Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infection.

BACKGROUND: Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. METHODS: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. RESULTS: A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%). CONCLUSIONS: This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715.

Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality.

BACKGROUND: Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. METHODS: This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. RESULTS: During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. CONCLUSIONS: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

The Effects of Kentucky's Comprehensive Opioid Legislation on Patients Presenting with Prescription Opioid or Heroin Abuse to One Urban Emergency Department.

BACKGROUND: Prescription opioid abuse has increased to epidemic proportions in the United States. Kentucky, along with other states, passed comprehensive legislation to monitor and curb opioid prescribing. OBJECTIVES: This paper characterizes patients who presented to the emergency department (ED) after abusing prescription opioids and heroin prior to and after the passage of House Bill 1 (HB1) in April 2012. METHODS: Based on a retrospective review of ED visits from 2009-2014 in one urban adult facility, patients were included if the chief complaint or diagnosis was directly related to prescription opioid or heroin abuse. The primary outcome is the number and type of substance abused by each ED patient. RESULTS: From 2009-2014, 2945 patients presented to the ED after prescription opioid or heroin abuse. The number of prescription opioid patients decreased from 215 (of 276 patients) in 2009 to 203 (of 697 patients) in 2014; 77.9% of patients abused opioids in 2009, vs. 29% in 2014 (a 63% decrease). The number of heroin patients increased from 61 in 2009 to 494 in 2014; 22% of patients in 2009 abused heroin, vs. 71% in 2014 (a 221% increase). Both piecewise regression and autoregressive integrated moving average trend models showed an increased trend in patient heroin abuse beginning in 2011-2012. CONCLUSIONS: Our facility experienced a decrease in the number of patients who abused prescription opioids and an increase in the number of patients who abused heroin over the study period. The transition seemed to occur just prior to, or concurrent with, enforcement of statewide opioid legislation.

Community-Acquired Pneumonia in the Immunocompromised Host: Epidemiology and Outcomes.

Background: The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods: This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results: A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions: Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.

Socioeconomic Position and the Incidence, Severity, and Clinical Outcomes of Hospitalized Patients With Community-Acquired Pneumonia.

OBJECTIVES: The influence of socioeconomic disparities on adults with pneumonia is not well understood. The objective of our study was to evaluate the relationship between community-level socioeconomic position, as measured by an area deprivation index, and the incidence, severity, and outcomes among adults with community-acquired pneumonia (CAP). METHODS: This was an ancillary study of a population-based, prospective cohort study of patients hospitalized with CAP in Louisville, Kentucky, from June 1, 2013, through May 31, 2015. We used a race-specific, block group-level area deprivation index as a proxy for community-level socioeconomic position and evaluated it as a predictor of CAP incidence, CAP severity, early clinical improvement, 30-day mortality, and 1-year mortality. RESULTS: The cohort comprised 6349 unique adults hospitalized with CAP. CAP incidence per 100 000 population increased significantly with increasing levels of area deprivation, from 303 in tertile 1 (low deprivation), to 467 in tertile 2 (medium deprivation), and 553 in tertile 3 (high deprivation) (P < .001). Adults in medium- and high-deprivation areas had significantly higher odds of severe CAP (tertile 2 odds ratio [OR] = 1.2 [95% confidence interval (CI), 1.06-1.39]; tertile 3 OR = 1.4 [95% CI, 1.18-1.64] and 1-year mortality (tertile 2 OR = 1.3 [95% CI, 1.11-1.54], tertile 3 OR = 1.3 [95% CI, 1.10-1.64]) than adults in low-deprivation areas. CONCLUSIONS: Compared with adults residing in low-deprivation areas, adults residing in high-deprivation areas had an increased incidence of CAP, and they were more likely to have severe CAP. Beyond 30 days of care, we identified an increased long-term mortality for persons in high-deprivation areas. Community-level socioeconomic position should be considered an important factor for research in CAP and policy decisions.

Discovery and predictive modeling of urine microbiome, metabolite and cytokine biomarkers in hospitalized patients with community acquired pneumonia.

Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (Streptococcus pneumoniae and Staphylococcus aureus) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a + 90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.

Googling your hand hygiene data: Using Google Forms, Google Sheets, and R to collect and automate analysis of hand hygiene compliance monitoring.

BACKGROUND: Hand hygiene is one of the most important interventions in the quest to eliminate healthcare-associated infections, and rates in healthcare facilities are markedly low. Since hand hygiene observation and feedback are critical to improve adherence, we created an easy-to-use, platform-independent hand hygiene data collection process and an automated, on-demand reporting engine. METHODS: A 3-step approach was used for this project: 1) creation of a data collection form using Google Forms, 2) transfer of data from the form to a spreadsheet using Google Spreadsheets, and 3) creation of an automated, cloud-based analytics platform for report generation using R and RStudio Shiny software. RESULTS: A video tutorial of all steps in the creation and use of this free tool can be found on our YouTube channel: https://www.youtube.com/watch?v=uFatMR1rXqU&t. The on-demand reporting tool can be accessed at: https://crsp.louisville.edu/shiny/handhygiene. CONCLUSIONS: This data collection and automated analytics engine provides an easy-to-use environment for evaluating hand hygiene data; it also provides rapid feedback to healthcare workers. By reducing some of the data management workload required of the infection preventionist, more focused interventions may be instituted to increase global hand hygiene rates and reduce infection.

Methods for computational disease surveillance in infection prevention and control: Statistical process control versus Twitter's anomaly and breakout detection algorithms.

BACKGROUND: Although not all health care-associated infections (HAIs) are preventable, reducing HAIs through targeted intervention is key to a successful infection prevention program. To identify areas in need of targeted intervention, robust statistical methods must be used when analyzing surveillance data. The objective of this study was to compare and contrast statistical process control (SPC) charts with Twitter's anomaly and breakout detection algorithms. METHODS: SPC and anomaly/breakout detection (ABD) charts were created for vancomycin-resistant Enterococcus, Acinetobacter baumannii, catheter-associated urinary tract infection, and central line-associated bloodstream infection data. RESULTS: Both SPC and ABD charts detected similar data points as anomalous/out of control on most charts. The vancomycin-resistant Enterococcus ABD chart detected an extra anomalous point that appeared to be higher than the same time period in prior years. Using a small subset of the central line-associated bloodstream infection data, the ABD chart was able to detect anomalies where the SPC chart was not. DISCUSSION: SPC charts and ABD charts both performed well, although ABD charts appeared to work better in the context of seasonal variation and autocorrelation. CONCLUSIONS: Because they account for common statistical issues in HAI data, ABD charts may be useful for practitioners for analysis of HAI surveillance data.

Antibiotic Timing and Outcomes in Sepsis.

BACKGROUND: We evaluated the effect of time spent in the emergency department (ED) and process of care on mortality and length of hospital stay in patients with sepsis or septic shock. METHODS: An observational cohort study was conducted on 117 patients who came through the University of Louisville Hospital ED and subsequently were directly admitted to the intensive care unit (ICU). Variables of interest were time in the ED from triage to physical transport to the ICU, from triage to antibiotic(s) ordered, and from triage to antibiotic(s) administered. Expected mortality was calculated according to the University Health System Consortium Database. Primary and secondary outcomes were in-hospital death and hospital length of stay in days, respectively. RESULTS: We found no significant association between time in the ED and mortality between survivors and nonsurvivors (5.5 versus 5.7 hours, P = 0.804). After adjusting for expected mortality, a 22% increase in mortality risk was found for each hour delay from triage to antibiotic(s) ordered; a 15% increase in mortality risk was observed for each hour from triage to antibiotic(s) given. Both time from triage to antibiotic(s) ordered (hazard ratio [HR] = 0.8, P = 0.044) and time from triage to antibiotic(s) delivery (HR = 0.79, P = 0.0092) were independently associated with an increased hospital stay (HR = 0.79, P = 0.0092). CONCLUSION: Though no significant association between mortality and ED time was demonstrated, we observed a significant increase in mortality in septic patients with both delays in antibiotic(s) order and administration. Delay in care also resulted in increased hospital stays both overall and in the ICU.

Enteral nutrition as stress ulcer prophylaxis in critically ill patients: A randomized controlled exploratory study.

PURPOSE: We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress-related gastrointestinal (GI) bleeding in mechanically ventilated patients. MATERIALS AND METHODS: Prospective, double blind, randomized, placebo-controlled, exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals. Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress-ulcer prophylaxis. The incidences of clinically significant and overt GI bleeding were compared in the two groups. RESULTS: 124 patients were enrolled in the study. After exclusion of 22 patients, 102 patients were included in analysis: 55 patients in the treatment group and 47 patients in the placebo group. Two patients (one from each group) showed signs of overt GI bleeding (overall incidence 1.96%), and both patients experienced a drop of >3 points in hematocrit in a 24-hour period indicating a clinically significant GI bleed. There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups (p=0.99). CONCLUSION: We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients. The routine prescription of acid-suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation.

Process control charts in infection prevention: Make it simple to make it happen.

BACKGROUND: Quality improvement is central to Infection Prevention and Control (IPC) programs. Challenges may occur when applying quality improvement methodologies like process control charts, often due to the limited exposure of typical IPs. Because of this, our team created an open-source database with a process control chart generator for IPC programs. The objectives of this report are to outline the development of the application and demonstrate application using simulated data. METHODS: We used Research Electronic Data Capture (REDCap Consortium, Vanderbilt University, Nashville, TN), R (R Foundation for Statistical Computing, Vienna, Austria), and R Studio Shiny (R Foundation for Statistical Computing) to create an open source data collection system with automated process control chart generation. We used simulated data to test and visualize both in-control and out-of-control processes for commonly used metrics in IPC programs. RESULTS: The R code for implementing the control charts and Shiny application can be found on our Web site (https://github.com/ul-research-support/spcapp). Screen captures of the workflow and simulated data indicating both common cause and special cause variation are provided. CONCLUSIONS: Process control charts can be easily developed based on individual facility needs using freely available software. Through providing our work free to all interested parties, we hope that others will be able to harness the power and ease of use of the application for improving the quality of care and patient safety in their facilities.

Using cluster analysis of cytokines to identify patterns of inflammation in hospitalized patients with community-acquired pneumonia: a pilot study.

INTRODUCTION: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. METHODS: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. RESULTS: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. CONCLUSIONS: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

Disinfectant sprays versus wipes: Applications in behavioral health.

We evaluated the utility and usability of a spray and a wipe-based cleaner/disinfectant in a behavioral health setting where health care providers institute cleaning and disinfection procedures. The spray-based version resulted in significantly lower adenosine triphosphate readings after use compared with the wipe version. Staff surveys indicated that users preferred the spray version.