A multi-center validation of the electronic health record admission source and discharge location fields against the clinical notes for identifying inpatients with long-term care facility exposure.

Identifying long-term care facility (LTCF)-exposed inpatients is important for infection control research and practice, but ascertaining LTCF exposure is challenging. Across a large validation study, electronic health record data fields identified 76% of LTCF-exposed patients compared to manual chart review. OBJECTIVE: Residence or recent stay in a long-term care facility (LTCF) is an important risk factor for antibiotic-resistant bacterial colonization. However, absent dedicated intake questionnaires or resource-intensive chart review, ascertaining LTCF exposure in inpatients is challenging. We aimed to validate the electronic health record (EHR) admission and discharge location fields against the clinical notes for identifying LTCF-exposed inpatients. METHODS: We conducted a retrospective study of 1020 randomly sampled adult admissions between 2016 and 2021 across 12 University of Maryland Medical System hospitals. Using study-developed guidelines, we categorized the following data for LTCF exposure: each admission's history & physical (H&P) note, each admission's EHR-extracted "Admission Source," and (3) the EHR-extracted admission and discharge locations for previous admissions (≤90 days). We estimated sensitivities, with 95% CIs, of H&P notes and of EHR admission/discharge location fields for detecting "current" and "any recent" (≤90 days, including current) LTCF exposure. RESULTS: For detecting current LTCF exposure, the sensitivity of the index admission's EHR-extracted "Admission Source" was 46% (95% CI: 35%­58%) and of the H&P note was 92% (83%­97%). For detecting any recent LTCF exposure, the sensitivity of "Admission Source" across the index and previous admissions was 32% (24%­41%), "Discharge Location" across previous admission(s) was 57% (47%­66%), and of the H&P note was 68% (59%­76%). The combined sensitivity of admission source and discharge location for detecting any recent LTCF exposure was 76% (67%­83%). CONCLUSIONS: The EHR-obtained admission source and discharge location fields identified 76% of LTCF-exposed patients compared to chart review but disproportionately missed currently exposed patients.

Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy.

Pregnant patients are at greater risk of hospitalization with severe COVID-19 than non-pregnant people. This was a retrospective observational cohort study of remnant clinical specimens from patients who visited acute care hospitals within the Johns Hopkins Health System in the Baltimore, MD-Washington DC, area between October 2020 and May 2022. Participants included confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant people and matched non-pregnant people (the matching criteria included age, race/ethnicity, area deprivation index, insurance status, and vaccination status to ensure matched demographics). The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant patients were at increased risk of hospitalization (odds ratio [OR] = 4.2; confidence interval [CI] = 2.0-8.6), intensive care unit admittance (OR = 4.5; CI = 1.2-14.2), and being placed on supplemental oxygen therapy (OR = 3.1; CI = 1.3-6.9). Individuals infected during their third trimester had higher mucosal anti-S IgG titers and lower viral RNA levels (P < 0.05) than those infected during their first or second trimesters. Pregnant individuals experiencing breakthrough infections due to the Omicron variant had reduced anti-S IgG compared to non-pregnant patients (P < 0.05). The observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity through booster vaccines may be important for the protection of this at-risk population.IMPORTANCEIn this retrospective observational cohort study, we analyzed remnant clinical samples from non-pregnant and pregnant individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who visited the Johns Hopkins Hospital System between October 2020 and May 2022. Disease severity, including intensive care unit admission, was greater among pregnant than non-pregnant patients. Vaccination reduced recovery of infectious virus and viral RNA levels in non-pregnant patients, but not in pregnant patients. In pregnant patients, increased nasopharyngeal viral RNA levels and recovery of infectious virus were associated with reduced mucosal IgG antibody responses, especially among women in their first trimester of pregnancy or experiencing breakthrough infections from Omicron variants. Taken together, this study provides insights into how pregnant patients are at greater risk of severe COVID-19. The novelty of this study is that it focuses on the relationship between the mucosal antibody response and its association with virus load and disease outcomes in pregnant people, whereas previous studies have focused on serological immunity. Vaccination status, gestational age, and SARS-CoV-2 omicron variant impact mucosal antibody responses and recovery of infectious virus from pregnant patients.

Understanding the role of antibiotic-associated adverse events in influencing antibiotic decision-making.

Objective: To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern. Design: Focus groups. Setting: Academic medical center. Participants: Medical and surgical house staff, attending physicians, and advanced practice practitioners. Methods: Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding. Results: Four focus groups were conducted (n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern. Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.

Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions.

OBJECTIVE: To evaluate the economic costs of reducing the University of Virginia Hospital's present "3-negative" policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. DESIGN: Cost-effective analysis. SETTINGS: The University of Virginia Hospital. PATIENTS: The study included data from 41,216 patients from 2015 to 2019. METHODS: We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. RESULTS: Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, -30 to 44; P < .001) and 17 (95% CI, -23 to 59; -10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592-$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522-$812,662) and 3-negative ($702,823; 95% CI, $577,277-$846,605). CONCLUSIONS: A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Epidemiology and Clinical Outcomes of Community-Acquired Acute Kidney Injury in the Emergency Department: A Multisite Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The prevalence of community-acquired acute kidney injury (CA-AKI) in the United States and its clinical consequences are not well described. Our objective was to describe the epidemiology of CA-AKI and the associated clinical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 178,927 encounters by 139,632 adults at 5 US emergency departments (EDs) between July 1, 2017, and December 31, 2022. PREDICTORS: CA-AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine (Scr)-based criteria. OUTCOMES: For encounters resulting in hospitalization, the in-hospital trajectory of AKI severity, dialysis initiation, intensive care unit (ICU) admission, and death. For all encounters, occurrence over 180 days of hospitalization, ICU admission, new or progressive chronic kidney disease, dialysis initiation, and death. ANALYTICAL APPROACH: Multivariable logistic regression analysis to test the association between CA-AKI and measured outcomes. RESULTS: For all encounters, 10.4% of patients met the criteria for any stage of AKI on arrival to the ED. 16.6% of patients admitted to the hospital from the ED had CA-AKI on arrival to the ED. The likelihood of AKI recovery was inversely related to CA-AKI stage on arrival to the ED. Among encounters for hospitalized patients, CA-AKI was associated with in-hospital dialysis initiation (OR, 6.2; 95% CI, 5.1-7.5), ICU admission (OR, 1.9; 95% CI, 1.7-2.0), and death (OR, 2.2; 95% CI, 2.0-2.5) compared with patients without CA-AKI. Among all encounters, CA-AKI was associated with new or progressive chronic kidney disease (OR, 6.0; 95% CI, 5.6-6.4), dialysis initiation (OR, 5.1; 95% CI, 4.5-5.7), subsequent hospitalization (OR, 1.1; 95% CI, 1.1-1.2) including ICU admission (OR, 1.2; 95% CI, 1.1-1.4), and death (OR, 1.6; 95% CI, 1.5-1.7) during the subsequent 180 days. LIMITATIONS: Residual confounding. Study implemented at a single university-based health system. Potential selection bias related to exclusion of patients without an available baseline Scr measurement. Potential ascertainment bias related to limited repeat Scr data during follow-up after an ED visit. CONCLUSIONS: CA-AKI is a common and important entity that is associated with serious adverse clinical consequences during the 6-month period after diagnosis. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) is a condition characterized by a rapid decline in kidney function. There are many causes of AKI, but few studies have examined how often AKI is already present when patients first arrive to an emergency department seeking medical attention for any reason. We analyzed approximately 175,000 visits to Johns Hopkins emergency departments and found that AKI is common on presentation to the emergency department and that patients with AKI have increased risks of hospitalization, intensive care unit admission, development of chronic kidney disease, requirement of dialysis, and death in the first 6 months after diagnosis. AKI is an important condition for health care professionals to recognize and is associated with serious adverse outcomes.

Risk Factors for Hospitalization and Effect of Immunosuppression on Clinical Outcomes Among an Urban Cohort of Patients With Mpox.

Background: During the 2022 mpox outbreak most patients were managed as outpatients, but some required hospitalization. Uncontrolled human immunodeficiency virus (HIV) has been identified as a risk factor for severe mpox. Methods: Patients with mpox diagnosed or treated within the Johns Hopkins Health System between 1 June and 15 December 2022 were included. The primary outcome of interest was risk of hospitalization. Demographic features, comorbid conditions, treatment, and clinical outcomes were determined. Results: A total of 353 patients were tested or treated for mpox; 100 had mpox diagnosed or treated (median age, 35.3 years; 97.0% male; 57.0% black and 10.0% Hispanic; 46.0% people with HIV [PWH]). Seventeen patients (17.0%) required hospitalization, 10 of whom were PWH. Age >40 years, race, ethnicity, HIV status, insurance status, and body mass index >30 (calculated as weight in kilograms divided by height in meters squared) were not associated with hospitalization. Eight of 9 patients (88.9%) with immunosuppression were hospitalized. Immunosuppression was associated with hospitalization in univariate (odds ratio, 69.3 [95% confidence interval, 7.8-619.7]) and adjusted analysis (adjusted odds ratio, 94.8 [8.5-1060.1]). Two patients (11.8%) who were hospitalized required intensive care unit admission and died; both had uncontrolled HIV infection and CD4 T-cell counts <50/µL. Median cycle threshold values for the first positive mpox virus sample did not differ between those who were hospitalized and those who were not. Conclusions: Immunosuppression was a significant risk factor for hospitalization with mpox. PWH with CD4 T-cell counts <50/µL are at high risk of death due to mpox infection. Patients who are immunosuppressed should be considered for early and aggressive treatment of mpox, given the increased risk of hospitalization.

Severity outcomes associated with SARS-CoV-2 XBB variants, an observational analysis.

The rapidity with which SARS-CoV-2 XBB variants rose to predominance has been alarming. We used a large cohort of patients diagnosed with Omicron infections between September 2022 and mid-February 2023 to evaluate the likelihood of admission or need for supplemental oxygen in patients infected with XBB variants. Our data showed no significant association between XBB or XBB.1.5 infections and admissions. Older age groups, lack of vaccination, immunosuppression and underlying heart, kidney, and lung disease showed significant associations with hospitalization.

An Electronic Algorithm to Identify Vancomycin-Associated Acute Kidney Injury.

Background: The burden of vancomycin-associated acute kidney injury (V-AKI) is unclear because it is not systematically monitored. The objective of this study was to develop and validate an electronic algorithm to identify cases of V-AKI and to determine its incidence. Methods: Adults and children admitted to 1 of 5 health system hospitals from January 2018 to December 2019 who received at least 1 dose of intravenous (IV) vancomycin were included. A subset of charts was reviewed using a V-AKI assessment framework to classify cases as unlikely, possible, or probable events. Based on review, an electronic algorithm was developed and then validated using another subset of charts. Percentage agreement and kappa coefficients were calculated. Sensitivity and specificity were determined at various cutoffs, using chart review as the reference standard. For courses ≥48 hours, the incidence of possible or probable V-AKI events was assessed. Results: The algorithm was developed using 494 cases and validated using 200 cases. The percentage agreement between the electronic algorithm and chart review was 92.5% and the weighted kappa was 0.95. The electronic algorithm was 89.7% sensitive and 98.2% specific in detecting possible or probable V-AKI events. For the 11 073 courses of ≥48 hours of vancomycin among 8963 patients, the incidence of possible or probable V-AKI events was 14.0%; the V-AKI incidence rate was 22.8 per 1000 days of IV vancomycin therapy. Conclusions: An electronic algorithm demonstrated substantial agreement with chart review and had excellent sensitivity and specificity in detecting possible or probable V-AKI events. The electronic algorithm may be useful for informing future interventions to reduce V-AKI.

Implementing and validating a home-infusion central-line-associated bloodstream infection surveillance definition.

OBJECTIVE: Central-line-associated bloodstream infection (CLABSI) surveillance in home infusion therapy is necessary to track efforts to reduce infections, but a standardized, validated, and feasible definition is lacking. We tested the validity of a home-infusion CLABSI surveillance definition and the feasibility and acceptability of its implementation. DESIGN: Mixed-methods study including validation of CLABSI cases and semistructured interviews with staff applying these approaches. SETTING: This study was conducted in 5 large home-infusion agencies in a CLABSI prevention collaborative across 14 states and the District of Columbia. PARTICIPANTS: Staff performing home-infusion CLABSI surveillance. METHODS: From May 2021 to May 2022, agencies implemented a home-infusion CLABSI surveillance definition, using 3 approaches to secondary bloodstream infections (BSIs): National Healthcare Safety Program (NHSN) criteria, modified NHSN criteria (only applying the 4 most common NHSN-defined secondary BSIs), and all home-infusion-onset bacteremia (HiOB). Data on all positive blood cultures were sent to an infection preventionist for validation. Surveillance staff underwent semistructured interviews focused on their perceptions of the definition 1 and 3-4 months after implementation. RESULTS: Interrater reliability scores overall ranged from κ = 0.65 for the modified NHSN criteria to κ = 0.68 for the NHSN criteria to κ = 0.72 for the HiOB criteria. For the NHSN criteria, the agency-determined rate was 0.21 per 1,000 central-line (CL) days, and the validator-determined rate was 0.20 per 1,000 CL days. Overall, implementing a standardized definition was thought to be a positive change that would be generalizable and feasible though time-consuming and labor intensive. CONCLUSIONS: The home-infusion CLABSI surveillance definition was valid and feasible to implement.

Healthcare personnel interactive pathogen exposure response system.

Exposure investigations are labor intensive and vulnerable to recall bias. We developed an algorithm to identify healthcare personnel (HCP) interactions from the electronic health record (EHR), and we evaluated its accuracy against conventional exposure investigations. The EHR algorithm identified every known transmission and used ranking to produce a manageable contact list.

Risk-factor analysis for extended-spectrum beta-lactamase-producing Enterobacterales colonization or infection: Evaluation of a novel approach to assess local prevalence as a risk factor.

OBJECTIVE: To explore an approach to identify the risk of local prevalence of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) on ESBL-E colonization or infection and to reassess known risk factors. DESIGN: Case-control study. SETTING: Johns Hopkins Health System emergency departments (EDs) in the Baltimore-Washington, DC, region. PATIENTS: Patients aged ≥18 years with a culture growing Enterobacterales between April 2019 and December 2021. Cases had a culture growing an ESBL-E. METHODS: Addresses were linked to Census Block Groups and placed into communities using a clustering algorithm. Prevalence in each community was estimated using the proportion of ESBL-E among Enterobacterales isolates. Logistic regression was used to determine risk factors for ESBL-E colonization or infection. RESULTS: ESBL-E were detected in 1,167 of 11,224 patients (10.4%). Risk factors included a history of ESBL-E in the prior 6 months (aOR, 20.67; 95% CI, 13.71-31.18), exposure to a skilled nursing or long-term care facility (aOR, 1.64; 95% CI, 1.37-1.96), exposure to a third-generation cephalosporin (aOR, 1.79; 95% CI, 1.46-2.19), exposure to a carbapenem (aOR, 2.31; 95% CI, 1.68-3.18), or exposure to a trimethoprim-sulfamethoxazole (aOR, 1.54; 95% CI, 1.06-2.25) within the prior 6 months. Patients were at lower risk if their community had a prevalence <25th percentile in the prior 3 months (aOR, 0.83; 95% CI, 0.71-0.98), 6 months (aOR, 0.83; 95% CI, 0.71-0.98), or 12 months (aOR, 0.81; 95% CI, 0.68-0.95). There was no association between being in a community in the >75th percentile and the outcome. CONCLUSIONS: This method of defining the local prevalence of ESBL-E may partially capture differences in the likelihood of a patient having an ESBL-E.

Multiple models for outbreak decision support in the face of uncertainty.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

Reduced control of SARS-CoV-2 infection is associated with lower mucosal antibody responses in pregnant women.

Importance: Pregnant women are at increased risk of severe COVID-19, but the contribution of viral RNA load, the presence of infectious virus, and mucosal antibody responses remain understudied. Objective: To evaluate the association of COVID-19 outcomes following confirmed infection with vaccination status, mucosal antibody responses, infectious virus recovery and viral RNA levels in pregnant compared with non-pregnant women. Design: A retrospective observational cohort study of remnant clinical specimens from SARS-CoV-2 infected patients between October 2020-May 2022. Setting: Five acute care hospitals within the Johns Hopkins Health System (JHHS) in the Baltimore, MD-Washington, DC area. Participants: Participants included confirmed SARS-CoV-2 infected pregnant women and matched non-pregnant women (matching criteria included age, race/ethnicity, and vaccination status). Exposure: SARS-CoV-2 infection, with documentation of SARS-CoV-2 mRNA vaccination. Main Outcomes: The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. Clinical outcomes were compared using odds ratios (OR), and measures of virus and antibody were compared using either Fisher's exact test, two-way ANOVA, or regression analyses. Results were stratified according to pregnancy, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant. Resultss: A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant women were at increased risk of hospitalization (OR = 4.2; CI = 2.0-8.6), ICU admittance, (OR = 4.5; CI = 1.2-14.2), and of being placed on supplemental oxygen therapy (OR = 3.1; CI =13-6.9). An age-associated decrease in anti-S IgG titer and corresponding increase in viral RNA levels (P< 0.001) was observed in vaccinated pregnant, but not non-pregnant, women. Individuals in their 3rd trimester had higher anti-S IgG titers and lower viral RNA levels (P< 0.05) than those in their 1st or 2nd trimesters. Pregnant individuals experiencing breakthrough infections due to the omicron variant had reduced anti-S IgG compared to non-pregnant women (P< 0.05). Conclusions and Relevance: In this cohort study, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant were each identified as drivers of differences in mucosal anti-S IgG responses in pregnant compared with non-pregnant women. Observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity may be important for protection of this at-risk population.

Renal outcomes following intravenous contrast administration in patients with acute kidney injury: a multi-site retrospective propensity-adjusted analysis.

PURPOSE: Evidence of an association between intravenous contrast media (CM) and persistent renal dysfunction is lacking for patients with pre-existing acute kidney injury (AKI). This study was designed to determine the association between intravenous CM administration and persistent AKI in patients with pre-existing AKI. METHODS: A retrospective propensity-weighted and entropy-balanced observational cohort analysis of consecutive hospitalized patients ≥ 18 years old meeting Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based criteria for AKI at time of arrival to one of three emergency departments between 7/1/2017 and 6/30/2021 who did or did not receive intravenous CM. Outcomes included persistent AKI at hospital discharge and initiation of dialysis within 180 days of index encounter. RESULTS: Our analysis included 14,449 patient encounters, with 12.8% admitted to the intensive care unit (ICU). CM was administered in 18.4% of all encounters. AKI resolved prior to hospital discharge for 69.1%. No association between intravenous CM administration and persistent AKI was observed after unadjusted multivariable logistic regression modeling (OR 1; 95% CI 0.89-1.11), propensity weighting (OR 0.93; 95% CI 0.83-1.05), and entropy balancing (OR 0.94; 95% CI 0.83-1.05). Sub-group analysis in those admitted to the ICU yielded similar results. Initiation of dialysis within 180 days was observed in 5.4% of the cohort. An association between CM administration and increased risk of dialysis within 180 days was not observed. CONCLUSION: Among patients with pre-existing AKI, contrast administration was not associated with either persistent AKI at hospital discharge or initiation of dialysis within 180 days. Current consensus recommendations for use of intravenous CM in patients with stable renal disease may also be applied to patients with pre-existing AKI.

Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization.

BACKGROUND: The variant of concern Omicron has become the sole circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021-January 2022. This study compared the clinical outcomes in patients infected with different Omicron subvariants and the relative viral loads and recovery of infectious virus from upper respiratory specimens. METHODS: SARS-CoV-2-positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole-genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared with infections with BA.1. Cycle threshold (Ct) values and the recovery of infectious virus on the VeroTMPRSS2 cell line from clinical specimens were compared. RESULTS: BA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and coronavirus disease 2019 (COVID-19)-related hospitalizations at the Johns Hopkins system. After a peak in January, cases decreased in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct value when compared with other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values <20. CONCLUSIONS: Omicron subvariants continue to be associated with a relatively high rate of polymerase chain reaction (PCR) positivity and hospital admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves.

SARS-CoV-2 reinfections during the Delta and Omicron waves.

BACKGROUNDIncreased SARS-CoV-2 reinfection rates have been reported recently, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection. In this study, we used Johns Hopkins SARS-CoV-2 genomic surveillance data to evaluate the frequency of sequencing-validated, confirmed, and inferred reinfections between March 2020 and July 2022.METHODSPatients who had 2 or more positive SARS-CoV-2 tests in our system, with samples sequenced as a part of our surveillance efforts, were identified as the cohort for our study. SARS-CoV-2 genomes of patients' initial and later samples were compared.RESULTSA total of 755 patients (920 samples) had a positive test at least 90 days after the initial test, with a median time between tests of 377 days. Sequencing was attempted on 231 samples and was successful in 127. Rates of successful sequencing spiked during the Omicron surge; there was a higher median number of days from initial infection in these cases compared with those with failed sequences. A total of 122 (98%) patients showed evidence of reinfection; 45 of these patients had sequence-validated reinfection and 77 had inferred reinfections (later sequencing showed a clade that was not circulating when the patient was initially infected). Of the 45 patients with sequence-validated reinfections, 43 (96%) had reinfections that were caused by the Omicron variant, 41 (91%) were symptomatic, 32 (71%) were vaccinated prior to the second infection, 6 (13%) were immunosuppressed, and only 2 (4%) were hospitalized.CONCLUSIONSequence-validated reinfections increased with the Omicron surge but were generally associated with mild infections.FUNDINGFunding was provided by the Johns Hopkins Center of Excellence in Influenza Research and Surveillance (HHSN272201400007C), CDC (75D30121C11061), Johns Hopkins University President's Fund Research Response, Johns Hopkins Department of Pathology, and the Maryland Department of Health.

Omicron Subvariants: Clinical, Laboratory, and Cell Culture Characterization.

Background: The variant of concern, Omicron, has become the sole circulating SARS-CoV-2 variant for the past several months. Omicron subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 evolved over the time, with BA.1 causing the largest wave of infections globally in December 2021- January 2022. In this study, we compare the clinical outcomes in patients infected with different Omicron subvariants and compare the relative viral loads, and recovery of infectious virus from upper respiratory specimens. Methods: SARS-CoV-2 positive remnant clinical specimens, diagnosed at the Johns Hopkins Microbiology Laboratory between December 2021 and July 2022, were used for whole genome sequencing. The clinical outcomes of infections with Omicron subvariants were compared to infections with BA.1. Cycle threshold values (Ct) and the recovery of infectious virus on VeroTMPRSS2 cell line from clinical specimens were compared. Results: The BA.1 was associated with the largest increase in SARS-CoV-2 positivity rate and COVID-19 related hospitalizations at the Johns Hopkins system. After a peak in January cases fell in the spring, but the emergence of BA.2.12.1 followed by BA.5 in May 2022 led to an increase in case positivity and admissions. BA.1 infections had a lower mean Ct when compared to other Omicron subvariants. BA.5 samples had a greater likelihood of having infectious virus at Ct values less than 20. Conclusions: Omicron subvariants continue to associate with a relatively high positivity and admissions. The BA.5 infections are more while BA.2 infections are less likely to have infectious virus, suggesting potential differences in infectibility during the Omicron waves. Funding: Centers for Disease Control and Prevention contract 75D30121C11061, NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, and The Modeling Infectious Diseases in Healthcare Network (MInD) under awards U01CK000589.

Prospective, multi-site study of patient outcomes after implementation of the TREWS machine learning-based early warning system for sepsis.

Early recognition and treatment of sepsis are linked to improved patient outcomes. Machine learning-based early warning systems may reduce the time to recognition, but few systems have undergone clinical evaluation. In this prospective, multi-site cohort study, we examined the association between patient outcomes and provider interaction with a deployed sepsis alert system called the Targeted Real-time Early Warning System (TREWS). During the study, 590,736 patients were monitored by TREWS across five hospitals. We focused our analysis on 6,877 patients with sepsis who were identified by the alert before initiation of antibiotic therapy. Adjusting for patient presentation and severity, patients in this group whose alert was confirmed by a provider within 3 h of the alert had a reduced in-hospital mortality rate (3.3%, confidence interval (CI) 1.7, 5.1%, adjusted absolute reduction, and 18.7%, CI 9.4, 27.0%, adjusted relative reduction), organ failure and length of stay compared with patients whose alert was not confirmed by a provider within 3 h. Improvements in mortality rate (4.5%, CI 0.8, 8.3%, adjusted absolute reduction) and organ failure were larger among those patients who were additionally flagged as high risk. Our findings indicate that early warning systems have the potential to identify sepsis patients early and improve patient outcomes and that sepsis patients who would benefit the most from early treatment can be identified and prioritized at the time of the alert.