

BACKGROUND: Central venous catheter (CVC) complication rates reflecting the application of modern insertion techniques to a clinically heterogeneous patient populations are needed to better understand procedural risk attributable to the 3 common anatomic insertion sites: internal jugular, subclavian, and femoral veins. We sought to define site-specific mechanical and duration-associated CVC complication rates across all hospital inpatients. METHODS: A retrospective chart review was conducted over 9 months at Georgetown University Hospital and Washington Hospital Center. Peripherally inserted central catheters and tunneled or fluoroscopically placed CVC's were excluded. Mechanical complications (retained guidewire, arterial injury, and pneumothorax) and duration-associated complications (deep vein thrombosis or pulmonary embolism, and central line-associated bloodstream infections) were identified. RESULTS: In all, 1179 CVC insertions in 801 adult patients were analyzed. Approximately 32% of patients had multiple lines placed. Of 1179 CVCs, 73 total complications were recorded, giving a total rate of one or more complications occurring per CVC of 5.9%. There was no statistically significant difference between site-specific complications. A total of 19 mechanical complications were documented, with a 1.5% complication rate of one or more mechanical complications occurring. A total of 54 delayed complications were documented, with a 4.4% complication rate of 1 or more delayed complications occurring. There were no statistically significant differences between anatomic sites for either total mechanical or total delayed complications. CONCLUSIONS: These results suggest that site-specific CVC complication rates may be less common than previously reported. These data further inform on the safety of modern CVC insertion techniques across all patient populations and clinical settings.

Ranking reactive glutamines in the fibrinogen αC region that are targeted by blood coagulant factor XIII.

Factor XIIIa (FXIIIa) introduces covalent γ-glutamyl-ε-lysyl crosslinks into the blood clot network. These crosslinks involve both the γ and α chains of fibrin. The C-terminal portion of the fibrin α chain extends into the αC region (210-610). Crosslinks within this region help generate a stiffer clot, which is more resistant to fibrinolysis. Fibrinogen αC (233-425) contains a binding site for FXIIIa and three glutamines Q237, Q328, and Q366 that each participate in physiological crosslinking reactions. Although these glutamines were previously identified, their reactivities toward FXIIIa have not been ranked. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry and nuclear magnetic resonance (NMR) methods were thus used to directly characterize these three glutamines and probe for sources of FXIIIa substrate specificity. Glycine ethyl ester (GEE) and ammonium chloride served as replacements for lysine. Mass spectrometry and 2D heteronuclear single quantum coherence NMR revealed that Q237 is rapidly crosslinked first by FXIIIa followed by Q366 and Q328. Both (15)NH4Cl and (15)N-GEE could be crosslinked to the three glutamines in αC (233-425) with a similar order of reactivity as observed with the MALDI-TOF mass spectrometry assay. NMR studies using the single αC mutants Q237N, Q328N, and Q366N demonstrated that no glutamine is dependent on another to react first in the series. Moreover, the remaining two glutamines of each mutant were both still reactive. Further characterization of Q237, Q328, and Q366 is important because they are located in a fibrinogen region susceptible to physiological truncations and mutation. The current results suggest that these glutamines play distinct roles in fibrin crosslinking and clot architecture.

Bandgap Tuning of Silicon Quantum Dots by Surface Functionalization with Conjugated Organic Groups.

The quantum confinement and enhanced optical properties of silicon quantum dots (SiQDs) make them attractive as an inexpensive and nontoxic material for a variety of applications such as light emitting technologies (lighting, displays, sensors) and photovoltaics. However, experimental demonstration of these properties and practical application into optoelectronic devices have been limited as SiQDs are generally passivated with covalently bound insulating alkyl chains that limit charge transport. In this work, we show that strategically designed triphenylamine-based surface ligands covalently bonded to the SiQD surface using conjugated vinyl connectivity results in a 70 nm red-shifted photoluminescence relative to their decyl-capped control counterparts. This suggests that electron density from the SiQD is delocalized into the surface ligands to effectively create a larger hybrid QD with possible macroscopic charge transport properties.

Single-step plasma synthesis of carbon-coated silicon nanoparticles.

We have developed a novel single-step technique based on nonthermal, radio frequency (rf) plasmas to synthesize sub-10 nm, core-shell, carbon-coated crystalline Si (c-Si) nanoparticles (NPs) for potential application in Li(+) batteries and as fluorescent markers. Hydrogen-terminated c-Si NPs nucleate and grow in a SiH4-containing, low-temperature plasma in the upstream section of a tubular quartz reactor. The c-Si NPs are then transported downstream by gas flow, and are coated with amorphous carbon (a-C) in a second C2H2-containing plasma. X-ray diffraction (XRD), X-ray photoelectron spectroscopy, and in situ attenuated total reflection Fourier transform infrared spectroscopy show that a thin, < 1 nm, 3C-SiC layer forms at the c-Si/a-C interface. By varying the downstream C2H2 plasma rf power, we can alter the nature of the a-C coating as well as the thickness of the interfacial 3C-SiC layer. The transmission electron microscopy (TEM) analysis is in agreement with the Si NP core size determined by Raman spectroscopy, photoluminescence spectroscopy, and XRD analysis. The size of the c-Si NP core, and the corresponding light emission from these NPs, was directly controlled by varying the thickness of the interfacial 3C-SiC layer. This size tunable emission thus also demonstrates the versatility of this technique for synthesizing c-Si NPs for potential applications in light emitting diodes, biological markers, and nanocrystal inks.

Climate change health assessment: a novel approach for Alaska Native communities.

OBJECTIVES: Develop a process for assessing climate change impacts on public health that identifies climate-health vulnerabilities and mechanisms and encourages adaptation. STUDY DESIGN: Multi-stakeholder, participatory, qualitative research. METHODS: A Climate Change Health Assessment (CCHA) was developed that involved 4 steps: (1) scoping to describe local conditions and engage stakeholders; (2) surveying to collect descriptive and quantitative data; (3) analysis to evaluate the data; and (4) planning to communicate findings and explore appropriate actions with community members. The health effects related to extreme weather, thinning ice, erosion, flooding, thawing permafrost and changing conditions of water and food resources were considered. RESULTS: The CCHA process was developed and performed in north-west Arctic villages. Refinement of the process took place in Point Hope, a coastal Inupiat village that practices whaling and a variety of other traditional subsistence harvest practices. Local observers identified climate change impacts that resulted in damaged health infrastructure, compromised food and water security and increased risk of injury. Priority health issues included thawing traditional ice cellars, diminished quality of the community water source and increased safety issues related to sea ice change. The CCHA increased awareness about health vulnerability and encouraged informed planning and decision-making. CONCLUSION: A community-scale assessment process guided by observation-based data can identify climate health impacts, raise awareness and encourage adaptive actions, thereby improving the response capacity of communities vulnerable to climate change.

Sequence of physical changes to the cell membrane during glucocorticoid-induced apoptosis in S49 lymphoma cells.

During apoptosis, physical changes in the plasma membrane prepare the cell for clearance by phagocytes and hydrolysis by secretory phospholipase A(2) (sPLA(2)). The relationships among these changes have not been adequately established, especially for hormone-stimulated apoptosis. This study addresses these issues for glucocorticoid-induced apoptosis in S49 lymphoma cells. Flow cytometry, microscopy, and fluorescence spectroscopy were used to assess merocyanine 540 emission, laurdan generalized polarization, phosphatidylserine exposure, caspase activation, and membrane permeability to propidium iodide in the absence and presence of sPLA(2). The earliest event observed was activation of cellular caspases. Results with membrane probes suggest that interlipid spacing also increases early during apoptosis and precedes transbilayer migration of phosphatidylserine, DNA fragmentation, and a general increase in lipid order associated with blebbing and dissolution of the cells. The activity of sPLA(2) appeared to be linked more to lipid spacing than to loss of membrane asymmetry. The early nature of some of these events and their ability to promote activity of a proinflammatory enzyme suggests the possibility of an inflammatory response during T-lymphocyte apoptosis.