Development and Initial Psychometric Validation of the COVID-19 Pandemic Burden Index for Healthcare Workers.

BACKGROUND: The burden of COVID-19 on healthcare workers (HCWs) is reported to be increasing, yet the psychometric scales now in use evaluate only single aspects; few measure the pandemic-specific burden on HCWs comprehensively. OBJECTIVE: To develop a scale to quantify the physical, mental, and socioeconomic burden of the COVID-19 pandemic on HCWs. DESIGN: Scale development and cross-sectional survey. PARTICIPANTS: Consenting HCWs aged ≥20. MAIN MEASURES: Development of an item-list based on literature reviews and HCW panel input, evaluation of content validity and item selection using the Delphi method, psychometric testing conducted on HCWs, validity assessment by factor analyses and hypothesis verification, internal consistency evaluation by Cronbach's alpha, test-retest analysis, and interpretability assessment. KEY RESULTS: Through the Delphi process, a 29-item pilot scale was generated. In psychometric testing, data from 863 HCWs contributed to the development of the final version of this scale, called Pandemic Burden Index twenty for HCWs (PBI-20), a 20-item scale to measure six domains: fatigue, fear of infection, inadequacy as a medical professional, mental health concerns, prejudice or discrimination, and anxiety about one's livelihood and daily life. Factor analysis showed each factor corresponded to the six domains of this scale. Hypothesis verification showed the PBI-20 total score to be moderately to highly correlated with the Short Form 36 vitality score and mental health score and with intention of turnover. The PBI-20 had good internal consistency (Cronbach's alpha 0.92). Test-retest analysis showed the intraclass correlation coefficient to be 0.70 and the minimal important change to be -7.0. CONCLUSIONS: The psychometrically sound questionnaire we developed to measure pandemic-specific burdens for HCWs provides an understanding of comprehensive burdens on HCWs and may serve to evaluate interventions to reduce the burdens.

Plasma metabolomics identifies differing endotypes of recurrent wheezing in preschool children differentiated by symptoms and social disadvantage.

Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing. K-means cluster analysis was performed on metabolomic dataset including a total of 1382 named and unnamed metabolites. We identified three metabolomic clusters which differed in symptom severity, exacerbation occurrence, and variables associated with social disadvantage. Metabolites that distinguished the clusters included those involved in fatty acid metabolism, fatty acids (long chain monounsaturated fatty acids, long chain polyunsaturated fatty acids, and long chain saturated fatty acids), lysophospholipids, phosphatidylcholines, and phosphatidylethanolamines. Pathway analyses identified pathways of interest in each cluster, including steroid metabolism, histidine metabolism, sphingomyelins, and sphingosines, among others. This study highlights the biologic complexity of recurrent wheezing in preschool children and offers novel metabolites and pathways that may be amenable to future study and intervention.

Association between comorbidities at ICU admission and post-Sepsis physical impairment: A retrospective cohort study.

PURPOSE: Few studies have measured the association between pre-existing comorbidities and post-sepsis physical impairment. The study aimed to estimate the risk of physical impairment at hospital discharge among sepsis patients, adjusting for pre-existing physical impairment prior to ICU admission and in-hospital mortality. MATERIALS AND METHODS: We analyzed all consecutive adult patients admitted to an ICU in a tertiary community hospital, Kameda Medical Center, with sepsis diagnosis from September 2014 to October 2020. Inverse probability attrition weighting using machine learning was employed to estimate the risk of physical impairment at hospital discharge for sepsis patients with and without pre-existing comorbidities at ICU admission. This estimation was adjusted for baseline covariates, pre-ICU physical impairment, and in-hospital mortality. RESULTS: Of 889 sepsis patients analyzed, 668 [75.1%] had at least one comorbidity and 221 [24.9%] had no comorbidities at ICU admission. Upon adjusting for baseline covariates, pre-ICU physical impairment, and in-hospital mortality, pre-existing comorbidities were not associated with an elevated risk of physical impairment at hospital discharge (RR: 1.02, 95% CI: 0.92, 1.14). CONCLUSIONS: Pre-existing comorbidities prior to ICU admission were not associated with an increased risk of physical impairment at hospital discharge among sepsis patients after adjusting for baseline covariates and in-hospital mortality.

Metabolomics identifies disturbances in arginine, phenylalanine, and glycine metabolism as differentiating features of exacerbating atopic asthma in children.

Background: Asthma exacerbations are highly prevalent in children, but only a few studies have examined the biologic mechanisms underlying exacerbations in this population. Objective: High-resolution metabolomics analyses were performed to understand the differences in metabolites in children with exacerbating asthma who were hospitalized in a pediatric intensive care unit for status asthmaticus. We hypothesized that compared with a similar population of stable outpatients with asthma, children with exacerbating asthma would have differing metabolite abundance patterns with distinct clustering profiles. Methods: A total of 98 children aged 6 through 17 years with exacerbating asthma (n = 69) and stable asthma (n = 29) underwent clinical characterization procedures and submitted plasma samples for metabolomic analyses. High-confidence metabolites were retained and utilized for pathway enrichment analyses to identify the most relevant metabolic pathways that discriminated between groups. Results: In all, 118 and 131 high-confidence metabolites were identified in positive and negative ionization mode, respectively. A total of 103 unique metabolites differed significantly between children with exacerbating asthma and children with stable asthma. In all, 8 significantly enriched pathways that were largely associated with alterations in arginine, phenylalanine, and glycine metabolism were identified. However, other metabolites and pathways of interest were also identified. Conclusion: Metabolomic analyses identified multiple perturbed metabolites and pathways that discriminated children with exacerbating asthma who were hospitalized for status asthmaticus. These results highlight the complex biology of inflammation in children with exacerbating asthma and argue for additional studies of the metabolic determinants of asthma exacerbations in children because many of the identified metabolites of interest may be amenable to targeted interventions.

Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report.

To investigate the relationship between ICU-acquired weakness (ICUAW) signatures and sepsis-related mortality using gene expression from the blood within 24 hours of sepsis onset. DESIGN: Observational study using differential gene expression analysis. SETTING: Publicly available gene expression profile GSE54514, single-center medical and surgical ICU. PATIENTS: Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were 18 years old and older and admitted to ICU. MEASUREMENTS AND MAIN RESULTS: Among validated 526 ICUAW gene signatures, differential gene expression analysis controlling for age identified 38 significantly expressed genes between nonsurvivors and survivors. Functional enrichment analysis of differentially expressed ICUAW genes identified impaired cadherin binding, sarcomere formation, and energy metabolism among nonsurvivors. CONCLUSIONS: Our findings demonstrated a biological association between sepsis-related mortality and ICUAW signatures in the early phase of sepsis. Defects in energy metabolism and muscle fiber formation were associated with sepsis-related mortality.

Relationship between community walking ability and in-hospital mortality in elderly patients with sepsis: a single-center retrospective cohort study.

PURPOSE: To examine the association of a simple frailty assessment, Life Space (LS), with in-hospital mortality in elderly patients with sepsis. METHODS: We used data from a single hospital between 2014 and 2017. We included elderly patients (age ≥ 65 years) admitted to the intensive care unit (ICU) with sepsis, as defined by sepsis-3 criteria. Frailty assessment was based on a patient's ability to independently go out of the house before the ICU admission. We termed this dichotomous score as Life Space. The primary outcome was in-hospital mortality. Logistic regression was used to investigate the association of LS with each outcome after adjusting for age, sex, and Sequential Organ Failure Assessment score. RESULTS: Of the 335 participants included in the final analysis, 121 (36%) were classified as frail. LS-positive patients had a higher in-hospital mortality (adjusted odds ratio (aOR) 2.32; 95% confidence interval (CI) 1.36-3.96; P = 0.002) than did LS-negative patients. We observed similar patterns in six sets of sensitivity analyses after accounting for different confounders. In subgroup analyses, significant interactions were observed in participants with versus those without treatment limitations (aOR 1.02 vs. 2.66, P for interaction = 0.042). CONCLUSIONS: In this single-center study, frailty assessed by LS was independently associated with a higher in-hospital mortality.