Infective endocarditis with or without congenital heart disease: clinical features and outcomes.

BACKGROUND AND AIMS: Patients with congenital heart disease (CHD) form a high-risk subgroup for infective endocarditis (IE), necessitating tailored prevention and treatment strategies. However, comprehensive nationwide data comparing IE characteristics and outcomes in patients with and without CHD, including children, are sparse. This study aims to address this gap in knowledge. METHODS: Using Danish nationwide registries, all patients with IE from 1977 to 2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e. in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups. RESULTS: In total, 14 040 patients with IE were identified, including 895 (6.4%) with CHD. Patients with vs. without CHD were younger at the time of IE diagnosis (median age 38.8 vs. 70.7 years), less comorbid, and more frequently underwent cardiac surgery during admission (35.7% vs. 23.0%, P < .001). Notably, 76% of patients with IE < 18 years of age had CHD. The IE-related bacteraemia differed between groups: Streptococci (29.9%) were the most common in patients with CHD, and Staphylococcus aureus (29.9%) in patients without CHD. Patients with CHD had a significantly lower cumulative incidence of in-hospital mortality (5.7% vs. 17.0%, P < .001) and 1-year mortality (9.9% vs. 31.8%, P < .001) compared with those without CHD. The 10-year cumulative incidence of IE recurrence was similar between groups (13.0% and 13.9%, P = .61). CONCLUSIONS: Patients with CHD who develop IE exhibit distinct characteristics and improved long-term outcomes compared with patients without CHD. Notably, the majority of children and adolescents with IE have underlying CHD.

Immunogenicity and Reactogenicity of High-dose or Standard-dose Influenza Vaccine in a Second Consecutive Influenza Season.

BACKGROUND: Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. METHODS: A subcohort of study participants re-enrolled and had hemagglutinin inhibition (HAI) titers measured at baseline and four weeks after each vaccine dose in year two. We estimated geometric mean fold rise (GMFR) in HAI titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (aGMR, comparing HD-TIV to SD-QIV) for each antigen at each time point. We described systemic and injection-site reactions. RESULTS: A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Post-vaccine GMFR and aGMR estimates were higher for both groups following a single influenza vaccine dose in year two compared to two doses of the same formulation in year one. Both groups had similar frequencies of injection-site and systemic reactions. CONCLUSIONS: A single dose of HD-TIV or SD-QIV was more immunogenic in year two than two doses of the same formulation in year one. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a two-dose schedule in the prior year post-HCT.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Sex differences in infective endocarditis: a Danish nationwide study.

PURPOSE: Sex differences in infective endocarditis (IE) are reported, but patient characteristics are sparse and conflicting findings on the association between sex and short-term outcomes demand further research. We aimed to characterize sex differences in IE in terms of patient characteristics, frailty, microbiology, socioeconomic status, management and outcome on a nationwide scale. METHODS: Between 2010 and 2020, we used Danish national registries to characterize patients with IE according to sex using ICD codes and microbiological lab reports. Frailty was assessed with the Hospital Frailty Risk Score. Mortality was reported with Kaplan-Meier estimates. Logistic regression and Cox regression were used for adjusted analyses. RESULTS: We included 6259 patients with IE with 2047 (32.7%) female patients and 4212 (67.3%) male patients. Female patients were older (median age 75.0 years (64.3-82.2) vs. 71.7 (61.7-78.9)) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%). Staphylococcus aureus-IE were most common in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus-IE (10.5% vs. 18.1%). Female patients were less surgically treated (14.0% vs. 21.2%). Female sex was associated with increased in-hospital mortality (adj. OR 1.33, 95% CI 1.16-1.52), but no statistically significant difference in associated 1- and 5-year mortality from hospital discharge were identified (adj. HR 1.09, 95% CI 0.95-1.24 and 1.02, 95% CI 0.92-1.12, respectively). CONCLUSION: Female sex is associated with increased in-hospital mortality, but not in long-term mortality as compared with male patients. Female patients have a lower prevalence of Enterococcus-IE and rates of surgery. Further research is needed to understand these differences.

Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: Adult hematopoietic cell transplant (HCT) recipients are at high risk for influenza-related morbidity and mortality and have suboptimal influenza vaccine immune responses compared to healthy adults, particularly within 2 years of transplant. METHODS: This phase II, double-blind, multicenter randomized controlled trial compared 2 doses of high-dose trivalent (HD-TIV) to 2 doses of standard-dose quadrivalent (SD-QIV) influenza vaccine administered 1 month apart in adults 3-23 months post-allogeneic HCT. Hemagglutinin antibody inhibition (HAI) titers were measured at baseline, 4 weeks following each vaccine dose, and approximately 7 months post-second vaccination. Injection-site and systemic reactions were assessed for 7 days post-vaccination. The primary immunogenicity comparison was geometric mean HAI titer (GMT) at visit 3 (4 weeks after the second dose); we used linear mixed models to estimate adjusted GMT ratios (aGMRs) comparing HD-TIV/SD-QIV for each antigen. RESULTS: We randomized 124 adults; 64 received SD-QIV and 60 received HD-TIV. Following the second vaccination, HD-TIV was associated with higher GMTs compared to SD-QIV for A/H3N2 (aGMR = 2.09; 95% confidence interval [CI]: [1.19, 3.68]) and B/Victoria (aGMR = 1.61; 95% CI: [1.00, 2.58]). The increase was not statistically significant for A/H1N1 (aGMR = 1.16; 95% CI: [0.67, 2.02]). There was a trend to more injection-site reactions for HD-TIV after the second vaccination compared to SD-QIV (50% vs 33%; adjusted odds ratio [aOR] = 4.53; 95% CI: [0.71, 28.9]), whereas systemic reactions were similar between groups with both injections. CONCLUSIONS: Adult allogeneic HCT recipients who received 2 doses of HD-TIV produced higher HAI antibody responses for A/H3N2 and B/Victoria compared with 2 doses of SD-QIV, with comparable injection-site or systemic reactions.

Hemodialysis and its impact on patient characteristics, microbiology, cardiac surgery, and mortality in infective endocarditis.

BACKGROUND: Patients with chronic renal failure on hemodialysis carry a significant risk of infective endocarditis (IE), but data on whether these patients differ from other patients with IE in terms of comorbidity, microbiology, rates of surgery and mortality are sparse. METHODS: Using Danish nationwide registries, all patients with IE diagnosed between February 1, 2010, and May 14, 2018 were identified and categorized into a "hemodialysis group" and a "non-hemodialysis group." Patient groups were compared by comorbidities, microbiological etiology, cardiac surgery, and mortality. Risk factors associated with mortality were assessed in multivariable Cox regression analysis. RESULTS: In total, 4,366 patients with IE were included with 226 (5.2%) patients in the hemodialysis group. Patients in the hemodialysis group were younger (66.0 years [IQR 53.8-74.9] vs 72.2 years [IQR 62.2-80.0]), had more comorbidities and were surgically treated less often (10.6% vs 20.8%), compared with patients from the nonhemodialysis group. Staphylococcus aureus was more than twice as prevalent (58.0% vs 26.5%). No difference in in-hospital mortality was found between the 2 groups (20.8% vs 18.5%), but 1- and 5-year mortality were significantly higher in the hemodialysis group than in the nonhemodialysis group (37.7% vs 17.7% and 72.1% vs 42.5%, respectively). In adjusted analysis, hemodialysis was associated with higher 1-year (HR = 2.71, 95% CI 2.07-3.55) and 5-year mortality (HR = 2.72, 95% CI 2.22-3.34) CONCLUSIONS: Patients with IE on chronic hemodialysis were younger, had more comorbidity, a higher prevalence of Staphylococcus aureus IE, and a higher mortality than patients without hemodialysis.

[Huntington's disease with childhood and adolescent onset: course of disease, clinical presentation and diagnostic challenges]. / Zur Huntington-Erkrankung im Kindes- und Jugendalter ­ Erkrankung, klinische Präsentation und Probleme der Diagnostik.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a gene mutation in chromosome 4 that leads to an expansion of CAG - triplet repeats. It occurs mainly between the age of 30 and 50. Only less than 10 % of HD patients are younger than 20 years. In contrast to adult patients young HD patients show more often psychiatric and cognitive symptoms at disease onset than chorea. One third of the children with HD develops an epilepsy.We present 6 children diagnosed with HD in different stages of childhood. We describe first symptoms as well as genetic characteristics and other distinctive features.Both, the clinical presentation and the course of HD in childhood differ from HD in adults. In adolescents the clinical symptoms at onset are often psychiatric (like depression or attention deficit disorder). Choreatic movements typical for adult HD patients are missing.Due to the low prevalence of HD in childhood and the variability of clinical symptoms the process of diagnosing HD in children is difficult. Very often the diagnosis is made years after the first symptoms. Early diagnosis, however, is often important for managing social problems and problems in school.

YRNA expression in prostate cancer patients: diagnostic and prognostic implications.

OBJECTIVE: To study the expression of YRNAs (Ro-associated Y), a novel class of non-coding RNAs, in prostate cancer (PCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival PCA (prostate adenocarcinoma, n = 56), normal (n = 36) and benign prostatic hyperplasia (BPH; n = 28) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for biochemical recurrence-free survival were analysed. RESULTS: All YRNAs were significantly downregulated in PCA tissue compared to normal tissue (all YRNAs) and to BPH tissue (RNY4 and RNY5; RNY1 and RNY3 as trend). Among tumor ISUP grade groups, the most prominent differences in the expression were evident between groups 1 and 2 (RNY1, RNY3 und RNY4; all p < 0.05). Discrimination ability for normal/BPH tissue versus tumor tissue in ROC analysis (area under curve) was ranging from 0.658 (RNY1) to 0.739 (RNY4). Higher RNY5 expression was associated with poor prognosis (biochemical recurrence-free survival). CONCLUSION: The expression of YRNAs is altered in PCA and associated with poor prognosis (RNY5). Possible diagnostic role of YRNAs in prostate cancer should be investigated in further studies.

Longitudinal association between psychological demands and burnout for employees experiencing a high versus a low degree of job resources.

BACKGROUND: Exhaustion and burnout are common causes for sickness absence. This study examines the relationship between psychological demands and burnout over time, and if environmental support modifies the longitudinal relationship between psychological demands and burnout at baseline, with burnout measured 2 years subsequently. METHODS: A questionnaire was sent to employees in seven Swedish organizations in 2010-2012 with follow-up after 2 years, n = 1722 responded (64%). Linear regressions were used to examine the associations between burnout and psychological demands at baseline and burnout at follow-up. Stratified regression models examined if relationships between burnout and psychological demands at baseline on burnout at follow-up differed for employees in supportive versus unsupportive work environments. RESULTS: Burnout and psychological demands at baseline were associated with burnout at follow-up, after adjustment for study covariates. No significant differences were observed between estimates for psychological demands and burnout among respondents in supportive work environments versus those in unsupportive work environments. CONCLUSIONS: This study shows that high demands are associated with greater risk of burnout, regardless of level of other work supports. This has implications for prevention of sick leave due to burnout and for rehabilitation, where demands such as work pace, workload and conflicting demands at work may need to be reduced.

YRNA expression predicts survival in bladder cancer patients.

BACKGROUND: Non-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed. RESULTS: All YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients' overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma. CONCLUSIONS: The expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.

Pre-eclampsia and long-term risk of arrhythmias.

AIMS: Pre-eclampsia (PE), a pregnancy-induced hypertensive disorder, affects 4-5% of pregnancies worldwide. It is well known that hypertension is associated with an increased risk of arrhythmias; however, data on the association between PE and arrhythmias are sparse. METHODS AND RESULTS: In this observational cohort study, we identified all primiparous women who gave birth in Denmark (1997-2016) using Danish nationwide registries. The women were stratified on whether they developed PE during primiparous pregnancy and followed from primiparous pregnancy to incident arrhythmia, emigration, death, or end of study (31 December 2018). A total of 523 271 primiparous women with a median age of 28 years were included, and 23 367 (4.5%) were diagnosed with PE. During a median follow-up of 10.1 years, women with and without PE were associated with a higher incidence of arrhythmias (1.42 vs. 1.02%): (i) composite of cardiac arrest, ventricular tachycardia/fibrillation, or implantable cardioverter defibrillator implantation [adjusted hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.14-2.24], (ii) composite of advanced second- or third-degree atrioventricular block, sinoatrial dysfunction, or pacemaker implantation [adjusted HR 1.48 (95% CI 0.97-2.23)], (iii) composite of supraventricular tachyarrhythmias or extra systoles [adjusted HR 1.34 (95% CI 1.19-1.51)], and (iv) composite of all the above-mentioned arrhythmias [adjusted HR 1.37 (95% CI 1.23-1.54)]. CONCLUSION: Pre-eclamptic women were associated with a significantly and at hitherto unknown long-term increased rate of arrhythmias. This finding suggests that women with PE may benefit from cardiovascular risk assessment, screening, and preventive education.

This study examined whether pre-eclampsia (PE), a condition that can occur during pregnancy and cause high blood pressure, was linked to heart rhythm problems in first-time mothers.Women who had PE in their first pregnancy were more likely to develop heart rhythm problems later in life.This suggests that women with a history of PE might need extra attention to prevent future problems.

Bacteremia and infective endocarditis following left-sided heart valve surgery.

BACKGROUND AND AIMS: In patients undergoing heart valve surgery, subsequent bacteremia and infective endocarditis are feared events. Data on the incidence and bacterial microbiological etiology following left-sided heart valve surgery are sparse. METHODS: Between 2010-2021, all patients undergoing left-sided valve surgery were identified using Danish nationwide registries. Incidence and type bacteremia within one-year post-surgery was analyzed. Secondary outcome of interest was infective endocarditis. Cumulative incidence curves were stratified for bacterial species and for subgroups of interest: type of valve surgery, age, and sex. RESULTS: A total of 14 935 patients were included, of which 69% were male and the median age was 70.4 years (25th-75th percentile 62.4-76.2 years). The one-year cumulative incidence of bacteremia was 6.1% (95% CI 5.7-6.5%), and the most frequent bacteremia was coagulase-negative staphylococci (27%). More than half of the bacteremia with coagulase-negative staphylococci occurred within 30 days of follow-up. Patients developing bacteremia had a significantly higher Charlson comorbidity score at baseline, more often underwent CABG concomitant to valve surgery, and more often had surgery on both valves. The one-year cumulative incidence of infective endocarditis was 1.5% (95% CI 1.3-1.7), of which 23% were caused by Enterococci, and 22% were blood culture negative. The median time from surgery to infective endocarditis was 109 days. CONCLUSIONS: Bacteremia and infective endocarditis following left-sided heart valve surgery occurred in 6.1% and 1.5% of patients, respectively. The most frequent bacteremia was coagulase-negative staphylococci, and more than half of these occurred within 30 days of surgery. Optimization of prophylactic strategies are warranted.

Principal Component Patterns of Pediatric Respiratory Viral Testing Across Health Care Settings.

BACKGROUND AND OBJECTIVES: Factors prompting clinicians to request viral testing in children are unclear. We assessed patterns prompting clinicians to perform viral testing in children discharged from an emergency department (ED) or hospitalized with an acute respiratory infection (ARI). METHODS: Using active ARI surveillance data collected from November 2017 through February 2020, children aged between 30 days and 17 years with fever or respiratory symptoms who had a research respiratory specimen tested were included. Children's presentation patterns from their initial evaluation at each health care setting were analyzed using principal components (PCs) analysis. PC-specific models using logistic regression with robust sandwich estimators were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between PCs and provider-ordered viral testing. PCs were assigned respiratory virus/viruses names a priori based on the patterns represented. RESULTS: In total, 4107 children were enrolled and tested, with 2616 (64%) discharged from the ED and 1491 (36%) hospitalized. In the ED, children with a coviral presentation pattern had a 1.44-fold (95% CI, 1.24-1.68) increased odds of receiving a provider-ordered viral test than children showing clinical symptoms less representative of coviral-like infection. Whereas children in the ED and hospitalized with rhinovirus-like symptoms had 71% (OR, 0.29; 95% CI, 0.24-0.34) and 39% (OR, 0.61; 95% CI, 0.49-0.76) decreased odds, respectively, of receiving a provider-ordered viral test during their medical encounter. CONCLUSIONS: Viral tests are frequently ordered by clinicians, but presentation patterns vary by setting and influence the initiation of testing. Additional assessments of factors affecting provider decisions to use viral testing in pediatric ARI management are needed to maximize patient benefits of testing.

Clusters of emerging multidrug-resistant organisms in US health care facilities during the initial months of the SARS-CoV-2 pandemic.

BACKGROUND: Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic. METHODS: We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed. RESULTS: Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 C auris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic. CONCLUSIONS: Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

BACKGROUND: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. METHODS: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. RESULTS: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. CONCLUSION: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.

Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US.

Importance: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting. Objective: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals. Design, Setting, and Participants: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought medical care for fever and/or respiratory symptoms at 7 EDs or hospitals within NVSN across the US between December 2016 and February 2021. Persons younger than 18 years were enrolled in NVSN, and respiratory specimens were collected and tested for multiple viruses. Main Outcomes and Measures: Proportion of patients in whom rhinovirus and/or enterovirus, or another virus, was detected by calendar month and by prepandemic (December 1, 2016, to March 11, 2020) or pandemic (March 12, 2020, to February 28, 2021) periods. Month-specific adjusted odds ratios (aORs) for rhinovirus and/or enterovirus-positive test results (among all tested) by setting (ED or inpatient) and age group (<2, 2-4, or 5-17 years) were calculated, comparing each month during the pandemic to equivalent months of previous years. Results: Of the 38 198 children and adolescents who were enrolled and tested, 11 303 (29.6%; mean [SD] age, 2.8 [3.7] years; 6733 boys [59.6%]) had rhinovirus and/or enterovirus-positive test results. In prepandemic and pandemic periods, rhinoviruses and/or enteroviruses were detected in 29.4% (9795 of 33 317) and 30.9% (1508 of 4881) of all patients who were enrolled and tested and in 42.2% (9795 of 23 236) and 73.0% (1508 of 2066) of those with test positivity for any virus, respectively. Rhinoviruses and/or enteroviruses were the most frequently detected viruses in both periods and all age groups in the ED and inpatient setting. From April to September 2020 (pandemic period), rhinoviruses and/or enteroviruses were detectable at similar or lower odds than in prepandemic years, with aORs ranging from 0.08 (95% CI, 0.04-0.19) to 0.76 (95% CI, 0.55-1.05) in the ED and 0.04 (95% CI, 0.01-0.11) to 0.71 (95% CI, 0.47-1.07) in the inpatient setting. However, unlike some other viruses, rhinoviruses and/or enteroviruses soon returned to prepandemic levels and from October 2020 to February 2021 were detected at similar or higher odds than in prepandemic months in both settings, with aORs ranging from 1.47 (95% CI, 1.12-1.93) to 3.01 (95% CI, 2.30-3.94) in the ED and 1.36 (95% CI, 1.03-1.79) to 2.44 (95% CI, 1.78-3.34) in the inpatient setting, and in all age groups. Compared with prepandemic years, during the pandemic, rhinoviruses and/or enteroviruses were detected in patients who were slightly older, although most (74.5% [1124 of 1508]) were younger than 5 years. Conclusions and Relevance: Results of this study show that rhinoviruses and/or enteroviruses persisted and were the most common respiratory virus group detected across all pediatric age groups and in both ED and inpatient settings. Rhinoviruses and/or enteroviruses remain a leading factor in ARI health care burden, and active ARI surveillance in children and adolescents remains critical for defining the health care burden of respiratory viruses.

Feasibility and Acceptability of an Active Video Game-Based Physical Activity Support Group (Pink Warrior) for Survivors of Breast Cancer: Randomized Controlled Pilot Trial.

BACKGROUND: Survivors of breast cancer with functional limitations have a 40% higher mortality rate than those without. Despite the known benefits of physical activity (PA), <40% of survivors of breast cancer meet the recommendations for PA. The combination of active video games (AVGs) and group-based PA counseling may hold potential for motivating PA adoption and improving physical function. However, this method has not been widely studied in survivors of breast cancer. OBJECTIVE: We aimed to determine the feasibility and acceptability of a group AVG-based multicomponent PA intervention and estimate its effect size and variability on PA and physical function in female survivors of breast cancer in a clinic setting. METHODS: Female survivors of breast cancer (N=60) were recruited through the clinic and randomly assigned to the intervention group (12 weekly sessions) or the control group (existing support group). The intervention group received game-based pedometers and participated in weekly group AVG sessions, PA behavioral coaching, and survivorship navigation discussions. A participant manual with weekly reflection worksheets was provided to reinforce the coaching lessons and promote self-led PA. The control group received conventional pedometers and participated in an existing breast cancer support group. Feasibility was assessed by enrollment rate (≥50%), retention rate (≥80%), group attendance rate (75% attending ≥9 sessions [intervention group]), and the number of technological issues and adverse events. Acceptability was measured by participants' attitudes (from strongly disagree=1 to strongly agree=5) toward the use of AVGs and the overall program. The outcomes included PA (accelerometers) and physical function (Short Physical Performance Battery and gait speed). Analysis of covariance was used to determine differences in PA and physical function between the groups. The Cohen d and its 95% CI determined the effect size and variability, respectively. All the analyses followed the intention-to-treat principle. RESULTS: Participants were an average of 57.4 (SD 10.5) years old, 70% (42/60) White, and 58% (35/60) off treatment. The enrollment rate was 55.9% (66/118). Despite substantial long-term hurricane-related disruptions, we achieved an 80% (48/60) retention. The intervention group's attendance rate was 78% (14/18), whereas the control group's attendance rate was 53% (9/17). Of the 26 game-based pedometers, 3 (12%) were damaged or lost. No study-related adverse events occurred. Acceptability items were highly rated. Steps (ß=1621.64; P=.01; d=0.72), Short Physical Performance Battery (ß=.47; P=.01; d=0.25), and gait speed (ß=.12; P=.004; d=0.48) had a significant intervention effect. CONCLUSIONS: The intervention was feasible and acceptable in this population despite the occurrence of a natural disaster. Pilot results indicate that group AVG sessions, PA coaching, and survivorship navigation produced moderate effects on PA and physical functioning. AVGs with PA counseling can potentially be used in existing breast cancer support groups to encourage PA and improve physical function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02750241; https://clinicaltrials.gov/ct2/show/NCT02750241.

Comparison of clinical presentations and burden of respiratory syncytial virus in infants across three distinct healthcare settings in Davidson County, Tennessee.

Background: The burden of respiratory syncytial virus (RSV)-associated acute respiratory illnesses among healthy infants (<1 year) in the inpatient setting is well established. The focus on RSV-associated illnesses in the outpatient (OP) and emergency department (ED) settings are however understudied. We sought to determine the spectrum of RSV illnesses in infants at three distinct healthcare settings. Methods: From 16 December 2019 through 30 April 2020, we performed an active, prospective RSV surveillance study among infants seeking medical attention from an inpatient (IP), ED, or OP clinic. Infants were eligible if they presented with fever and/or respiratory symptoms. Demographics, clinical characteristics, and illness histories were collected during parental/guardian interviews, followed by a medical chart review and illness follow-up surveys. Research nasal swabs were collected and tested for respiratory pathogens for all enrolled infants. Results: Of the 627 infants screened, 475 were confirmed eligible; 360 were enrolled and research tested. Within this final cohort, 101 (28%) were RSV-positive (IP = 37, ED = 18, and OP = 46). Of the RSV-positive infants, the median age was 4.5 months and 57% had ⩾2 healthcare encounters. The majority of RSV-positive infants were not born premature (88%) nor had underlying medical conditions (92%). RSV-positive infants, however, were more likely to have a lower respiratory tract infection than RSV-negative infants (76% vs 39%, p < 0.001). Hospitalized infants with RSV were younger, 65% required supplemental oxygen, were more likely to have lower respiratory tract symptoms, and more often had shortness of breath and rales/rhonchi than RSV-positive infants in the ED and OP setting. Conclusion: Infants with RSV illnesses seek healthcare for multiple encounters in various settings and have clinical difference across settings. Prevention measures, especially targeted toward healthy, young infants are needed to effectively reduce RSV-associated healthcare visits.

The impact of community closures among nonessential and essential workers, Nashville, Tennessee: A cross-sectional study.

Background and Aims: The effects of community closures and relaxing social distancing restrictions on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by occupational risk remain unclear. Therefore, we evaluated the impact of community closures and reopening phases with the prevalence of testing SARS-CoV-2-positive among nonessential and essential workers. Methods: We constructed a cross-sectional cohort from March 20 to July 31, 2020, of 344 adults from Metropolitan Nashville, Tennessee. We performed an unconditional logistic regression model to evaluate the impact of community closures and phase implementation on testing SARS-CoV-2 positive by occupation to estimate adjusted prevalence odds ratios (aPORs) and 95% confidence intervals (CIs). Results: During a stay-at-home/Phase I order, those with non-essential occupations had 59% decreased prevalence odds (aPOR:0.41; 95% CI: 0.20-0.84) of testing SARS-CoV-2-positive compared to when no restrictions were in place. Persons with essential occupations had four times the prevalence odds of testing SARS-CoV-2-positive (aPOR:4.19; 95% CI:1.57-11.18) compared with nonessential occupations when no community restrictions were established. Conclusion: Stay-at-home restrictions were associated with a lower risk of SARS-CoV-2 infection in the community for nonessential workers. Essential employees remained at increased risk for SARS-CoV-2, including when no community restrictions were in place and vaccines were not available. This study supports targeting prevention measures for these high-risk occupations.