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BackgroundThe relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from coronavirus disease 2019 (COVID-19) remains incompletely understood. Emerging evidence suggests that metabolic risk factors may also vary by age. This study aimed to determine the association between common patient characteristics and mortality across age-groups among COVID-19 inpatients.MethodsWe performed a retrospective cohort study of patients discharged from hospitals in the Premier Healthcare Database between April–June 2020. Inpatients were identified using COVID-19 ICD-10-CM diagnosis codes. A priori-defined exposures were sex and present-on-admission hypertension, diabetes, obesity, and interactions between age and these comorbidities. Controlling for additional confounders, we evaluated relationships between these variables and in-hospital mortality in a log-binomial model.ResultsAmong 66 646 (6.5%) admissions with a COVID-19 diagnosis, across 613 U.S. hospitals, 12 388 (18.6%) died in-hospital. In multivariable analysis, male sex was independently associated with 30% higher mortality risk (aRR, 1.30, 95% CI: 1.26–1.34). Diabetes without chronic complications was not a risk factor at any age (aRR 1.01, 95% CI: 0.96–1.06), and hypertension without chronic complications was a risk factor only in 20–39 year-olds (aRR, 1.68, 95% CI: 1.17–2.40). Diabetes with chronic complications, hypertension with chronic complications, and obesity were risk factors in most age-groups, with highest relative risks among 20–39 year-olds (respective aRRs 1.79, 2.33, 1.92; P-values ≤ .002).ConclusionsHospitalized men with COVID-19 are at increased risk of death across all ages. Hypertension, diabetes with chronic complications, and obesity demonstrated age-dependent effects, with the highest relative risks among adults aged 20–39.

BACKGROUND: Sepsis is the leading cause of in-hospital death. The SEP-1 sepsis bundle is a protocol for early sepsis care that requires providers to diagnose and treat sepsis quickly. Limited evidence suggests that adherence to the sepsis bundle is lower in cases of hospital-onset sepsis. OBJECTIVE: To compare sepsis bundle adherence in hospital-onset vs. community-onset sepsis. DESIGN: Retrospective cohort study using multivariable analysis of clinical data. PARTICIPANTS: A total of 4658 inpatients age 18 or older were identified by diagnosis codes consistent with sepsis or disseminated infection. SETTING: Four university hospitals in California between 2014 and 2016. MAIN OUTCOMES AND MEASURES: The primary outcome was adherence to key components of the sepsis bundle defined by the Centers for Medicare and Medicaid Services in their core measure, SEP-1. Covariates included clinical characteristics related to the patient, infection, and pathogen. KEY RESULTS: Compared with community-onset, cases of hospital-onset sepsis were less likely to receive SEP-1 adherent care (relative risk 0.33, 95% confidence interval 0.29–0.38, p

Hospitalized patients with SARS-CoV-2 infection (COVID-19) often receive antibiotics for suspected bacterial coinfection. We estimated the incidence of bacterial coinfection and secondary infection in COVID-19 using clinical diagnoses to determine how frequently antibiotics are administered when bacterial infection is absent. We performed a retrospective cohort study of inpatients with COVID-19 present on admission to hospitals in the Premier Healthcare Database between April and June 2020. Bacterial infections were defined using ICD-10-CM diagnosis codes and associated “present on admission” coding. Coinfections were defined by bacterial infection present on admission, while secondary infections were defined by bacterial infection that developed after admission. Coinfection and secondary infection were not mutually exclusive. A total of 18.5% of 64,961 COVID-19 patients (n = 12,040) presented with bacterial infection at admission, 3.8% (n = 2,506) developed secondary infection after admission, and 0.9% (n = 574) had both; 76.3% (n = 49,551) received an antibiotic while hospitalized, including 71% of patients who had no diagnosis of bacterial infection. Secondary bacterial infection occurred in 5.7% of patients receiving steroids in the first 2 days of hospitalization, 9.9% receiving tocilizumab in the first 2 days of hospitalization, and 10.3% of patients receiving both. After adjusting for patient and hospital characteristics, bacterial coinfection (adjusted relative risk [aRR], 1.15; 95% confidence interval [CI], 1.11 to 1.20) and secondary infection (aRR 1.93; 95% CI, 1.82 to 2.04) were both independently associated with increased mortality. Although 1 in 5 inpatients with COVID-19 presents with bacterial infection, secondary infections in the hospital are uncommon. Most inpatients with COVID-19 receive antibiotic therapy, including 71% of those not diagnosed with bacterial infection.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China in December 2019 and is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19). Approximately one-third of the patients with COVID-19 require intensive care unit (ICU) admission, and almost 30% of the patients develop acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is used as salvage therapy for severe ARDS. The role of ECMO in the treatment of COVID-19 remains unclear, although there is emerging evidence that this approach may be an effective salvage therapy for severe ARDS. Case Presentation: We present a case of a previously healthy 39-year-old Hispanic male who presented to the hospital with flu-like symptoms, including headache, fatigue, and myalgia for 8 days in late April 2020. He denied dyspnea on exertion. The patient’s symptoms progressed, resulting in pneumonia and acute respiratory distress syndrome (ARDS). The patient was managed with prone positioning, convalescent plasma and veno-venous extracorporeal membrane oxygenation (VV-ECMO) for 35 days. The patient successfully recovered and was able to ambulate independently and was discharged home from an acute care hospital without oxygen supplementation on hospital day 63. Conclusion: We present one of the first few documented cases of ECMO for severe ARDS due to COVID-19. After a prolonged hospital course requiring VV-ECMO, the patient was discharged home from an acute care hospital without oxygen requirement and ambulated independently, likely as a result of daily aggressive mobility-focused rehabilitation.

Objective:In the absence of pyuria, positive urine cultures are unlikely to represent infection. Conditional urine reflex culture policies have the potential to limit unnecessary urine culturing. We evaluated the impact of this diagnostic stewardship intervention.Design:We conducted a retrospective, quasi-experimental (nonrandomized) study, with interrupted time series, from August 2013 to January 2018 to examine rates of urine cultures before versus after the policy intervention. We compared 3 intervention sites to 3 control sites in an aggregated series using segmented negative binomial regression.Setting:The study included 6 acute-care hospitals within the Veterans’ Health Administration across the United States.Participants:Adult patients with at least 1 urinalysis ordered during acute-care admission, excluding pregnant patients or those undergoing urological procedures, were included.Methods:At the intervention sites, urine cultures were performed if a preceding urinalysis met prespecified criteria. No such restrictions occurred at the control sites. The primary outcome was the rate of urine cultures performed per 1,000 patient days. The safety outcome was the rate of gram-negative bloodstream infection per 1,000 patient days.Results:The study included 224,573 urine cultures from 50,901 admissions in 24,759 unique patients. Among the intervention sites, the overall average number of urine cultures performed did not significantly decrease relative to the preintervention period (5.9% decrease; P = 0.8) but did decrease by 21% relative to control sites (P < .01). We detected no significant difference in the rates of gram-negative bloodstream infection among intervention or control sites (P = .49).Conclusions:Conditional urine reflex culture policies were associated with a decrease in urine culturing without a change in the incidence of gram-negative bloodstream infection.

Objectives: Evidence supporting collection of follow-up blood cultures for Gram-negative bacteremia is mixed. We sought to understand why providers order follow-up blood cultures when managing P. aeruginosa bacteremia and whether follow-up blood cultures in this context are associated with short- and long-term survival. Methods: We conducted a retrospective cohort study of adult inpatients with P. aeruginosa bacteremia at the University of Maryland Medical Center in 2015–2020. Kaplan-Meier survival curves and Cox regression with time-varying covariates were used to evaluate the association between follow-up blood cultures and time to mortality within 30 days of first positive blood culture. Provider justifications for follow-up blood cultures were identified through chart review. Results: Of 159 eligible patients, 127 (80%) had follow-up blood cultures, including 9 (7%) that were positive for P. aeruginosa and 10 (8%) that were positive for other organisms. Follow-up blood cultures were typically collected “to ensure clearance” or “to guide antibiotic therapy.” Overall, 30-day mortality was 25.2%. After risk adjustment for patient characteristics, follow-up blood cultures were associated with a nonsignificant reduction in mortality risk (hazard ratio, 0.43; 95% confidence interval, 1.08; P = .071). In exploratory analyses, the potential mortality reduction from follow-up blood cultures was driven by their use in patients with Pitt bacteremia scores >0. Conclusions: Follow-up blood cultures are commonly collected for P. aeruginosa bacteremia but infrequently identify persistent bacteremia. Targeted use of follow-up blood cultures based on severity of illness may reduce unnecessary culturing.

Syndromic gastrointestinal (GI) panels are molecular tests that evaluate stool specimens for multiple enteric pathogens simultaneously, including viruses, bacteria, and parasites. The Luminex xTAG GI panel includes 14 microbial targets and the Biofire FilmArray GI panel includes 22. The purpose of this scoping review was to describe clinical use of these two commercially available syndromic GI panels. Compared with conventional testing, syndromic panels increase the number of potential pathogens identified by two- to fivefold. Syndromic panels were associated with non-reproducible results, positive results in the absence of clinical disease, and positive results for pathogens of unclear clinical significance. Syndromic panels were less likely to provide new information when performed > 72 h after hospital admission or when repeated within 4 weeks of a previous test. Process measures or clinical outcomes related to testing were infrequently reported. Outcomes-based research is needed to determine the clinical impact of syndromic GI panels. Strategies for diagnostic stewardship that may increase the utility of GI panels include (1) development of clinical criteria for testing, (2) use of multi-step testing algorithms that start with tests for the most common organisms (Clostridium difficile and norovirus), (3) selective reporting of results, (4) reporting results through a mediator such as the infection preventionist or antibiotic stewardship pharmacist, and (5) maintenance of separate pathways for C. difficile testing.

Nationally-representative data suggest an association between lack of insurance and in-hospital death from sepsis (Kumar et al., 2014). It remains to be determined whether this association is attributable to differences in baseline health, care-seeking behaviors, hospital care, or other factors. Purpose To determine whether organ dysfunction present on admission for community-onset sepsis mediates the association between lack of insurance and mortality in sepsis. Materials and methods Retrospective cohort study using public discharge data from the California Office of Statewide Health Planning and Development. Inpatients age 18–64 with community-onset sepsis at California hospitals in 2010 were identified by diagnosis codes. Results Controlling for demographics, comorbidities, infection source, and hospital characteristics, lack of insurance was associated with an adjusted odds ratio (OR) of 1.26 (absolute risk difference 4.75%, p Conclusions The association between lack of insurance and organ dysfunction on admission in community-onset sepsis suggests that lack of insurance may impede timely care for patients with community-onset infections.

A project involving 3 Plan-Do-Study-Act cycles was undertaken to improve testing for Clostridioides difficile at a Veterans Administration medical center. The Plan-Do-Study-Act process facilitated stakeholder engagement and allowed each successive intervention to build on the prior, resulting in a decline in the rate of hospital-onset C difficile infection.

Melioidosis is a potentially fatal infection caused by the bacteriumBurkholderia pseudomallei. Clinical diagnosis of melioidosis can be challenging since there is no pathognomonic clinical syndrome, and the organism is often misidentified by methods used routinely in clinical laboratories. Although the disease is more prevalent in Thailand and northern Australia, sporadic cases may be encountered in areas where it is not endemic, including the United States. Since the organism is considered a tier 1 select agent according to the Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service, clinical laboratories must be proficient at rapidly recognizing isolates suspicious forB. pseudomallei, be able to safely perform necessary rule-out tests, and to refer suspect isolates to Laboratory Response Network reference laboratories. In this minireview, we report a case of melioidosis encountered at our institution and discuss the laboratory challenges encountered when dealing with clinical isolates suspicious forB. pseudomalleior clinical specimens from suspected melioidosis cases.

Importance The Early Management Bundle for Severe Sepsis/Septic Shock (SEP-1) is a quality metric based on a care bundle for early sepsis management. Published evidence on the association of SEP-1 with mortality is mixed and largely excludes cases of hospital-onset sepsis. Objective To assess the association of the SEP-1 bundle with mortality and organ dysfunction in cohorts with hospital-onset or community-onset sepsis. Design, Setting, and Participants This retrospective cohort study used data from 4 University of California hospitals from October 1, 2014, to October 1, 2017. Adult inpatients with a diagnosis consistent with sepsis or disseminated infection and laboratory or vital signs meeting the Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock) criteria were divided into community-onset sepsis and hospital-onset sepsis cohorts based on whether time 0 of sepsis occurred after arrival in the emergency department or an inpatient area. Data were analyzed from April to October 2019. Additional analyses were performed from December 2019 to January 2020. Exposures Administration of SEP-1 and 4 individual bundle components (serum lactate level testing, blood culture, broad-spectrum intravenous antibiotic treatment, and intravenous fluid treatment). Main Outcomes and Measures The primary outcome was in-hospital mortality. The secondary outcome was days requiring vasopressor support, measured as vasopressor days. Results Among the 6404 patient encounters identified (3535 men [55.2%]; mean [SD] age, 64.0 [18.2] years), 2296 patients (35.9%) had hospital-onset sepsis. Among 4108 patients (64.1%) with community-onset sepsis, serum lactate level testing within 3 hours of time 0 was associated with reduced mortality (absolute difference, –7.61%; 95% CI, –14.70% to –0.54%). Blood culture (absolute difference, –1.10 days; 95% CI, –1.85 to –0.34 days) and broad-spectrum intravenous antibiotic treatment (absolute difference, –0.62 days; 95% CI, –1.02 to –0.22 days) were associated with fewer vasopressor days. Among patients with hospital-onset sepsis, broad-spectrum intravenous antibiotic treatment was the only bundle component significantly associated with any improved outcome (mortality difference, –5.20%; 95% CI, –9.84% to –0.56%). Care that was adherent to the complete SEP-1 bundle was associated with increased vasopressor days in patients with community-onset sepsis (absolute difference, 0.31 days; 95% CI, 0.11-0.51 days) but was not significantly associated with reduced mortality in either cohort (absolute difference, –0.07%; 95% CI, –3.02% to 2.88% in community-onset; absolute difference, –0.42%; 95% CI, –6.77% to 5.93% in hospital-onset). Conclusions and Relevance SEP-1–adherent care was not associated with improved outcomes of sepsis. Although multiple components of SEP-1 were associated with reduced mortality or decreased days of vasopressor therapy for patients who presented with sepsis in the emergency department, only broad-spectrum intravenous antibiotic treatment was associated with reduced mortality when time 0 occurred in an inpatient unit. Current sepsis quality metrics may need refinement.

BACKGROUND AND AIMS Risk factors for osteoporotic fracture as well as inpatient utilization and mortality have not been thoroughly studied in patients with cirrhosis. We analyzed data from a national database to determine fracture risk in patients with cirrhosis, specific risk factors, and the effect of fractures on health care utilization. METHODS We performed an observational study using serial cross-sectional data to examine fracture-related hospitalizations of patients with cirrhosis using the National Inpatient Sample from 2012 to 2013. We collected data on fracture-related hospitalizations and utilization in the form of length of stay (LOS), total hospital costs, and inpatient mortality. We used multivariate regression to determine risk factors for fracture and fracture-related mortality. RESULTS Patients with cirrhosis and an osteoporotic fracture had a mean LOS of 10.4 days and incurred $26,582 per hospitalization, which were statistically different from noncirrhotic patients with fracture (LOS: 6.60 d, cost: $17,918) and cirrhotic patients without fracture (LOS: 7.84 d, $18,912). Malnutrition was associated with increased odds of fracture [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.20-1.39] and inpatient mortality (OR, 1.40; 95% CI, 1.12-1.76). Obesity was protective against both fracture (OR, 0.78; 95% CI, 0.71-0.85) and fracture-related mortality (OR, 0.82; 95% CI, 0.59-1.14). CONCLUSIONS Hospitalizations for osteoporotic fractures in patients with cirrhosis are a significant source of health care burden and mortality. More attention should be paid to screening patients with cirrhosis for low bone mass. Malnutrition is associated with increased fracture risk and fracture-related mortality, representing a modifiable risk factor worthy of addressing in patients with cirrhosis.

The incidence of esophageal adenocarcinoma has increased dramatically in the United States and Europe since the 1970s without apparent cause. Although specific host factors can affect risk of disease, such a rapid increase in incidence must be predominantly environmental. In the stomach, infection with Helicobacter pylori has been linked to chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. However, the role of H. pylori in the development of esophageal adenocarcinoma is not well established. Meanwhile, several studies have established that a complex microbiome in the distal esophagus might play a more direct role. Transformation of the microbiome in precursor states to esophageal adenocarcinoma-reflux esophagitis and Barrett metaplasia-from a predominance of gram-positive bacteria to mostly gram-negative bacteria raises the possibility that dysbiosis is contributing to pathogenesis. However, knowledge of the microbiome in esophageal adenocarcinoma itself is lacking. Microbiome studies open a new avenue to the understanding of the etiology and pathogenesis of reflux disorders.

Background Every hour of delay between onset of sepsis and administration of the sepsis bundle increases sepsis mortality. Hospital-onset sepsis is known to have higher mortality than community-onset sepsis, but the differences in care between cases of hospital-onset and community-onset sepsis have not been characterized. The purpose of this study was to examine adherence to the sepsis bundle when sepsis arises in different areas of the hospital (ward, intensive care unit [ICU], or peri-operative area) compared with community-onset sepsis. Methods Retrospective cohort study using clinical data from four University of California hospitals. Admissions for sepsis from 2014 to 2016 were identified by diagnosis codes. Generalized linear models were used to estimate likelihood of adherence in terms of relative risk (RR). Time-to-event analysis involved Cox proportional hazards models and Kaplan–Meier curves. Results Overall, the sepsis bundle was administered in accordance with guidelines in 11.1% of cases. On multivariable analysis, cases of hospital-onset sepsis were less likely to receive the sepsis bundle within the recommended time frame (adjusted RR 0.57, P < 0.001) than were cases of community-onset sepsis, including a lower likelihood of having blood cultures drawn (adjusted RR 0.75, P < 0.001), serum lactate checked (adjusted RR 0.48, P < 0.001), or broad-spectrum antibiotics administered within 3 hours (adjusted RR 0.65, P < 0.001). Among the cases of hospital-onset sepsis, those arising in the ICU were more likely than those arising on the ward or in the perioperative area to receive the sepsis bundle within the recommended time frame (RR 1.83, P = 0.002). On time-to-event analysis, hospital-onset was associated with significant delays for all 3-hour bundle components except intravenous fluids. Conclusion Developing sepsis in one of the inpatient hospital areas was associated with a delay in guideline-adherent sepsis care. The ward and perioperative area experienced the longest delays. Further research is needed to determine whether these delays in care contribute to the increased mortality associated with hospital-onset sepsis. Disclosures All authors: No reported disclosures.

Although recent studies report a high prevalence of vitamin D deficiency in HIV-infected adults similar to that in the general population, metabolic complications of vitamin D deficiency may be worsened with HIV infection and remain insufficiently characterized. We conducted a retrospective cross-sectional cohort study to determine prevalence and correlates of vitamin D deficiency and hyperparathyroidism among HIV-infected patients attending an urban clinic. Vitamin D deficiency was defined as 25(OH)-vitamin D 65 pg/ml. We used the X2 test to compare proportions and logistic regression to assess for associations. Among 463 HIV-infected patients, the prevalence of vitamin D deficiency was 59%. The prevalence of hyperparathyroidism was 30% among patients with vitamin D deficiency, 23% among those with insufficiency, and 12% among those with sufficient vitamin D levels. Vitamin D deficiency was associated with increased odds of hyperparathyroidism. Severe vitamin D deficiency was associated with elevated alkaline phosphatase, a marker for increased bone turnover. Although efavirenz use was associated with vitamin D deficiency, and protease inhibitor use with decreased odds of vitamin D deficiency, there was no statistical difference in rates of hyperparathyroidism stratified by combination antiretroviral therapy (cART) use. Given the increased risk of osteopenia with HIV infection and cART use, vitamin D supplementation for all HIV-infected patients on cART should be prescribed in accordance with the 2011 Endocrine Society guidelines. In HIV-infected patients with severe vitamin D deficiency or hyperparathyroidism, screening for osteomalacia and osteopenia may be warranted.

Fungal infections in the central nervous system (CNS) are associated with significant morbidity and death. Transient fungemia in immunocompetent patients without any other risk factors for fungemia has been suggested as a possible mechanism that may lead to serious fungal ventriculoperitoneal (VP) shunt infections, but evidence is lacking. The clinical spectrum, diagnosis, and optimal therapy ofCyberlindnera fabianiiinfections remain to be determined. We describe the first case of CNS infection due toC. fabianiithat occurred in an immunocompetent adult with a VP shunt. Spontaneous translocation with yeast that is not part of the normal gastrointestinal flora in the setting of ingestion of multiple servings of a fermentation product was the likely source from whichCyberlindnera fabianiigained entrance into the VP shunt system, causing meningitis in this patient. The authors conclude that, in view of the high morbidity associated with yeast infection of the CNS, long-term antifungal therapy should be strongly considered in cases where the VP shunt cannot be completely removed. Transient fungemia may lead to invasive disease in an immunocompetent host with VP shunt, even in the absence of any other risk factors for fungemia and even after remote placement of the VP shunt.

The American Diabetes Association now recommends hemoglobin A(1c) (HbA(1c)) screening for the diagnosis of diabetes. It has been reported that HbA(1c) levels underestimate glycemic levels in HIV-infected persons. We examined the performance of HbA(1c) as a screening test for diabetes in a group of HIV-infected people without diabetes. We conducted a retrospective cross-sectional cohort study among HIV-infected patients determining the sensitivity and specificity of HbA(1c) as a screening test compared to fasting blood glucose (FBG). The effect of treatment regimen on the relationship between HbA(1c) and FBG was assessed by multiple linear regressions. Twenty-two of the 395 patients included in the study were newly diagnosed with diabetes based on FBG≥126 mg/dL. Using a cutoff of HbA(1c)≥6.5%, HbA(1c) had a sensitivity of 40.9% and specificity of 97.5% for identification of incident diabetes. At an HbA(1c) level of 5.8% the product of sensitivity and specificity was maximized, with values of 88.8% and 77.5% respectively. Higher mean cell volume (MCV) values (p=0.02) and current use of a non-nucleoside reverse transcriptase inhibitors (NNRTIs; p=0.02) significantly increased the slope, while PI use significantly decreased the slope (p0.001), of the linear regression of HbA(1c) compared to FBG. Tenofovir use did not significantly alter the slope or y-intercept of the line. Among HIV-infected nondiabetic patients, HbA(1c) is insensitive, although highly specific for diagnosing diabetes. Current antiretroviral (ART) use has significant and variable influence on the relationship between HbA(1c) and FBG. The use of HbA(1c) in conjunction with FBG may be the best modality to screen for diabetes.