Association of Sex and Age with Mortality and Health-Related Quality of Life in Children with Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

Introduction: Sepsis is more common in males than females, but whether outcomes differ by sex in various pediatric age groups is unclear. The Life After Pediatric Sepsis Evaluation (LAPSE) was a multicenter prospective cohort study that evaluated health-related quality of life (HRQL) in children after community-acquired septic shock. In this secondary analysis, we evaluated whether male children are at increased risk of mortality or long-term decline in HRQL than female children by age group. Methods: Children (1 month-18 years) with community-acquired septic shock were recruited from 12 pediatric intensive care units in the U.S. Data included sex, age group (<1 year, 1-<13 years, 13-18 years), acute illness severity (acute organ dysfunction and inflammation), and longitudinal assessments of HRQL and mortality. Persistent decline in HRQL was defined as a 10% decrease in HRQL comparing baseline to 3 months following admission. Male and female children were stratified by age group and compared to evaluate the difference in the composite outcome of death or persistent decline in HRQL using the Cochran-Mantel-Haenszel test. Results: Of 389 children, 54.2% (n = 211) were male. Overall, 10% (21/211) of males and 12% (22/178) of females died by 3 months (p = 0.454). Among children with follow-up data, 41% (57/138) of males and 44% (48/108) of females died or had persistent decline in HRQL at 3 months (p = 0.636), with no observed difference by sex when stratified by age group. There was no significant difference in acute illness severity between males and females overall or stratified by age group. Conclusions: In this secondary analysis of the LAPSE cohort, HRQL, and mortality were not different between male and female children when stratified by age group. There were no significant differences by sex across multiple measures of illness severity or treatment intensity.

COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) guidelines; revisiting the Western New York approach as the pandemic evolves.

Multisystem inflammatory syndrome of children (MIS-C) continues to be a highly concerning diagnosis in those recently infected with SARS-CoV-2. The diagnosis of MIS-C cases will likely become even more challenging as vaccine uptake and natural immunity in previously infected persons leads to lower circulating rates of SARS-CoV-2 infection and will make cases sporadic. Febrile children presenting with cardiac dysfunction, symptoms overlapping Kawasaki disease or significant gastrointestinal complaints warrant a thorough screen in emergency departments, urgent care centers, and outpatient pediatric or family medicine practices. An increased index of suspicion and discussion regarding higher level of care (transferring to pediatric tertiary care centers or to intensive care) continues to be recommended. Herein we outline a broad approach with a multidisciplinary team for those meeting the case definition and believe such an approach is crucial for successful outcomes.

Bacterial and Fungal Etiology of Sepsis in Children in the United States: Reconsidering Empiric Therapy.

OBJECTIVES: Timely empiric antimicrobial therapy is associated with improved outcomes in pediatric sepsis, but minimal data exist to guide empiric therapy. We sought to describe the prevalence of four pathogens that are not part of routine empiric coverage (e.g., Staphylococcus aureus, Pseudomonas aeruginosa, Clostridium difficile, and fungal infections) in pediatric sepsis patients in a contemporary nationally representative sample. DESIGN: This was a retrospective cohort study using administrative data. SETTING: We used the Nationwide Readmissions Database from 2014, which is a nationally representative dataset that contains data from nearly half of all discharges from nonfederal hospitals in the United States. PATIENTS: Discharges of patients who were less than 19 years old at discharge and were not neonatal with a discharge diagnosis of sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 19,113 pediatric admissions with sepsis (6,300 [33%] previously healthy and 12,813 [67%] with a chronic disease), 31% received mechanical ventilation, 19% had shock, and 588 (3.1%) died during their hospitalization. Among all admissions, 8,204 (42.9%) had a bacterial or fungal pathogen identified. S. aureus was the most common pathogen identified in previously healthy patients (n = 593, 9.4%) and those with any chronic disease (n = 1,430, 11.1%). Methicillin-resistant S. aureus, P. aeruginosa, C. difficile, and fungal infections all had high prevalence in specific chronic diseases associated with frequent contact with the healthcare system, early surgery, indwelling devices, or immunosuppression. CONCLUSIONS: In this nationally representative administrative database, the most common identified pathogen was S. aureus in previously healthy and chronically ill children. In addition, a high proportion of children with sepsis and select chronic diseases had infections with methicillin-resistant S. aureus, fungal infections, Pseudomonas infections, and C. difficile. Clinicians caring for pediatric patients should consider coverage of these organisms when administering empiric antimicrobials for sepsis.

Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis.

OBJECTIVE: To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality. STUDY DESIGN: We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence, and described hospital mortality. We used mixed effects logistic regression to explore the association between chronic diseases and hospital mortality. RESULTS: A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall-0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis, oncologic, hematologic, metabolic, neurologic, cardiac and renal disease, and solid organ transplantation were associated with increased in-hospital mortality. CONCLUSIONS: More than 2 of 3 children admitted with sepsis have ≥1 chronic disease and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.

Translating biomarkers from research to clinical use in pediatric neurocritical care: focus on traumatic brain injury and cardiac arrest.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) and cardiac arrest are important causes of morbidity and mortality in children. Improved diagnosis and outcome prognostication using validated biomarkers could allow clinicians to better tailor therapies for optimal efficacy. RECENT FINDINGS: Contemporary investigation has yielded plentiful biomarker candidates of central nervous system (CNS) injury, including macromolecules, genetic, inflammatory, oxidative, and metabolic biomarkers. Biomarkers have yet to be validated and translated into bedside point-of-care or cost-effective and efficient laboratory tests. Validation testing should consider developmental status, injury mechanism, and time trajectory with patient-centered outcomes. SUMMARY: Recent investigation of biomarkers of CNS injury may soon improve diagnosis, management, and prognostication in children with traumatic brain injury and cardiac arrest.

Epidemiology of Readmissions After Sepsis Hospitalization in Children.

BACKGROUND AND OBJECTIVES: The decline in hospital mortality in children hospitalized with sepsis has increased the number of survivors. These survivors are at risk for adverse long-term outcomes, including readmission and recurrent or unresolved infections. We described the epidemiology of 90-day readmissions after sepsis hospitalization in children. We tested the hypothesis that a sepsis hospitalization increases odds of 90-day readmissions. METHODS: Retrospective cohort analysis of the Nationwide Readmissions Database. We included index unplanned admissions of non-neonatal pediatric patients and described the proportion of readmissions, including those involving infection or sepsis. We performed multivariable analysis to determine the odds of readmission after a sepsis and nonsepsis admission and compared costs of readmission after sepsis and nonsepsis admissions. RESULTS: Of 562 817 pediatric admissions, 7634 (1.4%) and 555 183 (98.6%) were discharged alive after admissions with and without sepsis. The rate of 90-day readmission after sepsis was 21.4%: 7.2% and 25.5% in previously healthy and chronically ill patients. The adjusted mean cost during readmission was $7385. Half of readmissions (52.9%) involved recurrent infection or sepsis. Sepsis admissions were associated with higher odds of readmission at 90 days compared with nonsepsis admissions (adjusted odds ratio 1.15, 95% confidence interval 1.08-1.23). The results remained unchanged for 30-day and 6-month readmissions. CONCLUSIONS: Readmissions occur after 1 in 5 pediatric sepsis hospitalizations and increase health care costs. Sepsis hospitalization increased odds of readmission and commonly involved recurrent infection or sepsis. Clinicians caring for these patients should consider surveillance for recurrent or unresolved infection, and researchers should explore underlying mechanisms and potential interventions to reduce readmissions.