Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

The Epidemiology of Respiratory Syncytial Virus in New York City during the Coronavirus Disease-2019 Pandemic Compared with Previous Years.

Fewer respiratory syncytial virus infections were observed in 2020-2021 with interseasonal resurgence. Children were more likely to have severe disease with less known risk factors in comparison with controls from 2018-2019. The overall codetection rates were similar, but with higher parainfluenza, rhinovirus/enterovirus, and lower influenza proportions compared with previous seasons.

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Discriminating Multisystem Inflammatory Syndrome in Children Requiring Treatment from Common Febrile Conditions in Outpatient Settings.

OBJECTIVES: To examine whether patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated well-defined clinical features distinct from other febrile outpatients, given the difficulties of seeing acute care visits during the severe acute respiratory syndrome coronavirus 2 pandemic and the risks associated with both over- and underdiagnosis of MIS-C. STUDY DESIGN: This case-controlled study compared patients diagnosed with and treated for MIS-C at a large urban children's hospital with patients evaluated for fever at outpatient acute care visits during the peak period of MIS-C. Symptomatology and available objective data were extracted. Comparisons were performed using t tests with corrections for multiple comparisons, and multivariable logistic regression to obtain ORs. RESULTS: We identified 44 patients with MIS-C between April 16 and June 10, 2020. During the same period, 181 pediatric patients were evaluated for febrile illnesses in participating outpatient clinics. Patients with MIS-C reported greater median maximum reported temperature height (40°C vs 38.9, P < .0001), and increased frequency of abdominal pain (OR 12.5, 95% CI [1.65-33.24]), neck pain (536.5, [2.23-129,029]), conjunctivitis (31.3, [4.6-212.8]), oral mucosal irritation (11.8, [1.4-99.4]), extremity swelling or rash (99.9, [5-1960]), and generalized rash (7.42, [1.6-33.2]). Patients with MIS-C demonstrated lower absolute lymphocyte (P < .0001) and platelet counts (P < .05) and greater C-reactive protein concentrations (P < .001). CONCLUSIONS: Patients treated for MIS-C due to concern for potential cardiac injury show combinations of features distinct from other febrile patients seen in outpatient clinics during the same period.

Acute Hepatitis Is a Prominent Presentation of the Multisystem Inflammatory Syndrome in Children: A Single-Center Report.

BACKGROUND AND AIMS: A newly recognized multisystem inflammatory syndrome in children (MIS-C) has had a paradigm-shifting effect on the perception of severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) illness severity in children. We report the clinical and biochemical features of liver involvement, and the comorbidities that present with hepatitis, in a substantial cohort of patients. APPROACH AND RESULTS: This is a retrospective cohort study of 44 patients with MIS-C admitted at Morgan Stanley Children's Hospital of New York-Presbyterian during April and May 2020. We evaluated the number of patients who developed hepatitis and examined both demographics and inflammatory laboratory values to ascertain those that were at higher risk for liver involvement and more severe disease. Hepatitis was present in 19 subjects (43%) and was associated with more severe disease. Persons with hepatitis had significantly higher rates of shock at presentation (21.1% vs. 0%; P = 0.008), greater respiratory support requirement (42.1% vs. 12%; P = 0.005), and longer hospitalization times (median, 7 [interquartile range {IQR}, 5, 10] vs. 4 days [IQR, 3.5, 6.5]; P < 0.05). Patients with hepatitis also had significantly higher levels of ferritin (706.9 vs. 334.2 mg/mL; P < 0.01), interleukin-6 (233.9 vs. 174.7 pg/mL; P < 0.05), troponin (83.0 vs. 28.5 ng/L; P < 0.05), and B-type natriuretic peptide (7,424.5 vs. 3,209.5 pg/mL; P < 0.05). The single patient with liver failure also developed multiorgan failure requiring vasopressors, hemodialysis, and mechanical ventilation. All patients were discharged, though >50% had persistent hepatitis up to 1 month after discharge. CONCLUSIONS: Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests in many. Despite the positive outcomes reported here, close follow-up is warranted given the limited knowledge of the long-term impact of SARS-CoV-2 on the liver.

Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children's Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up.

OBJECTIVES: The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome. DATA SOURCES: The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods. DATA SYNTHESIS: Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay. CONCLUSIONS: This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.

The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study.

BACKGROUND: The need for early antibiotics in the intensive care unit (ICU) is often balanced against the goal of antibiotic stewardship. Long-course antibiotics increase the burden of antimicrobial resistance within colonizing gut bacteria, but the dynamics of this process are not fully understood. We sought to determine how short-course antibiotics affect the antimicrobial resistance phenotype and genotype of colonizing gut bacteria in the ICU by performing a prospective cohort study with assessments of resistance at ICU admission and exactly 72 h later. METHODS: Deep rectal swabs were performed on 48 adults at the time of ICU admission and exactly 72 h later, including patients who did and did not receive antibiotics. To determine resistance phenotype, rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, Gram-negative bacterial isolates were cultured against relevant antibiotics. To determine resistance genotype, quantitative PCR (qPCR) was performed from rectal swabs for 87 established resistance genes. Within-individual changes in antimicrobial resistance were calculated based on culture and qPCR results and correlated with exposure to relevant antibiotics (e.g., did ß-lactam antibiotic exposure associate with a detectable change in ß-lactam resistance over this 72-h period?). RESULTS: Of 48 ICU patients, 41 (85%) received antibiotics. Overall, there was no increase in the antimicrobial resistance profile of colonizing gut bacteria during the 72-h study period. There was also no increase in antimicrobial resistance after stratification by receipt of antibiotics (i.e., no detectable increase in ß-lactam, vancomycin, or macrolide resistance regardless of whether patients received those same antibiotics). This was true for both culture and PCR. Antimicrobial resistance pattern at ICU admission strongly predicted resistance pattern after 72 h. CONCLUSIONS: Short-course ICU antibiotics made little detectable difference in the antimicrobial resistance pattern of colonizing gut bacteria over 72 h in the ICU. This provides an improved understanding of the dynamics of antimicrobial resistance in the ICU and some reassurance that short-course antibiotics may not adversely impact the stewardship goal of reducing antimicrobial resistance.

Novel Strategies for Predicting Healthcare-Associated Infections at Admission: Implications for Nursing Care.

BACKGROUND: Accurate, real-time models to predict hospital adverse events could facilitate timely and targeted interventions to improve patient outcomes. Advances in computing enable the use of supervised machine learning (SML) techniques to predict hospital-onset infections. OBJECTIVES: The purpose of this study was to trial SML methods to predict urinary tract infections (UTIs) during inpatient hospitalization at the time of admission. METHODS: In a large cohort of adult hospitalizations in three New York City acute care facilities (N = 897,344), we used two SML methods-neural networks and decision trees-to predict having a hospital-onset UTI using data available and accessible on the first day of admission at healthcare facilities in the United States. RESULTS: Performance for both neural network and decision tree models were superior compared to logistic regression methods. The decision tree model had a higher sensitivity compared to neural network, but a lower specificity. DISCUSSION: SML methods show potential for automated accurate UTI risk stratification using electronic data routinely available at admission; this could relieve nurses from the burden of having to complete and document additional risk assessment forms in the electronic medical record. Future studies should pilot and test interventions linked to the risk stratification results, such as short nursing educational modules or alerts triggered for high-risk patients.

The Association Between the Frequency of Interruptions in Antibiotic Exposure and the Risk of Health Care-Associated Clostridiodes difficile Infection.

BACKGROUND: Although antibiotic use is an established risk factor for health care-associated Clostridiodes difficile infection, estimates of the association between infection and antibiotic use vary, depending upon how antibiotic exposure is measured. OBJECTIVES: The purpose of this study was to explore the association between the frequency of interruptions in antibiotic exposure and the risk of health care-associated C difficile infection. METHODS: A retrospective chart review cohort study was conducted of all inpatients between 2011and 2016 from a single academic health center who received at least 1 dose of a systemic antibacterial for a cumulative duration of >3 days and ≤30 days. The measures of antibiotic exposure examined were duration-cumulative total calendar days of antibiotics therapy-and continuity-the frequency of interruptions in antibiotic exposure that was defined as the number of antibiotic treatment courses. RESULTS: A total of 52,445/227,967 (23%) patients received antibacterial therapy for >3 days and ≤30 days during their hospitalization. Of these, 1161 out of 52,445 (2.21%) were patients with health care-associated C difficile infection. An adjusted multivariable logistic regression analysis revealed that the risk of C difficile increased with longer cumulative days (odds ratio = 2.7; comparison of >12 days to ≤5 days) and fewer interruptions of antibiotic treatment (odds ratio = 0.78; comparison of >3 discrete antibiotic treatment courses to 1 course or continuous antibiotic treatment course; all P values < 0.05). CONCLUSIONS: For patients who received the same number of cumulative days of therapy, the patients who had more frequently interrupted courses of antibiotic therapy were less likely to experience health care-associated C difficile infection. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Disseminated trichosporonosis with atypical histologic findings in a patient with acute lymphocytic leukemia.

We report a case of disseminated Trichosporon asahii in a patient on systemic antifungal therapy who presented with multiple cutaneous nodules suggestive of fungal infection. Histologic features resembled neutrophilic eccrine hidradenitis but staining with periodic acid-Schiff and Gomori methenamine silver confirmed the clinical diagnosis. This case highlights the importance of maintaining suspicion for trichosporonosis and contextualizing histologic findings within the underlying clinical picture.

Decision-Making Around Positive Tracheal Aspirate Cultures: The Role of Neutrophil Semiquantification in Antibiotic Prescribing.

OBJECTIVES: Ventilator-associated infections are a major contributor to antibiotic use in the PICU. Quantitative or semiquantitative assessment of neutrophils (microscopic purulence) is routinely reported in positive cultures from tracheal aspirates. The role of microscopic purulence in guiding antibiotic therapy or its association with symptoms of ventilator-associated infections is less described in children. We examine microscopic purulence as an independent predictor of antibiotic use for positive tracheal aspirate cultures in the PICU. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Children admitted to the PICU, neuro-PICU, or cardiac PICU with a positive tracheal aspirate culture from January 1, 2016, to December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Positive tracheal aspirate cultures were reviewed. The outcome variable was antibiotic treatment that targeted the positive tracheal aspirate culture. The predictor variable was microscopic purulence, defined as moderate or many neutrophils on Gram stain report. Competing predictors included demographics, comorbidities, vital signs changes, respiratory support, and laboratory values. Of 361 positive cultures in the cohort, 81 (22%) were treated with antibiotics. Positive cultures with microscopic purulence were targeted for therapy more frequently (30% vs 11%). Microscopic purulence was the strongest predictor for antibiotic therapy (odds ratio, 3.3; 95% CI, 1.6-6.8) compared with fever (odds ratio, 2.0; 95% CI, 1.0-4.1) or increased respiratory support (odds ratio, 2.3; 95% CI, 1.2-4.3). There was no significant variation in symptomatology between microscopic purulence reported as moderate or many versus other (e.g., fever -24% vs 22%, increased respiratory support -36% vs 28%). Microscopic purulence was less prevalent with longer ventilator durations at the time of sampling. CONCLUSIONS: Microscopic purulence was an independent predictor of antibiotic therapy for positive tracheal aspirate cultures in our PICUs. However, microscopic purulence was not associated with clinical symptomatology.

Comparison of Measures to Predict Mortality and Length of Stay in Hospitalized Patients.

BACKGROUND: Patient risk adjustment is critical for hospital benchmarking and allocation of healthcare resources. However, considerable heterogeneity exists among measures. OBJECTIVES: The performance of five measures was compared to predict mortality and length of stay (LOS) in hospitalized adults using claims data; these include three comorbidity composite scores (Charlson/Deyo age-comorbidity score, V W Elixhauser comorbidity score, and V W Elixhauser age-comorbidity score), 3 M risk of mortality (3 M ROM), and 3 M severity of illness (3 M SOI) subclasses. METHODS: Binary logistic and zero-truncated negative binomial regression models were applied to a 2-year retrospective dataset (2013-2014) with 123,641 adult inpatient admissions from a large hospital system in New York City. RESULTS: All five measures demonstrated good to strong model fit for predicting in-hospital mortality, with C-statistics of 0.74 (95% confidence interval [CI] [0.74, 0.75]), 0.80 (95% CI [0.80, 0.81]), 0.81(95% CI [0.81, 0.82]), 0.94 (95% CI [0.93, 0.94]), and 0.90 (95% CI [0.90, 0.91]) for Charlson/Deyo age-comorbidity score, V W Elixhauser comorbidity score, V W Elixhauser age-comorbidity score, 3 M ROM, and 3 M SOI, respectively. The model fit statistics to predict hospital LOS measured by the likelihood ratio index were 0.3%, 1.2%, 1.1%, 6.2%, and 4.3%, respectively. DISCUSSION: The measures tested in this study can guide nurse managers in the assignment of nursing care and coordination of needed patient services and administrators to effectively and efficiently support optimal nursing care.

Impact of positive preoperative urine cultures before pediatric lower urinary tract reconstructive surgery.

PURPOSE: Children who undergo lower urinary tract reconstruction (LUTR) often have asymptomatic bacteriuria or recurrent urinary tract infections (UTI). We aimed to determine the prevalence of positive preoperative urine cultures (PPUC) before LUTR and to analyze any impact on postoperative outcomes. METHODS: This retrospective review included all pediatric LUTR procedures utilizing bowel segments performed by one surgeon over 2 years. Preoperative cultures were obtained 1-2 days before surgery. Baseline characteristics and 90-day infection/readmission rates between patients with and without PPUC were compared using descriptive statistics, Fisher's exact, and Mann-Whitney tests with significance p < 0.05. RESULTS: 54 patients with mean age 10.1 ± 5.6 years underwent LUTR procedures using bowel including continent catheterizable channel (85%), enterocystoplasty (81%), and/or urinary diversion (9%). PPUC was present in 28 patients (52%). Postoperatively, 20% had inpatient infections, including eight UTI, four surgical site infections, and two bloodstream infections with no difference between those with or without PPUC. Within 90 days of discharge, 28% of patients were readmitted to the hospital, and there was no difference between groups. Postoperative urine cultures were positive in 83% of patients within 90 days. CONCLUSIONS: Half of the patients undergoing LUTR have PPUC, but it does not increase the risk of postoperative infections or hospital readmissions. We believe complex LUTR can be safely performed in patients with PPUC.

Assessing Intensity of Nursing Care Needs Using Electronically Available Data.

Although previous research has confirmed that nurse staffing affects patient outcomes, some potentially important factors have not been accounted for in tools to assess relationships between staffing and outcomes. The aim of this project was to develop and test a Nursing Intensity of Care Index using electronically available data from 152 072 patient discharges from three hospitals. Initially, 1765 procedure codes were reviewed; 69 were confirmed as directly increasing nursing workload by at least 15 minutes per shift. Two research staff independently reviewed a random sample of 5 patient days to assess interrater reliability with complete scoring agreement. To assess face validity, eight nurse clinician experts reviewed factors included in the Nursing Intensity of Care Index to assess the accuracy of the nursing time estimates in the tool. To examine concurrent validity, Nursing Intensity of Care Index scores for a random sample of 28 patients from four clinical units were compared with assessments made by a unit-based clinical nurse (low/medium/high intensity) for the same patients on the same day with a Spearman correlation of 0.94. In preliminary testing, data for the Nursing Intensity of Care Index, which accurately reflect nursing care intensity, can be obtained electronically in real time. The next steps will be a discrete-event simulation model and large-scale field trials.

Impact of Multiplex Polymerase Chain Reaction Testing for Respiratory Pathogens on Healthcare Resource Utilization for Pediatric Inpatients.

OBJECTIVE: To assess whether multiplex polymerase chain reaction (mPCR) vs non-mPCR testing impacts the use of antibiotics, chest radiographs, and isolation precautions. STUDY DESIGN: We retrospectively compared use of antibiotics, chest radiographs, and isolation precautions for patients <18 years old (excluding neonates) hospitalized at a tertiary referral center tested for respiratory pathogens in the emergency department or during the first 2 hospital days, during 2 periods: June 2010-June 2012 (non-mPCR group) vs October 2012-May 2014 (mPCR group). RESULTS: Subjects (n = 2430) in the mPCR group were older, had more complex chronic conditions, and were admitted to the pediatric intensive care unit more often compared with the non-mPCR (n = 2349) group. Subjects in the mPCR group had more positive tests (42.4% vs 14.4%, P < .01), received fewer days of antibiotics (4 vs 5 median antibiotic days, P < .01), fewer chest radiographs performed, (59% vs 78%, P < .01), and were placed in isolation longer (20 vs 0 median isolation-hours, P < .01) compared with the non-mPCR group. In multivariable regression, patients tested with mPCR were less likely to receive antibiotics for ≥2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for ≥2 days (OR 2.4, 95% CI 2.1-2.8) compared with the non-mPCR group. CONCLUSIONS: Use of mPCR testing for respiratory viruses among hospitalized patients was significantly associated with decreased healthcare resource utilization, including decreased use of antibiotics and chest radiographs, and increased use of isolation precautions.