The Use of Botulinum Toxin Type A in Medically Refractory Pediatric Patients With Chronic Daily Headaches and Its Impact on the Quality of Life.

Background: Chronic migraine in children has been a challenging condition to treat, prompting the investigation of alternative therapies. This retrospective single-center chart review aimed to evaluate the efficacy and safety of Botox injections for managing chronic migraine in children. Methods: The study included children with chronic daily headaches and chronic migraine who were medically refractory to previous treatments at OSF Healthcare/Illinois Neurological Institute, Peoria, between 2015 and 2021. Botox injections were administered quarterly following a specific protocol. Data were obtained from electronic medical records by manual review. Results: Twenty-four patients met the inclusion criteria (median age 15.4 years, 87% female). Comorbidities included depression (41.6%) and sleep disturbances (33.2%). Prior to Botox treatment, patients had been tried on a median number of 5 (interquartile range [IQR] 4, 7) medications. Botox injections resulted in a significant reduction in headache frequency, with a mean difference (6 months vs pretreatment) in the Headache Impact Test (HIT 3) scores of -19.6 (95% CI -24.8, -14.3), P < .001, and mean difference in the Migraine Disability Assessment (MIDAS) scores of -50.8 (95% CI -62.6, -39.0, P < .001). Subjective improvements included mood enhancement (13/24, 54.2%) and improved concentration (12/24, 50%). Treatment-related side effects were reported by 5/24 (20%) of patients and were mostly mild to moderate. Conclusions: Botox injections offer a promising therapeutic option for managing chronic migraine in children who have not responded to traditional medications. Future controlled trials and long-term follow-up studies are needed to further evaluate Botox treatment's benefits and adverse effects in children with chronic migraine.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Poke Plan: An Initiative to Improve Distraction and Pain Mitigation With Venous Access in Hospitalized Children.

BACKGROUND: Adequate pain control and anxiety relief during peripheral intravenous cannula (PIV) placement improves patient, parental, and staff satisfaction and reduces health care-induced stress in children. We noted a low rate of analgesic/anxiolysis use (<20%) and child life utilization (3%) in our institution. This quality improvement project was initiated to increase pain mitigation strategies in hospitalized children requiring PIV access. METHODS: From November 2020 to March 2021, we created a key driver diagram and summarized possible interventions with the aim to increase our use of pain control strategies to >40% and child life utilization to 25%. For 12 months, 8 Plan-Do-Study-Act cycles were conducted focusing on nursing education and training, improved documentation, electronic medical record optimization, easy access to analgesics and anxiolytics, family involvement, and weekly huddles. Our primary measure was the percentage use of pain medications for PIV access. The utilization of PIV experts from the ICU (advanced practice registered nurses and physicians) served as the balancing measure. RESULTS: A total of 883 patient charts were reviewed. The use of topical anesthetics and anxiolytics increased from 16.2% at baseline to 78.9% after the implementation of the quality improvement project. Eighty percent of parents reported their child was kept comfortable during the procedure using pain mitigation and comfort measures. A slight increase from 2% to 5.8% was noted in the utilization of advanced practice registered nurses and intensivists. CONCLUSIONS: Implementation of a standardized approach for PIV placement improved team communication and provided better preparation for pain control before needle insertions in hospitalized children.

Description and Validation of a Novel Score (Flow Index) as a Clinical Indicator of the Level of Respiratory Support to Children on High Flow Nasal Cannula.

This study's objective was to describe and validate flow index (flow rate × FiO 2 /weight) as a method to report the degree of respiratory support by high flow nasal cannula (HFNC) in children. We conducted a retrospective chart review of children managed with HFNC from January 1, 2015 to December 31, 2019. Variables included in the flow index (weight, fraction of inspired oxygen [FiO 2 ], flow rate) and outcomes (hospital and intensive care unit [ICU] length of stay [LOS], escalation to the ICU) were extracted from medical records. Max flow index was defined by the earliest timestamp when patients FiO 2 × flow rate was maximum. Step-wise regression was used to determine the relationship between outcome (LOS and escalation to ICU) and flow index. Fifteen hundred thirty-seven patients met the study criteria. The median first and maximum flow indexes of the population were 24.1 and 38.1. Both first and maximum flow indexes showed a significant correlation with the LOS ( r = 0.25 and 0.31, p < 0.001). Correlation for the index was stronger than that of the variables used to calculate them and remained significant after controlling for age, race, sex, and diagnoses. Mild, moderate, and severe categories of first and max flow index were derived using quartiles, and they showed significant age and diagnosis independent association with LOS. Patients with first flow index >20 and maximum flow index >59.5 had increased odds ratio of escalation to ICU (odds ratio: 2.39 and 8.08). The first flow index had a negative association with rapid response activation. Flow index is a valid measure for assessing the degree of respiratory support for children on HFNC.

Compliance With Central Line Maintenance Bundle and Infection Rates.

BACKGROUND: Reliable bundle performance is the mainstay of central line-associated bloodstream infections (CLABSI) prevention despite an unclear relationship between bundle reliability and outcomes. Our primary objective was to evaluate the correlation between reported bundle compliance and CLABSI rate in the Solutions for Patient Safety network. The secondary objective was to identify which hospital and process factors impact this correlation. METHODS: We examined data on bundle compliance and monthly CLABSI rates from January 11 to December 21 in 159 hospitals. The correlation (adjusting for temporal trend) between CLABSI rates and bundle compliance was done at the network level. Negative binomial regression was done to detect the impact of hospital type, central line audit rate, and adoption of a comprehensive safety culture program on the association between bundle compliance and CLABSI rates. RESULTS: During the study, hospitals reported 27 196 CLABSI on 20 274 565 line days (1.34 CLABSI/1000 line days). Out of 2 460 133 observed bundle opportunities, 2 085 700 (84%) were compliant. There was a negative correlation between the monthly bundle reliability and monthly CLABSI rate (-0.35, P <.001). After adjusting for the temporal trend, the partial correlation was -0.25 (P = .004). On negative binomial regression, significant positive interaction was only noted for the hospital type, with Hospital Within Hospital (but not freestanding children's hospitals) revealing a significant association between compliance ≥95% and lower CLABSI rates. CONCLUSIONS: Adherence to best practice guidelines is associated with a reduction in CLABSI rate. Hospital-level factors (hospitals within hospitals vs freestanding), but not process-related (central line audit rate and safety culture training), impact this association.

A cost-effectiveness analysis of ruxolitinib versus best alternative therapy for patients with steroid-refractory chronic graft-versus-host disease aged > 12 years in Singapore.

BACKGROUND: Approximately 30-70% of patients who have undergone allogeneic (allo) hematopoietic stem cell transplantation (HSCT) eventually experience chronic graft-versus-host disease (cGVHD). Patients who develop steroid-refractory (SR)-cGVHD are the most severely impacted due to significant disease and financial burden. There remains an unmet need for safe, efficacious, and accessible treatments for these patients. The objective of this study was to determine the cost effectiveness of ruxolitinib for treatment of SR-cGvHD from the Singapore healthcare system perspective. METHODS: Based on data from the REACH3 randomized open-label trial, a semi-Markov model was developed to evaluate cost-effectiveness of ruxolitinib compared with investigators' choice of best alternative therapy (BAT) for treatment of patients > 12 years of age with SR-cGVHD in Singapore over a 40-year time horizon. The model only considered direct medical-care costs related to the treatment of SR-cGVHD and reported them in Singapore Dollars (SGD). Half-cycle correction was applied to all costs and outcomes, which were discounted at 3%. Probabilistic sensitivity analysis (PSA), one-way sensitivity analysis (OWSA), and scenario analysis were conducted to explore the drivers of uncertainty in the model. RESULTS: In the deterministic base case, more life years (LY; 10.28 vs. 9.42) and quality-adjusted life years (QALYs; 7.31 vs. 6.51) were gained with ruxolitinib than BAT at higher costs (SGD 303,214 vs. SGD 302,673) leading to an incremental cost-effectiveness ratio (ICER) of SGD 677/QALY. At a willingness-to-pay threshold of SGD 75,000/QALY gained, PSA found that ruxolitinib had a 78.52% probability of being cost-effective. Findings were sensitive to variations in non-responder utilities in the BAT arm and duration of BAT treatment in the OWSA, or comparison to either methotrexate (MTX) or mycophenolic acid as a single comparator in the scenario analysis. ICERs remained lower than SGD 75,000/QALY in all other tested variations and scenarios. CONCLUSION: Ruxolitinib is likely to be cost-effective from Singapore healthcare system's perspective for patients with SR-cGVHD, which is promising in the management of patients with unmet clinical needs.

Analgesia and Sedation at Terminal Extubation: A Secondary Analysis From Death One Hour After Terminal Extubation Study Data.

OBJECTIVES: To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD). DESIGN: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. SETTING: Nine U.S. hospitals. PATIENTS: Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021). MEASUREMENTS AND MAIN RESULTS: Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/F io2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) ( n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) ( n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. CONCLUSIONS: Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

Quality of life with ribociclib versus abemaciclib as first-line treatment of HR+/HER2- advanced breast cancer: a matching-adjusted indirect comparison.

Background: A cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy is recommended as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Quality of life (QoL) is an important endpoint that affects treatment decisions. Understanding the relevance of CDK4/6i treatment on QoL is gaining importance given use in earlier treatment lines for ABC and an emerging role in treating early breast cancer in which QoL may be more impactful. In the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) permits comparative efficacy between trials. Objective: In this analysis, patient-reported QoL for MONALEESA-2 [ribociclib + aromatase inhibitor (AI)] and MONARCH 3 (abemaciclib + AI) was compared using MAIC with a focus on individual domains. Design: An anchored MAIC of QoL comparing ribociclib + AI versus abemaciclib + AI was performed using data from the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ)-C30 and BR-23 questionnaires. Methods: Individual patient data from MONALEESA-2 and published aggregated data from MONARCH 3 were included in this analysis. Time to sustained deterioration (TTSD) was calculated as the time from randomization to a ⩾10-point deterioration with no later improvement above this threshold. Results: Patients from the ribociclib (n = 205) and placebo (n = 149) arms of MONALEESA-2 were matched with patients from the abemaciclib (n = 328) and placebo (n = 165) arms of MONARCH 3. After weighting, baseline patient characteristics were well balanced. TTSD significantly favored ribociclib versus abemaciclib in appetite loss [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.27-0.81], diarrhea (HR, 0.42; 95% CI, 0.23-0.79), fatigue (HR, 0.63; 95% CI, 0.41-0.96), and arm symptoms (HR, 0.49; 95% CI, 0.30-0.79). TTSD did not significantly favor abemaciclib compared with ribociclib in any functional or symptom scale of the QLQ-C30 or BR-23 questionnaires. Conclusions: This MAIC indicates that ribociclib + AI is associated with better symptom-related QoL than abemaciclib + AI for postmenopausal patients with HR+/HER2- ABC treated in the first-line setting. Trial registration: NCT01958021 (MONALEESA-2) and NCT02246621 (MONARCH 3).

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Epidemiology and Outcomes of Bacterial Coinfection in Hospitalized Children With Respiratory Viral Infections: A Single Center Retrospective Chart Review.

OBJECTIVE: Children with viral respiratory illness are often suspected of having bacterial coinfection. This study was designed to determine the impact of bacterial coinfection on hospital course and outcomes and the rate of antimicrobial misuse. METHODS: Single-center retrospective chart review, including all hospitalized children who had a respiratory viral panel sent within 48 hours of admission from January 2015 to December 2019. Patients who had a positive respiratory, urine, blood culture within 24 hours of admission were identified. Demographics, resource utilization, and outcomes were compared between the 2 groups. RESULTS: This study included 2192 patients. Of those, 269 patients had positive bacterial cultures. Out of these cultures from 192 patients were identified as contaminants. True bacterial coinfection was 3.5% (77/2192). Almost 1/3 of admitted patients were prescribed empiric antimicrobials. Children with bacterial coinfection tended to be younger (median age 8.4 months vs 16.3 months, p < 0.01) and had higher proportion of prematurity (23.3% vs 12.1%, p < 0.01). Children with bacterial coinfection were more likely to require ICU admission (37.6% vs 23.9%, p < 0.01) and intubation (28.5% vs 5.3 %, p < 0.01). They had higher ICU (5.7 days vs 1.9 days, p < 0.01) and hospital length of stay (4.0 days vs 2.0 days, p < 0.01), higher mortality (2.6% vs 0.2%, p = 0.02), and a higher median cost of hospital care ($3774.44 vs $2424.49.90, p < 0.01). CONCLUSIONS: The rate of bacterial coinfection in hospitalized children with viral infections is very low, which contradicts the routine administration of empiric antimicrobials. Patients with coinfection require more hospital resources and have worse clinical outcomes.

SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients.

OBJECTIVE: As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care. DESIGN: A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database. SETTING: The medical ward and ICU of 67 participating hospitals. PATIENTS: Pediatric patients younger than 18 years hospitalized with SARS-CoV-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non-SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6-9.4; P < 0.01). CONCLUSIONS: This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals.

OBJECTIVES: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19). STUDY DESIGN: This was a retrospective study on 356 hospitalized patients with MIS-C from March 2020 to September 2021 (28 sites in the United States) in the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. The effect of IVIG and steroids initiated in the first 2 days of admission, alone or in combination, on LOS was analyzed. Adjustment for confounders was made by multivariable mixed regression with a random intercept for the site. RESULTS: The median age of the study population was 8.8 (Interquartile range (IQR) 4.0, 13) years. 247/356 (69%) patients required intensive care unit (ICU) admission during hospitalization. Overall hospital mortality was 2% (7/356). Of the total patients, 153 (43%) received IVIG and steroids, 33 (9%) received IVIG only, 43 (12%) received steroids only, and 127 (36%) received neither within 2 days of admission. After adjustment of confounders, only combination therapy showed a significant decrease of ICU LOS by 1.6 days compared to no therapy (exponentiated coefficient 0.71 [95% confidence interval 0.51, 0.97, p = 0.03]). No significant difference was observed in hospital LOS or the secondary outcome variable of the normalization of inflammatory mediators by Day 3. CONCLUSIONS: Combination therapy with IVIG and steroids initiated in the first 2 days of admission favorably impacts ICU but not the overall hospital LOS in children with MIS-C.

Gastrointestinal Manifestations in Hospitalized Children With Acute SARS-CoV-2 Infection and Multisystem Inflammatory Condition: An Analysis of the VIRUS COVID-19 Registry.

BACKGROUND: Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS: Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS: Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS: GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.

Risk Factors for Longer Pediatric Intensive Care Unit Length of Stay Among Children Who Required Escalation of Care Within 24 Hours of Admission.

OBJECTIVE: Children who require early escalation of care (EOC) to the pediatric intensive care unit (PICU) after floor admission have higher mortality and increased hospital length of stay (LOS) as compared with direct emergency department (ED) admissions. This study was designed to identify subgroups of patients within this cohort (EOC to PICU within 24 hours of hospital admission) who have worse outcomes (actual PICU LOS [aLOS] > predicted PICU LOS [pLOS]). METHODS: This was a retrospective single-center cohort study. Patients who required EOC to PICU from January 2015 to December 2019 within 24 hours of admission were included. Postoperative patients, missing cause of EOC, and mortality were excluded. Predicted LOS was calculated based on Pediatric Risk of Mortality scores. Patients with aLOS > pLOS (group A) were compared with patients with aLOS ≤ pLOS (group B). Multivariable logistic regression was performed to adjust for confounders. RESULTS: Of 587 patients transferred to PICU after hospital admission during the study period, 286 patients met the study criteria (group A, n = 69; group B, n = 217). The 2 groups were similar in age, race, the severity of illness, and ED vitals and therapies. A higher proportion of patients in group B had EOC ≤ 6 hours of admission (51.1% vs 36.2%, P = 0.03), and a higher proportion in group A required Mechanical ventilation (56% vs 34%, P = 0.01). On multivariable regression, patients who required EOC to PICU after 6 hours after admission (adjusted odds ratio, 2.27; 95% confidence interval [CI] 1.2, 4.0), p,<0.01) and patients admitted to the floor from referral hospitals (adjusted odds ratio, 1.8; 95% confidence interval, 1.0-3.2), P = 0.04) had higher risk of greater than PLOS. CONCLUSIONS: Among patients who required EOC to PICU, risk factors associated with aLOS > pLOS were patients who required EOC to PICU longer than 6 hours after admission to the hospital and patients admitted to the floor as a transfer from referral hospitals.

A Longer Route to the PICU Can Lead to a Longer Stay in the PICU: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Admission to the pediatric ICU versus general pediatric floor for patients is a significant triage decision for emergency department physicians. Escalation of care within 24 hours of hospital admission is considered as a quality metric for pediatric E.R. There exists, however, a lack of data to show that such escalation leads to a poor outcome. METHODS: A retrospective cohort study was conducted to compare outcomes of patients who required escalation of care within 24 hours of hospital admission to the pediatric ICU (cases) from 01/01 2015 to 02/28 2019 with those who were directly admitted from emergency department to the PICU (controls). A total of 327 cases were compared to 931 controls. Univariate and multivariable regression analysis was done to compare the length of stay and mortality data. RESULTS: Patients who required escalation of care were significantly younger (median age 1.9 years compared to 4.6 years for controls) and had lower severity of illness score (PIM 3). Cases had a much higher proportion of respiratory diagnosis. ICU length of stay, hospital length of stay and the direct cost was significantly higher for cases compared to controls. This difference persisted for all age groups and respiratory diagnosis. The cost of care, however, was only different for 1-5 years and >5 years age groups. The difference in ICU length of stay (Δ11.1%) and hospital length of stay (Δ7.8%) persisted on multivariate regression analysis after controlling for age, sex, PIM3 score, and diagnostic variables. There was no difference in mortality on the univariate or multivariate analysis between the 2 groups. CONCLUSIONS: Patients who required escalation of care within 24 hours of hospital admissions have more prolonged ICU and hospital stay and potentially increased cost of care. This measure should be considered while making patient disposition decisions in the emergency department.

Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry.

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN: Retrospective study. SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

Association of transcutaneous CO2 with respiratory support: a prospective double blind observational study in children with bronchiolitis and reactive airway disease.

The use of clinical scoring to assess for severity of respiratory distress and respiratory failure is challenging due to subjectivity and interrater variability. Transcutaneous Capnography (TcpCO2) can be used as an objective tool to assess a patient's ventilatory status. This study was designed to assess for any correlation of continuous monitoring of TcpCO2 with the respiratory clinical scores and deterioration in children admitted for acute respiratory distress. A prospective observational study over one year on children aged 2 weeks to 5 years admitted with acute respiratory distress or failure secondary to Bronchiolitis and Reactive airway disease was performed. Continuous TcpCO2 monitoring for upto 48 h was recorded. Investigators, bedside physicians, respiratory therapists, and nurses were blinded from the transcutaneous trends at the time of data collection. Total of 813 TcpCO2 measurements at standard intervals of 30 min were obtained on 38 subjects. Subjects with abnormal TcpCO2 (> 45 mmHg) were younger (6.9 ± 5.2 vs. 23.05 ± 17.7 months,) and were more likely to be on higher oxygen flow rate (0.52 L/min/kg vs 0.46 lier/min/kg, p = 0.004) and higher FiO2 (38.4 vs 33.6, p < 0.001 using heated high flow nasal cannula. No difference was found in bronchiolitis score or PEW score in subjects with normal and abnormal TcpCO2. A small but statistically significant increase in TcpCO2 was observed at the escalation of care. Even though odds of escalation of care are higher with abnormal TcpCO2 (OR 1.92), this difference did not reach statistical significance. pCO2 can provide additive information for non-invasive clinical monitoring of children requiring varying respiratory support; however, it does not provide predictive value for escalation or de-escalation of care.

Peripheral intravenous catheters in hospitalized patients: Practice, Dwell times, and factors impacting the dwell times: A single center retrospective study.

BACKGROUND: Despite being the most common hospital procedure, limited information is available on the peripheral intravenous (PIV) catheter insertion practices. This study was designed to evaluate the contemporary PIV insertion practice (all age groups), and to identify the patient and device-related factors influencing the dwell times (<18 years). METHODS: Single Center Retrospective study. Patients of all age groups admitted to the hospital for >4 midnights, from 01/2015 to 12/2019. Data extracted by automated EMR audits. Variables included patient demographics, number of PIVs inserted, PIV size, location, dwell time, and length of stay. Standard comparative analysis, including multivariable linear regression for dwell time performed for patients <18 years. RESULTS: A total of 44,198 (39,341 (89%) adults and 4857 (11%) children) PIVs on unique patients met study criteria, with mean duration of 2.8 ± 2.4 days in children and 2.6 ± 1.3 days in adults (p < 0.001). Pediatric PIV had more dwell time variation, with a higher proportion lasting <1-day and also >2 SD of the age-specific mean, compared to adults. Adults had significantly higher number of PIVs placed/week compared to children. The failure rate for PIV was 56% in children and 76% in adults (p < 0.001). 1 out of 5 adults required >5 PIV/admission. Forty-five percent of children requiring only one PIV versus 21.8% of seniors. Discharge department, body part, and PIV size were independently associated with the dwell duration in children. No PIV size, however, had an independent increase in dwell duration over the reference of the 24 Ga cannula in children. PIVs placed in ante cubital vein and upper arm had dwell duration 26% and 20% longer than PIVs placed in the hand. CONCLUSIONS: The failure rate of PIV is high, and patients are subjected to multiple insertions during hospitalization. Hospital unit, body part, and PIV size are associated with the dwell duration in children.