Risk factors and outcomes for ineffective empiric treatment of sepsis caused by gram-negative pathogens: Stratification by onset of infection

ABSTRACT Sepsis and septic shock remain serious consequences of infections, with reported mortality rates in excess of 40 percent. Timely antibiotic therapy in cases of sepsis and septic shock is recognized as an important determinant of outcome. However, the administration of ineffective empirical treatment (IET) (an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results) is associated with excess mortality compared to effective empirical treatment (EET). We examined all hospitalized patients at Barnes-Jewish Hospital with a sterile site (blood or pleural, abdominal, cerebrospinal, synovial, and pericardial fluid) culture positive for Gram-negative (GN) bacteria combined with a primary or secondary ICD-9-CM code for severe sepsis (995.92) or septic shock (785.52) between January 2010 and October 2015. Variables significantly associated with early-onset (&lt;48 h of hospitalization) IET of GN sterile site sepsis and septic shock included age, recent hospitalization, and prior intravenous antibiotics. Late-onset IET was associated with increasing numbers of hospitalization days before infection onset and prior intravenous antibiotic administration. For patients with early-onset infection, we found no difference in rates of survival between patients receiving IET and EET. However, patients in the late-onset infection group receiving IET had a statistically lower rate of survival than those receiving EET. These data suggest that risk factors and outcomes for IET can vary based on the time of onset of infection. Our results also highlight the importance of prior intravenous antibiotic exposure as a risk factor for IET in infections by GN bacteria regardless of the time of onset of infection. </jats:p

Importance of site of infection and antibiotic selection in the treatment of carbapenem-resistant Pseudomonas aeruginosa sepsis

ABSTRACT In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas aeruginosa sepsis, we observed a significantly higher risk of mortality associated with respiratory tract infection (risk ratio [RR], 1.20; 95% confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside monotherapy was associated with increased mortality, even after adjusting for confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent across multiple sites of infection. </jats:p

An Electrochemical Cell for the Efficient Turn Around of Wafer Working Electrodes

We present a new design for an electrochemical cell for use with wafer working electrodes. The key feature of the design is the use of half turn thumb screws to form a liquid-tight seal between an o-ring and the sample surface. The assembly or disassembly of the cell requires a half turn of each thumb screw, which facilitates the quick turn around of wafer samples. The electrochemical performance of the cell is demonstrated by cyclic voltammetry and double step chronoamperometry measurements of the ferricyanide/ferrocyanide couple

Clinical implications for patients treated inappropriately for community-acquired pneumonia in the emergency department

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most common infections presenting to the emergency department (ED). Increasingly, antibiotic resistant bacteria have been identified as causative pathogens in patients treated for CAP, especially in patients with healthcare exposure risk factors. METHODS: We retrospectively identified adult subjects treated for CAP in the ED requiring hospital admission (January 2003-December 2011). Inappropriate antibiotic treatment, defined as an antibiotic regimen that lacked in vitro activity against the isolated pathogen, served as the primary end point. Information regarding demographics, severity of illness, comorbidities, and antibiotic treatment was recorded. Logistic regression was used to determine factors independently associated with inappropriate treatment. RESULTS: The initial cohort included 259 patients, 72 (27.8%) receiving inappropriate antibiotic treatment. There was no difference in hospital mortality between patients receiving inappropriate and appropriate treatment (8.3% vs. 7.0%; p = 0.702). Hospital length of stay (10.3 ± 12.0 days vs. 7.0 ± 8.9 days; p = 0.017) and 30-day readmission (23.6% vs. 12.3%; p = 0.024) were greater among patients receiving inappropriate treatment. Three variables were independently associated with inappropriate treatment: admission from long-term care (AOR, 9.05; 95% CI, 3.93-20.84), antibiotic exposure in the previous 30 days (AOR, 1.85; 95% CI, 1.35-2.52), and chronic obstructive pulmonary disease (AOR, 2.05; 95% CI, 1.52-2.78). CONCLUSION: Inappropriate antibiotic treatment of presumed CAP in the ED negatively impacts patient outcome and readmission rate. Knowledge of risk factors associated with inappropriate antibiotic treatment of presumed CAP could advance the management of patients with pneumonia presenting to the ED and potentially improve patient outcomes

Fluid balance and cardiac function in septic shock as predictors of hospital mortality

INTRODUCTION: Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical. METHODS: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled. RESULTS: A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome. CONCLUSIONS: Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed

Themelia: the irreducible microstructure of black holes

We argue that the fundamental "atomic objects" in string theory are themelia: extended objects that have 16 supersymmetries locally. We show that all existing smooth horizonless microstate geometries can be seen as bound states of themelia, and we conjecture that all such bound states with suitable KKM charges will give rise to microstate geometries. We also construct the most general themelion with a three-torus isometry and show that it interpolates between superstrata and the super-maze.Comment: 6 page

AD|ARC (Administrative Data| Agricultural Research Collection): Linking individual, household and farm business data for agricultural research – The challenges and opportunities of partnership working across ADR UK

Objectives ADARC is a partnership of six government departments and three research institutions across ADR-UK aiming to build four Research Ready Datasets about farming households. A|ARC requires government data linking experts to work closely with agricultural statisticians and academics across traditional boundaries pooling a wide range of data and expertise. Methods The ADARC partnership aims to build a model of collaborative working for administrative data research. ADARC brings together those collecting data with those linking and analysing de-identified data and eventually those using results to develop future policies. The data is from several different sources at individual, household and business levels requiring new methodologies developed by this collaboration. ADARC is also working between all four ADR centres to share learning across the ADR network building relationships for future projects beyond agriculture. The linkage process has been different in all four nations but this has offered new learning for all involved. Results Due to the Covid-19 pandemic, Phase 1 of the project has been slower than hoped. However, ADARC has shown that it is possible to conduct a truly UK-wide four nation project. Data linking is underway in all four nations bringing together data on individuals, households and businesses and analysis has begun in Wales and England. The project to date has faced the usual challenges of data acquisition and data quality issues which the partnership approach has been vital for overcoming. Despite this, we’ve demonstrated that there’s a huge level of enthusiasm for working together across organisational barriers. ADARC has just been funded for Phase 2 to expand the datasets in scope and explore the feasibility of linking in spatial data. Conclusion ADARC has created a model which demonstrates that partnership working is essential for fully achieving the objective of ADR UK of unlocking the potential of administrative data. The lessons of ADARC also provides a powerful case study for future cross-UK projects far beyond agriculture

Assessment of antibiotic de-escalation by spectrum score in patients with nosocomial pneumonia: A single-center, retrospective cohort study

Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure. Methods: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with no de-escalation (NDE). The primary outcome was composite treatment failure, defined as all-cause mortality or readmission for pneumonia within 30 days of diagnosis. Results: Of 11860 admissions screened, 1812 unique patient-admissions were included (1102 HAP, 710 VAP). Fewer patients received DE (876 DE vs 1026 NDE). Groups were well matched at baseline, although more patients receiving DE had respiratory cultures ordered (56.6% vs 50.6%, Conclusions: De-escalation and NDE resulted in similar rates of 30-day treatment failure; however, DE was associated with fewer antibiotic days, episodes o

Analysis of Electrodeposited Nickel-Iron Alloy Film Composition Using Particle-Induced X-Ray Emission

The elemental composition of electrodeposited NiFe thin films was analyzed with particle-induced X-ray emission (PIXE). The thin films were electrodeposited on polycrystalline Au substrates from a 100mM NiSO4, 10 mM FeSO4, 0.5M H3BO3, and 1M Na2SO4 solution. PIXE spectra of these films were analyzed to obtain relative amounts of Ni and Fe as a function of deposition potential and deposition time. The results show that PIXE can measure the total deposited metal in a sample over at least four orders of magnitude with similar fractional uncertainties. The technique is also sensitive enough to observe the variations in alloy composition due to sample nonuniformity or variations in deposition parameters

Personality correlates of dispositional forgiveness: a direct comparison of interpersonal and self-forgiveness using common transgression scenarios

Although the personality correlates of dispositional interpersonal forgiveness (forgiveness of others) have been well characterized, those of dispositional self-forgiveness are less well understood. Moreover, when the personality correlates are examined for both types of forgiveness, the comparison has been based on participants’ self-report ratings on questionnaires. The current study sought to address these gaps in the literature by adopting a scenario-based approach, which has been used less frequently, especially in self-forgiveness research. A total of 160 participants read six fictional scenarios, each describing a severe transgression, from the perspective of the transgressor (self-forgiveness, n = 78) or the victim (interpersonal forgiveness, n = 82) of the transgression, and then responded to several items assessing different facets of forgiveness (avoidance, revenge, and benevolence). Participants’ personality (Big Five) and explanatory style were also assessed. Consistent with prior literature, agreeableness and neuroticism generally predicted different facets of interpersonal forgiveness. These two personality traits also predicted facets of self-forgiveness, but, additionally, conscientiousness and one’s tendency to internalize failure (the personal component of explanatory style) uniquely predicted self-forgiveness, especially avoidance motivations. These results point to both similarities and differences in the personality correlates of interpersonal and self-forgiveness. As a secondary, more exploratory aim, the current study compared the results from our scenario-based assessment of forgiveness to those based on a commonly used questionnaire, the Other and Self subscales of the Heartland Forgiveness Scale (HFS). As expected, the Other subscale of the HFS were associated with levels of interpersonal forgiveness assessed with our transgression scenarios, but, surprisingly, the HFS Self subscale was more strongly related to interpersonal than self-forgivess assessed with scenarios. Moreover, the Self subscale was not associated with levels of self-forgiveness assessed with transgression scenarios, except for avoidance motivations. These results suggest that scenario-based and questionnaire-based methods may capture different facts of forgiveness and cannot be used interchangeably, especially for the assessment of self-forgiveness. More generally, the current study illustrates the importance of conducting direct within-study comparisons of interpersonal and self-forgiveness as well as of different assessment methods to better understand the similarities and differences between the two types of forgiveness