Wesley H. Self

Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults

BACKGROUND Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among adults 18 years of age or older in five hospitals in Chicago and Nashville. Patients with recent hospitalization or severe immunosuppression were excluded. Blood, urine, and respiratory specimens were systematically collected for culture, serologic testing, antigen detection, and molecular diagnostic testing. Study radiologists independently reviewed chest radiographs. We calculated population-based incidence rates of community-acquired pneumonia requiring hospitalization according to age and pathogen. RESULTS From January 2010 through June 2012, we enrolled 2488 of 3634 eligible adults (68%). Among 2320 adults with radiographic evidence of pneumonia (93%), the median age of the patients was 57 years (interquartile range, 46 to 71); 498 patients (21%) required intensive care, and 52 (2%) died. Among 2259 patients who had radiographic evidence of pneumonia and specimens available for both bacterial and viral testing, a pathogen was detected in 853 (38%): one or more viruses in 530 (23%), bacteria in 247 (11%), bacterial and viral pathogens in 59 (3%), and a fungal or mycobacterial pathogen in 17 (1%). The most common pathogens were human rhinovirus (in 9% of patients), influenza virus (in 6%), and Streptococcus pneumoniae (in 5%). The annual incidence of pneumonia was 24.8 cases (95% confidence interval, 23.5 to 26.1) per 10,000 adults, with the highest rates among adults 65 to 79 years of age (63.0 cases per 10,000 adults) and those 80 years of age or older (164.3 cases per 10,000 adults). For each pathogen, the incidence increased with age. CONCLUSIONS The incidence of community-acquired pneumonia requiring hospitalization was highest among the oldest adults. Despite current diagnostic tests, no pathogen was detected in the majority of patients. Respiratory viruses were detected more frequently than bacteria. (Funded by the Influenza Division of the National Center for Immunizations and Respiratory Diseases.).

Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication

RATIONALE We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).

Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia

Abstract Background. The clinical significance of viruses detected in patients with community-acquired pneumonia (CAP) is often unclear. Methods. We conducted a prospective study to identify the prevalence of 13 viruses in the upper respiratory tract of patients with CAP and concurrently enrolled asymptomatic controls with real-time reverse-transcriptase polymerase chain reaction. We compared age-stratified prevalence of each virus between patients with CAP and controls and used multivariable logistic regression to calculate attributable fractions (AFs). Results. We enrolled 1024 patients with CAP and 759 controls. Detections of influenza, respiratory syncytial virus, and human metapneumovirus were substantially more common in patients with CAP of all ages than in controls (AFs near 1.0). Parainfluenza and coronaviruses were also more common among patients with CAP (AF, 0.5–0.75). Rhinovirus was associated with CAP among adults (AF, 0.93) but not children (AF, 0.02). Adenovirus was associated with CAP only among children <2 years old (AF, 0.77). Conclusions. The probability that a virus detected with real-time reverse-transcriptase polymerase chain reaction in patients with CAP contributed to symptomatic disease varied by age group and specific virus. Detections of influenza, respiratory syncytial virus, and human metapneumovirus among patients with CAP of all ages probably indicate an etiologic role, whereas detections of parainfluenza, coronaviruses, rhinovirus, and adenovirus, especially in children, require further scrutiny.

High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ED patients: implications for diagnosing pneumonia ☆

OBJECTIVE To evaluate the diagnostic performance of chest x-ray (CXR) compared to computed tomography (CT) for detection of pulmonary opacities in adult emergency department (ED) patients. METHODS We conducted an observational cross-sectional study of adult patients presenting to 12 EDs in the United States from July 1, 2003, through November 30, 2006, who underwent both CXR and chest CT for routine clinical care. CXRs and CT scans performed on the same patient were matched. CXRs and CT scans were interpreted by attending radiologists and classified as containing pulmonary opacities if the final radiologist report noted opacity, infiltrate, consolidation, pneumonia, or bronchopneumonia. Using CT as a criterion standard, the diagnostic test characteristics of CXR to detect pulmonary opacities were calculated. RESULTS The study cohort included 3423 patients. Shortness of breath, chest pain and cough were the most common complaints, with 96.1% of subjects reporting at least one of these symptoms. Pulmonary opacities were visualized on 309 (9.0%) CXRs and 191 (5.6 %) CT scans. CXR test characteristics for detection of pulmonary opacities included: sensitivity 43.5% (95% CI, 36.4%-50.8%); specificity 93.0% (95% CI, 92.1%-93.9%); positive predictive value 26.9% (95% CI, 22.1%-32.2%); and negative predictive value 96.5% (95% CI, 95.8%-97.1%). CONCLUSION In this multicenter cohort of adult ED patients with acute cardiopulmonary symptoms, CXR demonstrated poor sensitivity and positive predictive value for detecting pulmonary opacities. Reliance on CXR to identify pneumonia may lead to significant rates of misdiagnosis.

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown. Objectives: To pilot a cluster‐randomized, multiple‐crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids. Methods: This was a cluster‐randomized, multiple‐crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringers solution or Plasma‐Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction. Measurements and Main Results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500‐3,377] vs. 1,617 ml [500‐3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98). Conclusions: An electronic health record‐embedded, cluster‐randomized, multiple‐crossover trial comparing saline with balanced crystalloids can produce well‐balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination

IMPORTANCE Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection. OBJECTIVE To assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia. DESIGN, SETTING, AND PARTICIPANTS The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 at 4 US sites. In this case-control study, we used EPIC data from patients 6 months or older with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (case) and influenza-negative (control) patients with pneumonia, controlling for demographics, comorbidities, season, study site, and timing of disease onset. Vaccine effectiveness was estimated as (1 - adjusted odds ratio) × 100%. EXPOSURE Influenza vaccination, verified through record review. MAIN OUTCOMES AND MEASURES Influenza pneumonia, confirmed by real-time reverse-transcription polymerase chain reaction performed on nasal/oropharyngeal swabs. RESULTS Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%) with influenza-associated pneumonia and 766 of 2605 controls (29%) with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI, 0.28-0.68; estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%). CONCLUSIONS AND RELEVANCE Among children and adults hospitalized with community-acquired pneumonia, those with laboratory-confirmed influenza-associated pneumonia, compared with those with pneumonia not associated with influenza, had lower odds of having received influenza vaccination.

Balanced Crystalloids versus Saline in Critically Ill Adults

BACKGROUND Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS We conducted a single‐center, pragmatic, multiple‐crossover trial comparing balanced crystalloids (lactated Ringers solution or Plasma‐Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16‐month trial. The primary outcome was hospital‐free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days — a composite of death from any cause, new renal‐replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital‐free days did not differ between the balanced‐crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01). CONCLUSIONS Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital‐free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT‐ED ClinicalTrials.gov number, NCT02614040.)

Reducing Blood Culture Contamination in the Emergency Department: An Interrupted Time Series Quality Improvement Study

OBJECTIVES Blood culture contamination is a common problem in the emergency department (ED) that leads to unnecessary patient morbidity and health care costs. The study objective was to develop and evaluate the effectiveness of a quality improvement (QI) intervention for reducing blood culture contamination in an ED. METHODS The authors developed a QI intervention to reduce blood culture contamination in the ED and then evaluated its effectiveness in a prospective interrupted times series study. The QI intervention involved changing the technique of blood culture specimen collection from the traditional clean procedure to a new sterile procedure, with standardized use of sterile gloves and a new materials kit containing a 2% chlorhexidine skin antisepsis device, a sterile fenestrated drape, a sterile needle, and a procedural checklist. The intervention was implemented in a university-affiliated ED and its effect on blood culture contamination evaluated by comparing the biweekly percentages of blood cultures contaminated during a 48-week baseline period (clean technique) and 48-week intervention period (sterile technique), using segmented regression analysis with adjustment for secular trends and first-order autocorrelation. The goal was to achieve and maintain a contamination rate below 3%. RESULTS During the baseline period, 321 of 7,389 (4.3%) cultures were contaminated, compared to 111 of 6,590 (1.7%) during the intervention period (p < 0.001). In the segmented regression model, the intervention was associated with an immediate 2.9% (95% confidence interval [CI] = 2.2% to 3.2%) absolute reduction in contamination. The contamination rate was maintained below 3% during each biweekly interval throughout the intervention period. CONCLUSIONS A QI assessment of ED blood culture contamination led to development of a targeted intervention to convert the process of blood culture collection from a clean to a fully sterile procedure. Implementation of this intervention led to an immediate and sustained reduction of contamination in an ED with a high baseline contamination rate.

Reducing the Blood Culture Contamination Rate in a Pediatric Emergency Department and Subsequent Cost Savings

BACKGROUND AND OBJECTIVE: Blood culture contamination in the pediatric population remains a significant quality and safety issue because false-positive blood cultures lead to unnecessary use of resources and testing. In addition, few studies describe interventions to reduce peripheral blood culture contamination rates in this population. We hypothesized that the introduction of a standardized sterile collection process would reduce the pediatric emergency department’s peripheral blood culture contamination rate and unnecessary use of resources. METHODS: A sterile blood culture collection process was designed by analyzing current practice and identifying areas in which sterile technique could be introduced. To spread the new technique, a web-based educational model was developed and disseminated. Subsequently, all nursing staff members were expected to perform peripheral blood cultures by using the modified sterile technique. RESULTS: The peripheral blood culture contamination rate was reduced from 3.9% during the baseline period to 1.6% during the intervention period (P < .0001), with yearly estimated savings of ∼

Low Numeracy Is Associated With Increased Odds of 30-Day Emergency Department or Hospital Recidivism for Patients With Acute Heart Failure

250 000 in hospital charges. CONCLUSIONS: Subsequent to our intervention, there was a significant reduction of the peripheral blood culture contamination rate as well as considerable cost savings to the institution. When performed in a standardized fashion by using sterile technique, blood culture collection with low contamination rates can be performed via the insertion of an intravenous catheter.