Background The relationship between common patient characteristics, such as sex and metabolic comorbidities, and mortality from 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. Methods We 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. Results Among 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 only a risk factor 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 ≤ 0.002). Conclusions Hospitalized 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.

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’s 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.

IMPORTANCEThe 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 PARTICIPANTSThis 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 MEASURESThe 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 reduc...

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 ( p < 0.001), 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.

With the development of culture-independent technique, a complex microbiome has been established and described in the distal esophagus. Over recent decades, the incidence of esophageal adenocarcinoma (EAC)—a relatively rare cancer with high mortality—has increased dramatically in the United States. Several studies documenting an altered microbiome associated with EAC and its precedents (i.e., Barrett’s esophagus and reflux esophagitis) suggest that dysbiosis may be contributing to carcinogenesis, potentially mediated by interactions with toll-like receptors. Investigations attempting to associate viruses, in particular human papilloma virus, with EAC have not been as consistent. Regardless, currently available data is cross-sectional and therefore cannot prove causal relationships. Prospectively, microbiome studies open a new avenue to the understanding of the etiology and pathogenesis of reflux disorders and EAC.

bMelioidosis is a potentially fatal infection caused by the bacterium Burkholderia 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 for B. 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 for B. pseudomallei or clinical specimens from suspected melioidosis cases. CASEA 67-year-old Filipino woman with a previous history of treated tuberculosis, hypertension, type 2 diabetes, coronary artery disease, and complete heart block requiring a pacemaker and drug-eluting stent that was placed 4 months earlier presented to an outside hospital with 2 weeks of progressive left lower quadrant abdominal pain, chills, and subjective fever. She was evaluated in different emergency departments for similar complaints on two occasions in the preceding week, but was discharged home. She was admitted to an outside hospital on this visit and computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed an 8 by 8 by 8 mm suprarenal saccular aneurysm arising from the posterior aortic wall with surrounding inflammation. Blood cultures drawn in the emergency department grew a Gram-negative rod, which was identified by the Vitek 2 (bioMérieux, Durham NC) as Burkholderia pseudomallei. This identification was confirmed several weeks later by the Centers for Disease Control and Prevention (CDC). Transthoracic echocardiography showed no vegetation. The patient was treated with meropenem 1 g intravenously (i.v.) every 8 hours (q8h). Follow-up CT scans performed 9 days after presentation showed that the mycotic aneurysm had enlarged to 13 by 24 by 20 mm and revealed a second aneurysm of the lateral wall of the aorta measuring 4 by 4 mm.The patient was transferred to our institution for surgical evaluation. On arrival, two sets of blood cultures (BD Bactec FX system; Becton, Dickinson and Company, NJ) were collected. Within 48 h of transfer, the patient underwent surgical excision of the mycotic aneurysm and reconstruction of her aorta using bioprosthetic homografts. During the procedure, the aneurysm was found to have ruptured, with the resulting pseudoaneurysm encased in inflammatory material and purulent fluid. Intraoperative samples from t...

Background: Hospitalized patients with SARS-CoV-2 infection (COVID-19) often receive antibiotics for suspected bacterial co-infection. We estimated the incidence of bacterial co-infection and secondary infection in COVID-19 using clinical diagnoses to determine how frequently antibiotics are administered when bacterial infection is absent. Methods: We performed a retrospective cohort study of inpatients with COVID-19 present on admission to hospitals in the Premier Healthcare Database between April – June 2020. Bacterial infections were defined using ICD-10-CM diagnosis codes and associated “present on admission” coding. Co-infections were defined by bacterial infection present on admission, while secondary infections were defined by bacterial infection that developed after admission. Co-infection and secondary infection were not mutually exclusive. Results: 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% patients receiving steroids in the first 2 days of hospitalization, 9.9% receiving tocilizumab in the first 2 days of hospitalization, and 10.3% patients receiving both. After adjusting for patient and hospital characteristics, bacterial co-infection (aRR 1.15; 95% CI, 1.11 – 1.20) and secondary infection (aRR 1.93; 95% CI, 1.82 – 2.04) were both independently associated with increased mortality. Conclusions: Though 1 in 5 inpatients with COVID-19 present 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.

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.