Accuracy and Interpretation of Transcutaneous Carbon Dioxide Monitoring in Critically Ill Children.

OBJECTIVES: Transcutaneous carbon dioxide (Tc co2 ) monitoring can noninvasively assess ventilation by estimating carbon dioxide ( CO2 ) levels in the blood. We aimed to evaluate the accuracy of Tc co2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Pa co2 ). In addition, we sought to determine the variation between Tc co2 and Pa co2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tc co2 measurements. DESIGN: Retrospective observational cohort study. SETTING: Single, quaternary care PICU from July 1, 2012, to August 1, 2020. PATIENTS: Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tc co2 measurements obtained within 15 minutes of Pa co2 measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three thousand four hundred seven paired arterial blood gas and Tc co2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tc co2 levels against Pa co2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tc co2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tc co2 with Pa co2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tc co2 accuracy. CONCLUSIONS: Tc co2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.

Real-life effectiveness and safety of baricitinib in patients with severe alopecia areata: A 24-week Italian study.

BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows and eyelashes, for which treatments are limited. Baricitinib, an oral inhibitor of Janus kinases 1 and 2, has been recently approved to treat alopecia areata. MATERIALS AND METHODS: We conducted a retrospective study involving 23 medical centres across Italy, enrolling patients affected by severe alopecia areata (SALT >50), for more than 6 months. Clinical and trichoscopic assessment was performed at each visit and impact on quality of life, anxiety and depression were evaluated using the Skindex-16 and the Hospital Anxiety and Depression Scale (HADS), respectively. RESULTS: A total of 118 patients were enrolled, with a mean age of 39 years and a mean SALT >95. The mean value of the SALT score decreased from an average of 96.6 (±8.23 sd) to 48 (±35.2 sd) after 24 weeks of treatment and 42.3% of patients achieved a SALT 30, 31.3% a SALT 20 and 20.3% a SALT 10 by Week 24. Trichoscopic signs showed fewer yellow dots and black dots significantly earlier than hair regrowth. Adverse events during the treatment period (mild laboratory test abnormalities) were reported in 12.7% patients. No drop-out were registered. CONCLUSION: Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early stages. We also suggest performing trichoscopy in order to reveal early response to therapy.

The level of dental fear and anxiety is higher in children with both severe Molar-Incisor Hypomineralisation and active dental caries lesions compared to children without these conditions.

PURPOSE: To assess levels of dental fear and anxiety (DFA) in children with and without Molar-Incisor Hypomineralisation (MIH) and dental caries lesions. METHODS: In this cross-sectional observational study, 159 children between 8 and 12 years of age were included. For the evaluation of DFA, children responded to the validated version of the Children's Fear Survey Schedule-Dental Subscale. MIH was assessed using the MIH Index. To evaluate the activity of dental caries lesions and dental caries experience, the Nyvad criterion and the dmft/DMFT index were used, respectively. Dental hypersensitivity was evaluated using air stimulation and a Visual Analogue Scale. The association between MIH and dental caries with DFA was assessed using the generalised linear model with Poisson family, identity link function and robust variance estimation. The significance level was set at 5%. RESULTS: The mean DFA score was 28.3 (SD = 13.4) with scores ranging from 15 to 64. Amongst children presenting both MIH and dental caries, the perception of DFA was notably higher compared to those with either MIH or dental caries alone. The activity of caries lesion in patients with MIH also influenced DFA levels (diff: 18.6; 95% CI: 12.0-25.2; p < 0.001). Dental caries experience in the primary dentition also demonstrated statistical significance concerning DFA (95% CI: 0.8-13.3; p value = 0.027). CONCLUSION: Children with MIH exhibit higher levels of DFA than children without MIH. The experience of dental caries and the activity of caries lesions significantly influence the perception of DFA in children with MIH.

A matched analysis of the use of high flow nasal cannula for pediatric severe acute asthma.

RATIONALE: The high-flow nasal cannula (HFNC) device is commonly used to treat pediatric severe acute asthma. However, there is little evidence regarding its effectiveness in real-world practice. OBJECTIVES: We sought to compare the physiologic effects and clinical outcomes for children treated for severe acute asthma with HFNC versus matched controls. METHODS: This was a single-center retrospective matched cohort study at a quaternary care children's hospital. Children ages 2-18 hospitalized for severe acute asthma from 2015 to 2022 were included. Encounters receiving treatment with HFNC within the first 24 h of hospitalization were included as cases. Controls were primarily treated with oxygen facemask. Logistic regression 1:1 propensity score matching was done using demographics, initial vital signs, and medications. The primary outcome was an improvement in clinical asthma symptoms in the first 24 h of hospitalization measured as percent change from initial. MEASUREMENTS AND MAIN RESULTS: Of 693 eligible cases, 443 were matched to eligible controls. Propensity scores were closely aligned between the cohorts, with the only significant difference in clinical characteristics being a higher percentage of patients of Black race in the control group (54.3% vs. 46.6%; p = 0.02). Compared to the matched controls, the HFNC cohort had smaller improvements in heart rate (-11.5% [-20.9; -0.9] vs. -14.7% [-22.6;-5.7]; p < 0.01), respiratory rate (-14.3% [-27.9;5.4] vs. -16.7% [-31.5;0.0]; p = 0.03), and pediatric asthma severity score (-14.3% [-28.6;0.0] vs. -20.0% [-33.3;0.0]; p < 0.01) after 24 h of hospitalization. The HFNC cohort also had longer pediatric intensive care unit (PICU) length of stay (LOS) (1.5 days [1.1;2.1] vs. 1.2 days [0.9;1.8]; p < 0.01) and hospital LOS (2.8 days [2.1;3.8] vs. 2.5 days [1.9;3.4]; p < 0.01). When subgrouping to younger patients (2-3 years old), or those with the highest severity scores (PASS > 9), those treated with HFNC had no difference in clinical symptom improvements but maintained a longer PICU LOS. CONCLUSIONS: Encounters using HFNC for severe acute pediatric asthma had decreased clinical improvement in 24 h of hospitalization compared to matched controls and increased LOS. Specific subgroups of younger patients and those with the highest severity scores showed no differences in clinical symptom improvement suggesting differential effects in specific patient populations.

Digital solutions in paediatric sepsis: current state, challenges, and opportunities to improve care around the world.

The digitisation of health care is offering the promise of transforming the management of paediatric sepsis, which is a major source of morbidity and mortality in children worldwide. Digital technology is already making an impact in paediatric sepsis, but is almost exclusively benefiting patients in high-resource health-care settings. However, digital tools can be highly scalable and cost-effective, and-with the right planning-have the potential to reduce global health disparities. Novel digital solutions, from wearable devices and mobile apps, to electronic health record-embedded decision support tools, have an unprecedented opportunity to transform paediatric sepsis research and care. In this Series paper, we describe the current state of digital solutions in paediatric sepsis around the world, the advances in digital technology that are enabling the development of novel applications, and the potential effect of advances in artificial intelligence in paediatric sepsis research and clinical care.

Identification of severe acute pediatric asthma phenotypes using unsupervised machine learning.

RATIONALE: More targeted management of severe acute pediatric asthma could improve clinical outcomes. OBJECTIVES: To identify distinct clinical phenotypes of severe acute pediatric asthma using variables obtained in the first 12 h of hospitalization. METHODS: We conducted a retrospective cohort study in a quaternary care children's hospital from 2014 to 2022. Encounters for children ages 2-18 years admitted to the hospital for asthma were included. We used consensus k means clustering with patient demographics, vital signs, diagnostics, and laboratory data obtained in the first 12 h of hospitalization. MEASUREMENTS AND MAIN RESULTS: The study population included 683 encounters divided into derivation (80%) and validation (20%) sets, and two distinct clusters were identified. Compared to Cluster 1 in the derivation set, Cluster 2 encounters (177 [32%]) were older (11 years [8; 14] vs. 5 years [3; 8]; p < .01) and more commonly males (63% vs. 53%; p = .03) of Black race (51% vs. 40%; p = .03) with non-Hispanic ethnicity (96% vs. 84%; p < .01). Cluster 2 encounters had smaller improvements in vital signs at 12-h including percent change in heart rate (-1.7 [-11.7; 12.7] vs. -7.8 [-18.5; 1.7]; p < .01), and respiratory rate (0.0 [-20.0; 22.2] vs. -11.4 [-27.3; 9.0]; p < .01). Encounters in Cluster 2 had lower percentages of neutrophils (70.0 [55.0; 83.0] vs. 85.0 [77.0; 90.0]; p < .01) and higher percentages of lymphocytes (17.0 [8.0; 32.0] vs. 9.0 [5.3; 14.0]; p < .01). Cluster 2 encounters had higher rates of invasive mechanical ventilation (23% vs. 5%; p < .01), longer hospital length of stay (4.5 [2.6; 8.8] vs. 2.9 [2.0; 4.3]; p < .01), and a higher mortality rate (7.3% vs. 0.0%; p < .01). The predicted cluster assignments in the validation set shared the same ratio (~2:1), and many of the same characteristics. CONCLUSIONS: We identified two clinical phenotypes of severe acute pediatric asthma which exhibited distinct clinical features and outcomes.

Identification and transcriptomic assessment of latent profile pediatric septic shock phenotypes.

BACKGROUND: Sepsis poses a grave threat, especially among children, but treatments are limited owing to heterogeneity among patients. We sought to test the clinical and biological relevance of pediatric septic shock subclasses identified using reproducible approaches. METHODS: We performed latent profile analyses using clinical, laboratory, and biomarker data from a prospective multi-center pediatric septic shock observational cohort to derive phenotypes and trained a support vector machine model to assign phenotypes in an internal validation set. We established the clinical relevance of phenotypes and tested for their interaction with common sepsis treatments on patient outcomes. We conducted transcriptomic analyses to delineate phenotype-specific biology and inferred underlying cell subpopulations. Finally, we compared whether latent profile phenotypes overlapped with established gene-expression endotypes and compared survival among patients based on an integrated subclassification scheme. RESULTS: Among 1071 pediatric septic shock patients requiring vasoactive support on day 1 included, we identified two phenotypes which we designated as Phenotype 1 (19.5%) and Phenotype 2 (80.5%). Membership in Phenotype 1 was associated with ~ fourfold adjusted odds of complicated course relative to Phenotype 2. Patients belonging to Phenotype 1 were characterized by relatively higher Angiopoietin-2/Tie-2 ratio, Angiopoietin-2, soluble thrombomodulin (sTM), interleukin 8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1) and lower Tie-2 and Angiopoietin-1 concentrations compared to Phenotype 2. We did not identify significant interactions between phenotypes, common treatments, and clinical outcomes. Transcriptomic analysis revealed overexpression of genes implicated in the innate immune response and driven primarily by developing neutrophils among patients designated as Phenotype 1. There was no statistically significant overlap between established gene-expression endotypes, reflective of the host adaptive response, and the newly derived phenotypes, reflective of the host innate response including microvascular endothelial dysfunction. However, an integrated subclassification scheme demonstrated varying survival probabilities when comparing patient endophenotypes. CONCLUSIONS: Our research underscores the reproducibility of latent profile analyses to identify pediatric septic shock phenotypes with high prognostic relevance. Pending validation, an integrated subclassification scheme, reflective of the different facets of the host response, holds promise to inform targeted intervention among those critically ill.

phoenix: an R package and Python module for calculating the Phoenix pediatric sepsis score and criteria.

Objectives: The publication of the Phoenix criteria for pediatric sepsis and septic shock initiates a new era in clinical care and research of pediatric sepsis. Tools to consistently and accurately apply the Phoenix criteria to electronic health records (EHRs) is one part of building a robust and internally consistent body of research across multiple research groups and datasets. Materials and Methods: We developed the phoenix R package and Python module to provide researchers with intuitive and simple functions to apply the Phoenix criteria to EHR data. Results: The phoenix R package and Python module enable researchers to apply the Phoenix criteria to EHR datasets and derive the relevant indicators, total scores, and sub-scores. Discussion: The transition to the Phoenix criteria marks a major change in the conceptual definition of pediatric sepsis. Applicable across differentially resourced settings, the Phoenix criteria should help improve clinical care and research. Conclusion: The phoenix R package and Python model are freely available on CRAN, PyPi, and GitHub. These tools enable the consistent and accurate application of the Phoenix criteria to EHR datasets.

Accuracy and Interpretation of Transcutaneous Carbon Dioxide Monitoring in Critically Ill Children.

OBJECTIVES: Transcutaneous carbon dioxide (Tcco2) monitoring can noninvasively assess ventilation by estimating carbon dioxide (CO2) levels in the blood. We aimed to evaluate the accuracy of Tcco2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Paco2). In addition, we sought to determine the variation between Tcco2 and Paco2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tcco2 measurements. DESIGN: Retrospective observational cohort study. SETTING: Single, quaternary care PICU from July 1, 2012, to August 1, 2020. PATIENTS: Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tcco2 measurements obtained within 15 minutes of Paco2 measurement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three thousand four hundred seven paired arterial blood gas and Tcco2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tcco2 levels against Paco2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tcco2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tcco2 with Paco2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tcco2 accuracy. CONCLUSIONS: Tcco2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.

Medical Complexity, Language Use, and Outcomes in the Pediatric ICU.

OBJECTIVES: To determine whether use of a language other than English (LOE) would be associated with medical complexity, and whether medical complexity and LOE together would be associated with worse clinical outcomes. METHODS: The primary outcome of this single-site retrospective cohort study of PICU encounters from September 1, 2017, through August 31, 2022 was an association between LOE and medical complexity. Univariable and multivariable analyses were performed between demographic factors and medical complexity, both for unique patients and for all encounters. We investigated outcomes of initial illness severity (using Pediatric Logistic Organ Dysfunction-2), length of stay (LOS), days without mechanical ventilation or organ dysfunction using a mixed effects regression model, controlling for age, sex, race and ethnicity, and insurance status. RESULTS: There were 6802 patients and 10 011 encounters. In multivariable analysis for all encounters, Spanish use (adjusted odds ratio [aOR], 1.29; 95% confidence interval [CI], 1.11-1.49) and language other than English or Spanish (LOES) (aOR, 1.36; 95% CI, 1.02-1.80) were associated with medical complexity. Among unique patients, there remained an association between use of Spanish and medical complexity in multivariable analysis (aOR, 1.26; 95% CI, 1.05-1.52) but not between LOES and medical complexity (aOR, 1.30; 95% CI, 0.92-1.83). Children with medical complexity (CMC) who used an LOES had fewer organ dysfunction-free days (P = .003), PICU LOS was 1.53 times longer (P = .01), and hospital LOS was 1.45 times longer (P = .01) compared with CMC who used English. CONCLUSIONS: Use of an LOE was independently associated with medical complexity. CMC who used an LOES had a longer LOS.